Effect of enclosing terpenoids-rich Boswellia Carterri ethyl acetate extract in binary cyclodextrin based oligomer nano-complex for improving its activity via counteracting ICAM-1, Ilβ4 and LTB4 pathways in respiratory distressed rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effect of enclosing terpenoids-rich Boswellia Carterri ethyl acetate extract in binary cyclodextrin based oligomer nano-complex for improving its activity via counteracting ICAM-1, Ilβ4 and LTB4 pathways in respiratory distressed rats Bassant M.M. Ibrahim, Asmaa Badawy mohammed, Sally Abou Taleb, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3826210/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted 9 You are reading this latest preprint version Abstract Boswellia carterii (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethylacetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either B. Carterii plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in Nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within Nano sponges, the EE% of medicines varied between 98.52± 0.07 and 99.64± 1.40%. The nano sponges' particle sizes varied from 105.9±15.9 to 166.8±26.3 nm. Drugs released from Nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ4 levels and improved histopathologic profiles, when compared to the positive control group. Boswellia extract and its Nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder. Biological sciences/Biochemistry Biological sciences/Plant sciences Physical sciences/Nanoscience and technology Boswellia Carterri ethylacetate Nanosponges Drug Delivery Sustained release respiratory distress Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 1. Introduction Boswellia carterii , a member of the Burseraceae family, is widely distributed in Somalia and Ethiopia. Its bark contains secretory tissue that exudes a gum resin. This gum resin, known as olibanum, has been utilized as a medicinal substance in Unani (Islamic) and Chinese traditions for the treatment of various ailments including rheumatoid arthritis, osteoarthritis, dysmenorrhea, ulcers, swelling, and pain resulting from injuries [ 1 ]. Previous studies examining the phytochemical and pharmacological properties of olibanum have demonstrated its diverse biological activities, such as anti-inflammatory effects [ 2 ], cytotoxic properties [ 3 ], neuroprotective properties [ 4 ], α-Glucosidase inhibition [ 10 ], and antioxidant activity. Traditional Chinese medicine (TCM) has also employed olibanum to alleviate symptoms associated with traumatic injuries, chest congestion, pain [ 5 ], and inflammatory diseases like rheumatoid arthritis. The resin of BC is widely recognized as a rich source of structurally diverse diterpenoids, with the major classes being triterpenes (such as boswellic acids), oleanane-type compounds, cembrane-type compounds, ursane-type compounds, tirucallane-type compounds, and oxygenated macrocyclic diterpenoid-type compounds. Additionally, prenylaromadendrane-type diterpenes have also been identified in this resin [ 6 ]. Materials that are inhaled in the form of powder target the lungs, an inhaled pneumo-toxicant cause’s serious pulmonary damage via lipid peroxidation and even DNA breakdown [ 7 , 8 ]. Workers subjected to chronic talc powder inhalation are more susibtiple to silicosis and asbestosis, manifested by continuous cough and progressing dyspnoea. If the condition is left untreated, it will progress to pulmonary hypertension and fibrosis [ 9 ]. Pulmonary talcosis occurs as a complication of inspiration of large amounts of talc powder [ 10 ]. Lung injuries as pneumonia, pleurisy, fibrosis, and haemorrhage were evidenced in rat’s lungs of rats that were subjected to talc powder inhalation. Addiction of talc-adulterated marijuana and prolonged inspiration of talc powder by quarry laborers, lead to talc pneumoconiosis, bronchiolar obstruction and bronchiolitis, and may be fatal [ 11 ]. One kind of corticosteroid medicines that has been widely used as an anti-asthmatic agent is DEX [ 12 , 13 ]. DEX is an immunosuppressant with anti-inflammatory properties that can relieve the inflammation and pathophysiology of asthma [ 14 ]. Regrettably, the administration of oral corticosteroids over an extended period of time has been marred by the occurrence of systemic adverse reactions, such as renal insufficiency, hypotension, reduced body mass, conjunctival inflammation, and visual impairment, notwithstanding the drug's profound curative potency [ 15 ]. In view of this, there is a growing necessity to formulate a strategy to optimize the curative capabilities of corticosteroids while alleviating their systemic adverse effects [ 16 ]. The utilization of a pulmonary route for drug delivery is extremely attractive and has gained significant attention for the treatment of respiratory diseases and conditions. This is primarily due to the lung's expansive surface area, its rich blood supply, and its ability to effectively absorb medications for both local and systemic distribution [ 17 – 19 ]. In comparison to more conventional methods of drug delivery such as oral, peritoneal, and systemic administration, pulmonary medication delivery offers distinct advantages. By directly targeting the airway, this form of administration bypasses the first pass effect and allows for the precise treatment of pulmonary conditions. Consequently, medications delivered via the pulmonary route can elicit therapeutic effects at lower concentrations compared to alternative routes, thereby minimizing systemic side effects. However, it has been argued that a significant portion of inhaled corticosteroids remains within the oral cavity and permeates into the surrounding tissue, resulting in adverse effects [ 19 ]. In order to overcome these challenges in pulmonary medication delivery, the use of drug carriers that effectively transport pharmaceuticals to the desired site while maintaining appropriate drug concentrations within the airway is of utmost importance [ 20 ]. A considerable amount of effort has been devoted to the design of colloidal drug delivery systems in order to enhance the therapeutic effectiveness of drugs by modifying their bio-distribution and pharmacokinetics [ 13 ]. Liposomes, solid lipid nanoparticles, and polymeric nanoparticles have all undergone extensive investigation for drug delivery in the lungs. One of the innovative drug carriers that have recorded an enhanced effect is Nanosponges. Chemically crosslinked polymers known as Nanosponges are produced by reacting the CD unit with an appropriate crosslinking agent, such as CA, BDE, PMDA, CDI, or DPC [ 21 ]. βCD-NS has an amazing ability to encapsulate. They create novel drug carriers, safeguard biodegradable materials, enhance the aqueous solubility of weakly water-soluble compounds, or provide long-lasting delivery systems. Parenteral, pulmonary, and oral routes can all be impacted by the spherical form and tiny size of NS [ 22 , 23 ]. The goal of this work is to prepare and evaluate ethylacetate extract from Boswellia carterri and then Nano-sponge formulations loaded with DEX salt compared to Boswellia carterri extract Nano-sponge for pulmonary administration intended for the treatment of respiratory allergies and asthma to enhance their efficacy, avoiding hepatic first-pass metabolism as well as the severe side effects that accompany orally administered drugs such as gastric irritation, and, moreover, to overcome compliance problems, thus providing better convenience of treatment. 2. Materials and methods 2.1. Materials BC resins were gathered from the governorate of Khartoum in Sudan, where this collection was conducted in accordance with both local and national guidelines, as proper permission had been obtained for the collection of plant material. Dexamethasone Sodium Phosphate was graciously provided as a gift from the esteemed AMRIYA Pharmaceutical Industry Company in Egypt. Hydroxypropyl β-cyclodextrin (HPβ-CD) (KLEPTOSE HPB, MW 1380) and epichlorohydrin-β-cyclodextrin (EPI-β-CD) were kindly supplied by the reputable company Roquette in France. Diphenyl carbonate (DPC) was procured from the esteemed establishment Acros Organics in Belgium. Prednisolone was obtained from the well-known Sigma Chemical Co. (St Louis, MO, U.S.A.). Disodium hydrogen phosphate anhydrous and Potassium dihydrogen phosphate were purchased from El-Gomhouria Pharmaceutical Chemicals in Egypt. The cellulose membrane was acquired from the esteemed company Sigma-Aldrich, chemie Gmbh, located in Steinheim, Germany. All other chemicals and solvents used are of chemical grade and were utilized without any additional purification. Talc powder for induction of respiratory distress, was purchased from local medical suppliers; brand name “Five Fives Baby Mary Talcum”, it is high quality fragrance and clumps free powder, each powder pack weighs 200 gm. Diethyl ether and Formaldehyde were purchased from “Sigma Chemical Co., St. Louis, MO, USA”, the former for induction of anaesthesia before withdrawal of blood and the later for fixation of postmortem tissues. Diagnostic Elisa kits: “Intracellular adhesion molecule 1(ICAM-1-1), Leukotriene B4 (LTB 4), Interleukinβ 4 (ILβ4)”, for assessment of allergic and inflammatory markers levels in serum were purchased from “Elabscience Inc (USA)”, their measurement procedures followed the manufacturer’s guidelines. Trolox from Sigma Aldrich, all other chemicals and solvents were of high analytical grade. Animals In the present study, female Wister albino rats were used. Fifty animals of body weights (150–175 g) were obtained from the animal house colony of National research center in Egypt. They were housed in metal cages of uniform weights and designs, in well aeriated room at temperature range 22 ± 3˚C, and humidity range 55 ± 5%. Standard chow and free water access were available. The study was done in accordance with the guide for care and use of laboratory animals Approval of the ethics committee of “National Research Centre” numbered 19/209 was obtained prior to performance of the study[ 24 ]. The experiments were consistent with the civil regulations of “Animal Welfare and the Institutional Animal Ethical Committee (IAEC)”, and were congruent with the “Animal Research: Reporting of In vivo Experiments (ARRIVE)” guidelines[ 25 ]. 2.2. Methods 2.2.1. Phytochemisty Section 2.2.1.1. Plant materials and Extraction Boswellia carterii was acquired from the city of Khartoum, located in the Republic of Sudan. The desiccated resin, weighing 500 grams, underwent a comprehensive extraction process using 3 liters of methanol at ambient temperature, repeated thrice. Subsequently, the extract was subjected to filtration and concentrated under reduced pressure at a temperature of 45°C, employing a rotary evaporator[ 26 ]. The resulting unrefined residue was immersed in water, allowing for an overnight duration, and underwent a sequential partitioning procedure involving chloroform, followed by ethyl acetate, n-butanol, and ultimately, water[ 27 ]. 2.2.1.2. Phytochemicals screening of BC extracts were conducted to identify the presence of various compounds. The methanolic, dichloromethane, ethylacetate, butanol and water extracts were examined for the presence of carbohydrates and/or glycosides using the a-naphthol sulphuric acid reagent, as previously described by Lewis and Smith[ 28 ]. Tannins were detected using the method developed by Shellard [ 29 ]. To test for alkaloids, one mL of the alcoholic extract filtrate was mixed with 2 mL of Dragendoff's reagent [ 30 ]. The presence of alkaloids was indicated by the formation of a turbid orange color. Mayer's reagent was used as a confirmation test for alkaloids, and the appearance of a yellow precipitate confirmed their presence [ 31 ]. The potential presence of flavonoids was determined by the formation of a yellow color according to Trease and Evans [ 32 ]. Additionally, the extracts were treated with magnesium / HCl, and the formation of a red color indicated the possible presence of flavanones and/or flavonol [ 33 ]. Saponins were identified if a froth persisted for approximately 30 minutes[ 29 ]. Lastly, a green coloration in the upper layer and a deep red color in the lower layer indicated the presence of steroids and triterpenoids, respectively, as reported by Hanson [ 34 ]. 2.2.1.3. Metabolomics of secondary metabolites from BC resins using LC/MS/MS. 10 mg of two extract were dissolved in 1 ml of 80% concentration methanol and then filtrated by a sarangi filter. The diluted extract was repeated three times. The UPLC system (specifically the Acquity system from Waters, located in Milford, USA) was connected to the Q-Exactive hybrid MS/MS quadrupole - Orbitrap mass spectrometer (manufactured by Thermo in Germany). To achieve chromatographic separation in this system, a water solution acidified with 0.1% formic acid (referred to as solvent A) and acetonitrile (referred to as solvent B) were used, with a mobile phase flow rate of 0.3 mL/min. The gradient for the separation process was as follows: from 0 to 7 minutes, the composition changed from 50% solvent A to 50% solvent B, and from 7 to 15 minutes, it transitioned to 98% solvent B. These conditions were maintained for a total of 17 minutes. The separation was performed using the BEH shield C18 column, which had dimensions of 150×2.1 mm and 1.7 µm particle sizes. The Q-Exactive MS was operated with the following settings by Piasecka et al., [ 35 ]. 2.2.1.4. Processing Data We have developed a methodology for determining the fragmentation patterns of 49 metabolites using mass spectrometry. This comprehensive approach includes information on retention time and MS/MS data. The raw MS data for the two fractions (methanol and ethylacetate) of BC metabolites were exported in a standardized output format (abf) and analyzed using MS-DIAL 4.18, a software tool that offers improved and standardized untargeted metabolomics data analysis. To eliminate noisy spectra, the MSP format was employed along with a classical spectral similarity calculation. The potential metabolites of interest were identified by comparing their fragmentation patterns and RI with those found in the Reaxys, KNAPSACK, and RIKEN databases. [ 36 ]. 2.2.2. Nano-section 2.2.2. 1. Preparation of Nano sponges A modified version of the ultrasound-assisted synthesis approach was employed to synthesize NSs. Diphenyl carbonate, employed as a cross-linker, and HPβ-CD, utilized as a polymer, was combined in distilled water at a predetermined molar ratio [ 37 , 38 ]. Table 4 shows the ratios of HPβ-CD: DPC that were employed (1:5, 3:1, 4:1, and 5:1). At 90°C, the mixture was sonicated, and then homogenized in a hot water bath for seven minutes at 12,000 rpm. After being moved to falcon tubes, the mixture was centrifuged for 30 minutes at 6000 rpm. Following centrifugation, the medication was added, and the mixture was shaken at 150 rpm for the whole night. The mixture was centrifuged at 6000 for 30 minutes at room temperature after being sonicated at 90 o C the next day. After transferring the mixture to a petri dish and adjusting the volume for freeze drying, it was kept at 25ºC until needed again. This process will yield spherical, uniformly sized nano sponges. 2.2.2.2. Determination of Encapsulation efficiency (EE%) The samples underwent filtration by means of a 0.22 µm membrane filter and were subsequently subjected to analysis at the predetermined λ max , specifically at 242 nm [ 39 ], utilizing an ultraviolet-visible (UV) spectrophotometer (Pharma spec 1700, Shimadzu, Japan). The estimation of encapsulation efficiency for all ratios was conducted through the utilization of the subsequent equation: EE% = (M act / M the ) X 100 Where M act = actual DEX content in weighed quantity of Nano sponges, and M the = theoretical DEX content in Nanosponges [ 40 ]. 2.2.2.3. Vesicle size, polydispersity index and Zeta Potential Measurement The samples distributed in double-distilled water were subjected to examination of PS, ZP, and PDI using Zeta-sizer (Nano Series ZS90, Malvern Instruments Ltd., Worcestershire, UK) and dynamic light scattering (DLS)[ 41 ]. 2.2.2.4. Preparation of the Optimized formulations: Following the completion of earlier trials, the ideal molar ratio for generating DEX salt NSs with the best EE%, PS, and ZP values was chosen to be the optimum formulation. Then, BC plant extract NSs (P1) were prepared using the chosen molar ratio of HPβ-CD: DPC. In the meantime, a novel complex containing HPB-CD and epichlorohydrin-β-cyclodextrin (EPI-β-CD) was created at the chosen molar ratio, and it was loaded with plant extract (P2) and Dex salt (D5) as shown in Table 4 . The new formulations were prepared using the same procedure that was described in section 2.2.5. 2.2.2.5. Determination of EE%, PS, ZP and PDI of the optimized formulations: As stated in section (2.2.6), the resulting DEX salt and plant formulation's EE% was measured at predetermined λ max 242 and 252 nm respectively. Table (4) displays the composition, encapsulation efficiency, and physico-chemical parameters of the optimized formulations. 2.2.2.6. Characterization of the optimized formulations 2.2.2.6.1. Surface Morphology Transmission Electron Microscopy (TEM) The selected formulations' morphological features were analyzed through the use of TEM (JEOL Co., JEM-2100, Japan). After applying one drop of the diluted sample to a carbon-coated copper grid, the samples were stained after the grid had dried for fifteen minutes at room temperature. The grid was sprayed with a drop of 1%w/v phosphotungstic acid solution, allowed to stand for three minutes, and then placed under the microscope to examine the samples at the appropriate magnifications for surface characteristics and shape. Scanning Electron Microscopy (SEM) Using a scanning electron microscope (SEM) (Quanta FEG 250, ThermoFisher Scientific Co., Czech Republic), the surfaces of the chosen formulations were analyzed. Using double-sided tape, freeze-dried samples were attached to aluminum stubs and then coated with a thin layer of gold using a sputter coater unit. The SEM was run at a distance of 10 mm and an acceleration voltage of 20 kV. 2.2.2.6.2. Fourier transform infrared spectroscopy (FTIR)analysis. FT-IR analysis was used to identify any potential interactions between the blend of chosen formulations and the Nano sponge’s components. The infrared spectrum (400–4000 cm − 1 ) was used to scan the samples (JASCO 6100, Tokyo, Japan). Potassium bromide pellets were used to prepare the FT-IR samples. 2.2.2.7. In-vitro release Study In this investigation, release study of DEX and Plant NSs formulations (D1, D5, P1 and P2) as well as free DEX and Plant solutions was performed. The dialysis bags, specifically made of Dialysis tubing cellulose membrane obtained from Sigma-Aldrich Co., located in St. Louis, USA, with a molecular weight cut-off ranging from 12,000 to 14,000, were appropriately filled with a quantity equivalent to 2 mg of the NSs formulations alongside aqueous solutions of DEX and plant extract. Prior to being suspended in screw-capped glass containers with a capacity of 100 ml, which were also filled with 100 ml of PBS with a pH value of 7.4 in order to maintain sink condition, the dialysis bags were meticulously sealed on both ends to effectively prevent any leakage from occurring. It is worth noting that this procedure was done to ensure the integrity and accuracy of the results [ 42 , 43 ]. The entire experiment took place within a controlled environment, namely a thermostatic shaking water bath provided by Memmert, model SV 1422, which is a reputable brand based in Germany. The temperature was set at a constant 37°C with a tolerance of 0.5°C, while the shaking speed was maintained at 100 revolutions per minute. Throughout the course of the experiment, samples were regularly collected at specific time intervals and simultaneously replaced with an equal volume of the designated replacement release medium. This meticulous process was carried out to sustain the desired sink state and ensure the reliability of the findings. In order to compare the DEX and plant concentrations in the removed samples to blanks that had received the same treatment, spectrophotometric analysis was used. By dividing the amount of drug released by the amount of drug in the dialysis bag at the beginning, the cumulative release percentages were calculated. Three distinct samples were used for each measurement, which was done in triplicate. Numerous mathematical models, including Higuchi's square root of time model and zero and first order kinetic models, were used in the kinetic investigation of drug release from NSs formulations[ 44 ]. The plots of Q vs. t in the case of zero order, log (Q 0 - Q) vs. t for first order, and Q vs. t 1/2 for the Higuchi model were used to derive the R 2 values that indicate the coefficient of determination. Where (Q) is the amount of drug that has been released at time (t) and (Q 0 - Q) is the amount of drug that is still present at time (t). The most accurate model was considered to have the highest correlation coefficient values or determination coefficient (R 2 ). 2.2.3. Pharmacological section 2.2.3.1. In vitro study of DPPH and ABTS antioxidant activity The method employed to evaluate the in vitro antioxidant activity of two BC plant extracts was the DPPH and ABTS free radical-scavenging activity method. Different concentrations (70, 50, 30, 20, 10, 5, 2.5, 1.5, 1 and 0.5µg/mL) were utilized for this purpose. As a positive control, ascorbic acid and trolox were employed[ 45 ]. The estimation of ABTS + in various extracts was conducted using the methodologies outlined by Dinkova-Kostova et al. [ 46 ]. The DPPH (1,1-diphenyl-2-picrylhydrazyl, 250 mM) radical scavenging assay was carried out as described by Mohammed et al[ 47 ]. To calculate the percentage inhibition of the DPPH and ABTS + radicals, the following formula was utilized: % inhibition = [(A control - A sample )/A control ] x 100. In the case of DPPH, A represents the absorbance at 517 nm, while for ABTS+, A is the absorbance at 734 nm [ 48 ]. 2.2.3.2. In vivo Pharmacological study 2.2.3.2.1. Experimental design of the efficacy study Fifty female Wistar albino rats were used for evaluation of the efficacies of the Boswellia carterii extract, DEX salt and the tested formulations. The rats were divided into 10 equal groups (n = 5). Rats in group I acted as the negative control group and received oral saline solution 0.9%. The other nine groups were exposed to 50 mg/m 3 talc for 6 hours daily, 5 days/week for 4 weeks for induction of respiratory distress [ 49 ]. After 4 weeks of exposure to talc powder, they were subdivided into the following groups: group II which was untreated and served as positive control group, and treated groups III, IV, V, VI, VII, VIII, IX and X which received Dexa salt, D1, D5, Boswellia carterii plant extract, P1, P2, Drug-free NSs DF1,, Drug-free NSs DF2, respectively. All were given in doses of 10 µl which was equivalent to 20 µg of each substance. All were instilled in each nostril (IN) for 4 weeks following cessation of exposure to talc powder. Each rat was examined daily pre and post exposure to talc powder and during treatment to observe any symptoms of respiratory distress such as either apnoea or dyspnoea manifested by cyanosis around mouth, panting or lethargy. After the terminal treatment dose, the rats were fasted for about 16 hours before blood sampling for biochemical assay and dissection for histopathological examination [ 50 ]. 2.2.3.2.2. Blood sampling and biochemical estimation of Anti-inflammatory and anti-allergic biomarkers: Sixteen hours after last dose of treatment, all rats were anaesthetized and the “retro-orbital plexus of veins” was punctured for blood sampling. Then the samples were placed in the centrifuge and the rotating speed was set at 1500 rpm for duration of 10 min in order to get clear serum. Biochemical analysis was done by using “ELISA kits” following manufacturer’s guidelines for rat “ICAM-1-1, ILβ4 or leukotriene B4”. ELISA Tests Principles The ELISA kit employed the principle of "Sandwich-ELISA". The kits were equipped with micro ELISA plates that had already been coated with an antibody that specifically targeted either Rat ICAM-1, ILβ-4, or leukotriene B4. The micro ELISA plate wells were then subjected to the addition of standards or samples, which were subsequently combined with the specific antibody. Following this, a biotinylated detection antibody that specifically targeted either Rat ICAM-1-1, ILβ4, or leukotriene B4, as well as Avidin-Horseradish Peroxidase (HRP) conjugate, were added successively to each micro plate well and incubated. The removal of free components was achieved through a thorough washing process. Subsequently, the addition of the substrate solution to each well took place. It was observed that only the wells containing rat ICAM-1-1, ILβ4, or LTB4 displayed a blue coloration resulting from the presence of the biotinylated detection antibody and Avidin-HRP conjugate. The enzyme-substrate reaction was brought to a halt by the addition of the stop solution, leading to a yellow coloration. The spectrophotometer was employed to measure the optical density (OD) at a wavelength of 450 nm ± 2 nm. It was established that the OD value was directly proportional to the concentration of either Rat ICAM-1-1, ILβ4, or LT B4. The concentrations of rat serum ICAM-1-1, ILβ4, or LTB4 were determined by comparing the OD of the samples to the standard curve. 2.2.3.2.3. Tissue preparation for histopathological examination: All animals were sacrificed by euthanasia. All parts of the upper and lower respiratory tract from each animal were excised and fixed in 10% neutral formalin solution for 24 hours, followed by washing with tap water, dehydrating in alcohol, clearing in xylene and ultimately embedding in paraffin[ 51 ]. Serial sections of 3 µm thickness were cut followed by staining with hematoxylin and eosin [ 47 ], for preparation for histopathological examination. All images were captured at “The Pathology Lab in the National research Centre in Egypt” by using the image analysis system with a light microscope “Olympus CX41” and “SC100 video camera” that were attached to a computer system. All the photomicrographs that were taken at different magnifications were processed using “Adobe Photoshop version 8.0”. 2.2.3.4. Statistical analysis All values were expressed as means of the results of biochemical parameters plus or minus the standard error. Comparisons between all means were conducted using the One Way Analysis of Variance (ANOVA) followed by the Tukey Kramer's test for multiple comparisons. A significance level of P ≤ 0.001 was considered statistically significant. The eighth version of the Graph pad prism software was utilized to perform all the statistical tests [ 52 ]. 3. Results and discussions 3.1. Phytochemical screening of Boswellia Carterii and their fractions After defatted resin powder, 100% methanol (2L) was added and kept overnight on shaking 120 rpm. The solvent was evaporated by rotary evaporator at 40 o C till dryness. The crude residue was suspended in water, left for a duration of 24 hours, and subsequently divided into four portions using 0.8ml of chloroform, followed by 0.8ml of ethyl acetate, 0.8ml of n-butanol, and finally 0.8ml of water. The findings demonstrated the existence of flavonoids, carbohydrates, tannins, triterpenoids, steroids, alkaloids, and saponin. These substances were displayed in (Table 1 ). Flavonoids and saponin were detected in the ethyl acetate, butanol, and water extracts. These findings align with the outcomes reported by [ 53 ], who identified the presence of flavonoids, carbohydrates, saponins, tannins, phenol, coumarins, and triterpenes. However, carbohydrates and tannins were not present in the chloroform extract (Table 1 ) [ 39 ]. Table 1 Phytochemical screening of Boswellia carterii and their fractions. Groups Boswellia carterii resins Total CH 2 CL 2 EtOAc n-Butanol H 2 O Volatile Oils ++ ˉ ˉ ˉ Carbohydrate ++ - +++ +++ ++ Tannins ++ - +++ +++ + Flavonoids, NaOH ++ ++ +++ ++ + Flavonoids (Shinoda test) ++ ++ +++ ++ + Saponin +++ ++ +++ +++ + Sterol and / or triterpenes +++ - - - - Coumarins +++ ++ ++ + - Alkaloids + + + - - (++), (+) and (-) refer to high, low and absente amount respectively 3.2. UPLC-HRMS profiles of BC- resins by LC-MSMS . The metabolomics profiles of compounds examined by LC-MS/MS of Boswellia carterii (BC) were documented in Table 2 . This table includes a total of 49 compounds and is visually illustrated in (Fig. 1 ). Cembrane-type diterpenes, which are a diverse group of oxygenated macrocyclic diterpenoids composed of 14-membered rings, represent a prominent class of secondary metabolites predominantly found in the coral genera Sinularia , Sarcophyton , Lobophytum , Tabacoo , and Boswellia . Twenty-six diterpenoids, classified as sixteen cembrane-type diterpenoids boscartins and ten prenylaromadendrane-type diterpenoids boscartols, along with twenty known triterpenoids, belong to nine tirucallane-types, six ursane-type, three oleanane-type, and two lupane-type. Their structure elucidations were achieved by the LC-MSMS examination. Compounds listed in the table were found in total methanol and ethylacetate extract; these are compounds compared with the literature, compounds identified from the electronic databases as KNApSAcK databases, and compounds identified from MS_Dial. This paper deals with many of the literature searches listed in (Table 2 ). Table 2 metabolomics profiles of listed compounds by LC-MSMS. No RT Compounds Names/ SMILES Chemical formula Mass ∆ ppm PDA Extracts Ref. measured &calculated exact mass of [M + H] + measured &calculated exact mass of [M-H]- Total EtOAc Group A: Cembrane-type diterpenoids 3 6.30 Boscartins T O = C(/C([H]) = C1\[H])CC[C@@]([H])(O)[C@](CC2)(C)O[C@]2([H])[C@@]3(C)CC[C@@]1(O3)C(C)C C 19 H 30 O 4 323.2212, 323.2217 305.1740[C 18 H 25 O 4 ], 287.2006[C 19 H 27 O 2 ], 241.1590[C 17 H 21 O] 321.2116, 321.2060 199.1695[C 12 H 29 O 2 ] -1.6244 245 * [ 1 ] 4 6.59 Boscartin E O[C@H](/C = C1\C)C[C@](O2)(C)[C@@H]2C[C@]3(C(C)C)CC[C@](O3)(C)[C@H](O)CC1 = O C 20 H 32 O 5 353.2231, 353.2244 334.2079[C 20 H 30 O 4 ], 316.198[C 20 H 28 O 3 ], 181.0866[C 10 H1 3 O 3 ] 352.2176, 352.2166 333.2071[C 20 H 29 O 4 ], 307.1914[C 18 H 27 O 4 ] -3.8969/ 2.8182 245 * [ 54 ] 5 6.74 Boscartin J C/C(CC/C = C1/C) = C\C[C@]2(C(C)C)CC[C@](O2)(C)[C@H](O)C[C@@H]1O C 20 H34O 3 323.2563, 323.2581 305.2480[C 20 H 33 O 2 ], 287.2345[C 20 H 31 O] 321.2107, 321.2060 303.2893[C 18 H 39 O 3 ], 199.1694[C 12 H 29 O 2 ] -5.4270 238 277 * [ 55 ] 7 7.78 Incensole oxide CC(C)[C@@]12CC[C@](C)([C@@H](O)CC/C(C) = C/CC[C@](O3)(C)C3([H])C2)O1 C 20 H 34 O 3 323.2582, 323.2561 305.2461[C 20 H 33 O 2 ], 287.2353[C 20 H 31 O], 263.1628[C 16 H 23 O 3 ] 151.1118[C 10 H 15 O] 0.3318 245 * * [ 54 ] 8 8.29 Boscartin C CC(C)[C@@]12CC[C@](C)(C(O)CC/C(C) = C/C(O)C[C@]3(C)C(O3)([H])C2)O1 C 20 H 34 O 4 339.2531, 339.2530 303.2318[C 20 H 31 O 2 ], 285.2211[C 20 H 29 O], 151.1119[C 10 H 15 O] 337.2383, 337.2373 293.2118[C 18 H 29 O 3 ] 0.1937/ 2.8029 245 * [ 54 ] 10 8.34 Boscartins P [H][C@@]12C[C@@]3(CC[C@@](C)(O3)[C@]3([H])CC[C@@](C)(O)[C@]([H])(CC[C@@]1(C)O2)O3)C(C)C C 20 H 34 O 4 339.2526, 339.2529 321.2422[C 20 H 33 O 3 ], 303.2321[C 20 H 31 O 2 ], 285.2202[C 20 H 29 O], 251.1997[C 16 H 27 O 2 ] 151.1119[C 10 H 15 O] 337.2383, 337.2373 319.1923[C 19 H 27 O 4 ], -1.2456/ 2.8029 245, 277 * [ 1 ] 11 8.79 Boscartins Q [H][C@@]12C[C@@]3(CC[C@@](C)(O3)[C@H](CC\C(C) = C\[C@@H](O)C[C@@]1(C)O2)OC(C) = O)C(C)C C 22 H 36 O 5 381.2488, 381.2499 303.2324[C 20 H 31 O 2 ], 137.0964[C 9 H 13 O] 379.2495, 379.2479 347.1853[C 20 H 27 O 5 ], 245.1551[C 16 H 21 O 2 ] 4.1676 245 * [ 1 ] 12 8.90 Boscartins X CC(C)[C@@]12CC[C@@](C)(O1)[C@H](CC\C(C) = C\CCC(= C)[C@H](O)C2)OC(C) = O C 22 H 36 O 4 363.2373, 363.2373 317.2119[C 20 H 29 O 3 ], 273.1853[C 18 H 25 O 2 ] -0.1711 245 * [ 1 ] 13 9.02 Boscartins AA CC(C)[C@@]12CC[C@@](C)(O1)[C@H](CC[C@](C)(O)\C = C\C(= O)\C(C) = C\C2)OC(C) = O C 22 H 34 O 5 379.2458, 379.2479 361.2358[C 22 H 33 O 4 ], 319.2269[C 20 H 31 O 3 ], 301.2162[C 20 H 29 O 2 ], 215.1432[C 15 H 19 O] 377.2334, 377.2323 315.2322[C 21 H 31 O 2 ], -5.6495/ 2.9619 245 * [ 1 ] 16 9.20 Boscartins Z CC(C)[C@@]12CC[C@@](C)(O1)[C@H](CC[C@@](C)(O)\C = C\C(= O)\C(C) = C\C2)OC(C) = O C 22 H 34 O 5 379.2480, 379.2479 319.2285[C 20 H 31 O 3 ], 301.2159[C 20 H 29 O 2 ], 243.1738[C 17 H 23 O] 215.1429[C 15 H 19 O] 377.2331, 377.233 333.2444[C 21 H 33 O 3 ], 265.1505[C 15 H 21 O 4 ] 0.1442/ 2.2338 245 * [ 1 ] 19 9.35 Boscartin D CC(C)[C@@]12CC[C@](C)(C(O)CC/C(C = O) = C/CC[C@]3(C)C(O3)([H])C2)O1 C 20 H 32 O 4 337.2377, 337.2373 319.2261[C 20 H 31 O 3 ], 301.2160[C 20 H 29 O 2 ], 283.2061[C 20 H 27 O] 0.9931 245 * [ 54 ] 21 9.65 (rel)-(1S,5R,7E,11E)-1-isopropyl-8,12-dimethyl-4- methylenecyclotetradeca-7,11-diene-1,5-diol CC(C)[C@]1(O)CC\C(C) = C\CC\C(C) = C\C[C@@H](O)C(= C)CC1 C 20 H 34 O 2 306.2546, 306.2553 288.2398[C 20 H 32 O] -2.2633 245, 274 * * [ 56 ] 22 9.85 Boscartin B CC(C)[C@@]12CC[C@](C)([C@]3([H])CC[C@](O3)(C)C(O)CC4(O[C@@]4(C)C(O)C2)[H])O1 C 20 H 34 O 5 355.2473, 355.2479 337.2370[C 20 H 33 O 4 ], 319.2267[C 20 H 31 O 3 ], 301.2146[C 20 H 29 O 2 ] 353.2334, 353.2323 335.2221[C 20 H 31 O 4 ] 309.2431[C 19 H 33 O 3 ], 141.0907[C8H13O2] 3.1631/-1.7360 245 * * [ 54 ] 23 9.98 boscartin A O[C@H]1[C@](O2)(C)CC[C@]2([H])/C(C) = C\C[C@@H](O)[C@](O3)(C)CC[C@]3(C(C)C)C1 C 20 H 34 O 4 339.2519, 339.2530 321.2425[C 20 H 33 O 3 ], 303.2314[C 20 H 31 O 2 ], 285.2217[C 20 H 29 O], 151.1119[C 10 H 15 O] 337.2283, 337.2373 251.1654[C 12 H 23 O 3 ], 139.0751[C 8 H 11 O 2 ] 2.8029 245, 306/ 249 * * [ 54 ] 30 10.92 (1S,3E,7E,11S,12R)-1-isopropyl-4,8,12- trimethyl-11-hydroxyl-15-oxabicyclo[10.2.1] pentadeca-3,7-dien-9-one CC(C)[C@@]12CC[C@@](C)(O1)[C@@H](O)CC(= O)\C(C) = C\CC\C(C) = C\C2 C 30 H 32 O 2 321.2419, 321.2424 289.2521[C 20 H 33 O] -1.7731 245 * [ 57 ] 42 13.38 Incensole CC(C)[C@@]12CC[C@](C)([C@@H](O)CC/C(C) = C/CC/C(C) = C/C2)O1 C 30 H 34 O 2 307.2643, 307.2632 289.2521[C 20 H 33 O] 3.8612 252 * * [ 58 ] 43 13.49 Incensol Acetate CC([C@]12CC[C@](O2)(C)[C@H](CC/C(C) = C/CC/C(C) = C/C1)OC(C) = O)C C 22 H 36 O 3 349.2732, 349.2737 289.2520[C 20 H 33 O] -1.5995 252 * * [ 58 ] Group B: Prenylaromadendrane-type diterpenoids 6 6.79 Boscartol M [H][C@@]12C(CCC(= C)[C@]3([H])CC[C@](C)(O)[C@@]13[H])[C@]2(C)C(O)\C = C\C(C) = O C 19 H 28 O 3 305.2107, 305.2111 287.2002[C 19 H 27 O 2 ], 269.1889[C 19 H 25 O] 303.1996, 303.1955 285.0402[C 19 H 25 O 2 ] -1.3020 245 * [ 55 ] 9 8.25 Boscartol K [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)C3[C@]1([H])C2(C)[C@H](O)C1OC(= O)C(C) = C1 C 20 H 28 O 4 333.2046, 333.2060 315.1955[C 20 H 27 O 3 ], 297.1836[C 20 H 25 O 2 ] 331.1914, 331.1904 313.1810[C 20 H 25 O 3 ] -4.3398/ 3.0811 245 * [ 55 ] 14 9.13 Boscartol P [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)CC\C = C(\C)COC(C) = O C 22 H 34 O 3 347.2581, 347.2581 311.2367[C 22 H 31 O], 243.2315[C 15 H 31 O 2 ] 0.000 245 * [ 59 ] 17 9.29 Boscarterol A [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)C3C1[C@@]2(C)\C = C\C = C(\C)CO C 20 H 30 O 2 303.2318, 303.2319 285.2214[C 20 H 29 O], 245.1908[C 17 H 25 O] 299.2017, 299.2006 [M-2H] 285.2899[C 20 H 29 O], -0.0484/ 3.8923 245 * [ 60 ] 20 9.46 Boscarterol F [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)\C = C\C = C(\C)C = O C 20 H 28 O 2 300.2085, 300.2084 282.1932[C 20 H 26 O] -0.3331 249 * [ 55 ] 29 10.64 Boscarterol G [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)C3[C@]1([H])[C@@]2(C)[C@@]1([H])[C@H](O)C = C(C)C1 = O C 20 H 28 O 3 315.1962, 315.1955 297.2377[C 18 H 33 O 3 ], 271.2072[C 19 H 27 O] 2.3034 * * [ 60 ] 37 12.87 Olibanumol D C 20 H 30 O 286.2293, 286.2292 268.2136, 258.2307 -0.6987 251 * * [ 61 ] 45 13.74 Boscartol A [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)C = CC = C(C)CO C 20 H 30 O 2 303.2312, 303.2319 285.2215[C 20 H 29 O] -2.2626 252 * [ 60 ] 46 13.76 Boscartol C [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)CC = CC(C)(C)O C 20 H 32 O 2 305.2476, 305.2475 287.2359[C 20 H 31 O] 0.1697 252 * [ 60 ] 47 13.80 Boscartol G [H][C@@]12CCC(= C)[C@]3([H])CC[C@](C)(O)C3[C@]1([H])[C@@]2(C)[C@@]1([H])[C@H](O)C = C(C)C1 = O C 20 H 28 O 3 317.2112, 317.2111 299.2011[C 20 H 27 O 2 ], 281.1895[C 20 H 25 O] 315.1965, 315.1955 297.2439[C 18 H 33 O 3 ], 271.2071[C 19 H 27 O] 0.3827/ 3.3693 252 * [ 60 ] Group C: Polyphenolics and derivatives 1 2.16 Quinic acid C 7 H 12 O 6 191.0552, 191.0550 173.0440[C 7 H 9 O 5 ], 85.0279[C 4 H 5 O 2 ] 0.9239 220 * * Ms-Dial 2 2.72 Gallic acid C 7 H 6 O 5 171.0289, 171.0288 153.0184[C 7 H 5 O 4 ], 127.0393[C 6 H 7 O 3 ] 169.0131, 169.0131 125.0229[C 6 H 5 O 3 ], 59.0122[C 2 H 3 O 2 ] -0.1609/ 0.3190 202,241, 267 Ms-Dial 15 9.14 Fisetin C 15 H 10 O 6 285.0403, 285.0394 171.1019[C 9 H 15 O 3 ], 151.0024[C 7 H 3 O 4 ], 127.1116[C 8 H 15 O] 3.4373 245 * Ms-Dial Group D: Triterpenes belong to tirucallane-type 24 9.97 Sacraoic acid C [H][C@@](CCC = C(C)C)(C(O) = O)[C@]1([H])CC[C@]2(C)C3 = C([C@@H](O)C[C@@]12C)[C@@]1(C)CC[C@@H](O)C(C)(C)[C@]1([H])CC3 = O C 30 H 46 O 5 487.3425, 487.3418 451.3221[C 30 H 43 O 3 ], 316.3476[C 30 H 44 O 2 ] 485.3280, 485.3262 441.3381[C 29 H 45 O 3 ] 383.2964[C 26 H 39 O 2 ] 3.8159 245, 306 * * [ 62 ] 25 10.17 Sacraoic acid D [H][C@@](CCC = C(C)C)(C(O) = O)[C@]1([H])CC[C@]2(C)C3 = C(C(= O)C[C@@]12C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@]1([H])CC3 = O C 30 H 44 O 5 485.3256, 485.3262 467.3158[C 30 H 43 O 4 ], 449.3051[C 30 H 41 O 3 ] 483.3117, 483.3105 439.3220[C 29 H 43 O 3 ], 381.2796[C 26 H 37 O 2 ] 3.1260/ -1.0887 245, 310 * * [ 62 ] 26 10.04 Spirosacraoic acid B [H][C@@](CCC = C(C)C)(C(O) = O)[C@]1([H])CC[C@]2(C)C(= O)[C@@]3(CC[C@@]12C)[C@H](O)C[C@]1([H])[C@]3(C)CCC(= O)C1(C)C C 30 H 46 O 5 487.4325, 487.3418 469.3294[C 30 H 45 O 4 ], 423.3261[C 29 H 43 O 2 ] 485.3275, 485.3262 467.3161[C 30 H 43 O 4 ], 441.3384[C 29 H 45 O 3 ], 340.2454[C 24 H 36 O] 1.4944/ 2.7470 245, 306 * * [ 62 ] 27 10.12 Boscartene L [H][C@@]1([C@@]2(CC[C@H](C(C)(O)C)OC2 = O)[H])CC[C@@]3(C4 = C([C@]5(CCC(C(C)([C@@]5(CC4 = O)[H])C) = O)C)CC[C@@]13C)C C 30 H 44 O 5 485.3261, 485.3262 467.3177[C 30 H 43 O 4 ], 451.3221[C 30 H 43 O 3 ] 421.3103[C 29 H 41 O 2 ] 483.3112, 483.3105 465.3025[C 30 H 41 O 4 ], 365.2841[C 26 H 37 O], 369.2425[C 24 H 33 O 3 ] 255.2324[C 16 H 31 O 2 ] -0.1455/ 1.4211 245, 277 * * [ 63 ] 28 10.35 Boscartene M [H][C@@]1([C@@]2(CC[C@H](C(C)(O)C)OC2 = O)[H])CC[C@@]3(C4 = C([C@]5(CCC(C(C)([C@@]5(CC4 = O)[H])C) = O)C)C(C[C@@]13C) = O)C C 30 H 42 O 6 499.3043, 499.3054 481.2960[C 30 H 41 O 5 ], 435.2896[C 29 H 39 O 3 ], 369.2424[C 24 H 33 O 3 ] 497.2912, 497.2898 453.3017[C 29 H 41 O 4 ], 401.2329[C 24 H 33 O 5 ], 301.1808[C 19 H 25 O 3 ] -2.3137/ 2.8208 245, 306 * * [ 63 ] 31 11.84 Boscartene N [H][C@]1(CC[C@@]2(C3 = C([C@]4(CCC(C(C)([C@@]4(CC3 = O)[H])C) = O)C)CC[C@@]12C)C)[C@@]5([H])CC(O[C@H]5/C = C(C)/C) = O C 30 H 42 O 4 467.3163, 467.3156 449.3051[C 30 H 41 O 3 ], 403.2992[C 29 H 39 O], 465.3006, 465.2999 450.2787[C 29 H 38 O 4 ], 406.2883[C 28 H 38 O 2 ], 369.2423[C 24 H 33 O 3 ] 1.6240/ 1.4881 249 * * [ 63 ] 34 12.09 Boscartene E [H][C@]1(C[C@@H](OC1 = O)C = C(C)C)[C@]1([H])CC[C@]2(C)C3 = C([C@@H](O)C[C@@]12C)[C@@]1(C)CCC(= O)C(C)(C)[C@]1([H])CC3 = O C 30 H 42 O 5 483.3108, 483.3105 437.3052[C 29 H 41 O 3 ], 419.2934[C 29 H 39 O] 481.2956, 481.2949 437.3065[C 29 H 41 O 3 ], 385.2383[C 24 H 33 O 4 ], 368.2357[C 24 H 32 O 3 ] -0.9783/ 1.5426 249 * [ 64 ] 35 12.31 Boscartene C [H][C@]1(CC[C@]2(C)C3 = CC[C@@]4([H])C(C)(C)C(= O)CC[C@]4(C)C3 = CC[C@@]12C)[C@]1([H])CC[C@@H](OC1 = O)C(C)(C)O C 30 H 44 O 4 469.3312, 469.3312 451.3221[C 30 H 43 O 3 ], 422.3123[C 29 H 42 O 2 ] 466.3163, 466.3156 [M-2H] 423.3271[C 29 H 43 O 2 ], 371.2592[C 24 H 35 O 3 ] 0.0031/ 1.6240 429 * * [ 64 ] 36 12.55 Boscartene B [H][C@]1(CC[C@]2(C)C3 = C(CC[C@@]12C)[C@@]1(C)CCC(= O)C(C)(C)[C@]1([H])CC3)[C@]1([H])CC[C@@H](OC1 = O)C(C)(C)O C 30 H 46 O 4 471.3471, 471.3469 453.3347[C 30 H 45 O 3 ], 407.3285[C 29 H 43 O] 468.3323, 468.3312 [M-2H] 451.3219[C 30 H 43 O 3 ], 407.3318[C 29 H 43 O], 371.2592[C 24 H 35 O 3 ] 0.4679/ 2.2139 249 * * [ 64 ] Group E: Pentacyclic triterpenes belong to ursane type 18 9.32 Madecassic acid O = C([C@]12CC[C@@H](C)[C@H](C)[C@@]1([H])C3 = CCC4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@]5([H])[C@H](O)C[C@@]4(C)[C@]3(C)CC2)O C 30 H 48 O 6 503.3385, 503.3367 485.3274[C 30 H 45 O 5 ], 459.3500[C 29 H 47 O 4 ], 401.3072[C 26 H 41 O 3 ] 3.5470 245 Reaxys 39 13.20 Olibanumol G O[C@@H]1C(C)(C)[C@]2(O)CC[C@@]3(C)[C@]4(C)CC[C@](CC[C@H]5C(C) = C)(C)[C@]5([H])C4CC[C@]3([H])[C@@]2(C)CC1 C 30 H 50 O 2 442.3782, 442.3805 424.3640[C 30 H 48 O] -5.2624 252 * [ 61 ] 41 13.36 β-Boswellic acid [H][C@@]12[C@@H](C)[C@H](C)CC[C@]1(C)CC[C@]1(C)C2 = CC[C@]2([H])[C@@]3(C)CC[C@@H](O)[C@](C)(C(O) = O)[C@]3([H])CC[C@@]12C C 30 H 48 O 3 457.3681, 457.3676 439.3214[C 29 H 43 O 3 ], 411.3228[C 28 H 43 O 2 ] 455.3527, 455.3520 409.3087[C 28 H 41 O 2 ] 1.1187/ 1.5808 256 * [ 65 ] 44 13.72 11-Keto-β-boswellic acid [H][C@@]12[C@@H](C)[C@H](C)CC[C@]1(C)CC[C@]1(C)C2 = CC(= O)[C@]2([H])[C@@]3(C)CC[C@@H](O)[C@](C)(C(O) = O)[C@]3([H])CC[C@@]12C C 30 H 46 O 4 471.3470, 471.3469 407.3328[C 29 H 43 O] 469.3320, 469.3312 407.3329[C 29 H 43 O] 0.3384/ 1.5636 252 * * [ 65 ] 49 14.91 Ursolic acid [H][C@@]12[C@@H](C)[C@H](C)CC[C@@]1(CC[C@]1(C)C2 = CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O) = O C 30 H 48 O 3 455.3532, 455.3520 311.1710 2.7202 256 * [ 66 ] 31 11.11 Asiatic acid O = C([C@]12CC[C@@H](C)[C@H](C)[C@@]1([H])C3 = CCC4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@]5([H])CC[C@@]4(C)[C@]3(C)CC2)O C 30 H 48 O 5 487.3430, 487.3418 469.3322[C 30 H 45 O 4 ], 373.2738[C 24 H 37 O 3 ] 2.4337 249 * * Ms-dial Group F: Triterpene belong to oleanane Type 32 11.44 Oleanolic acid [H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]1(C)C2 = CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O) = O C 30 H 48 O 3 457.3687, 457.3678 411.3257[C28H43O2] 1.7193 249 * Ms-dial KNApSAcK 33 11.95 Beta-Elemonic acid C/C(C) = C\CCC(C(O) = O)C1CCC2(C)C1(C)CCC3 = C2CCC4C3(C)CCC(C4(C)C) = O C 30 H 46 O 3 455.3542, 455.3520 437.3424[C 30 H 45 O 2 ], 419.33324[C 30 H 43 O] 453.3004, 453.2999 435.2917[ C29 H 39 O 3 ], 409.3105[C 28 H 41 O 2 ] 4.7978/ 0.9890 249 * [ 65 ] 40 13.23 Elemonic acid [H][C@@](CCC = C(C)C)(C(O) = O)[C@]1([H])CC[C@]2(C)C3 = C(CC[C@@]12C)[C@@]1(C)CCC(= O)C(C)(C)[C@]1([H])CC3 C 30 H 46 O 3 454.3445, 454.3441 436.3305[C 30 H 44 O 2 ], 408.3334[C 29 H 44 O] 452.3375, 452.3363 435.3270[C 30 H 43 O 2 ] 0.8731/ 2.6529 252 [ 65 ] 34 12.07 Maslinic acid [H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]1(C)C2 = CC[C@]2([H])[C@@]3(C)C[C@@H](O)[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O) = O C 30 H 48 O 4 471.3477, 471.3469 427.3571[C 29 H 47 O 2 ], 385.3084[C 26 H 41 O 2 ] 1.7628 * Ms-dial Group G: Triterpene belong to lupane type 37 12.69 3β,20-dihydroxylupane-28-oic acid [H][C@]12[C@@H](CC[C@@]1(CC[C@]1(C)[C@]2([H])CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O) = O)C(C)(C)O C 30 H 50 O 4 475.3786, 475.3782 457.3683[C 30 H 49 O 3 ], 411.3262[C 28 H 43 O 2 ] 335.2579[C 21 H 35 O 3 ] 473.3604, 473.3625 - -1.2927/ -4.4223 249 * [ 67 ] 38 12.91 Alphitolic acid [H][C@]12[C@@H](CC[C@@]1(CC[C@]1(C)[C@]2([H])CC[C@]2([H])[C@@]3(C)C[C@@H](O)[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O) = O)C(C) = C C 30 H 48 O 4 471.3480, 471.3469 407.3301[C 29 H 43 O] 2.4102 252 * * Ms-dial Group H: Fatty acids 48 13.81 Oleic acid, methyl ester C 19 H 36 O 2 295.2640, 295.2632 245.2508[C 15 H 33 O 8 ] 2.8812 252 * * Ms-dial The preliminary identification was made using the entire extract of BC and the ethyl acetate fraction. The letters signify the compounds that were compared with existing literature, the compounds that were identified using the KNApSAcK database, the compounds that were identified using MS_Dial, and the compounds that were identified using Metlin. Table 3 Anti-inflammatory effects of tentative identified compounds of BC-Resins. Class of groups Roles as Chronic Anti-inflammatory; Promoting effect / Inhibiting effect Refs Cembrane-type diterpenoids The production of TNF-α and IL-6 as well as the expression of iNOS, COX-2, and p-NF-κB are significantly hindered by this compound. Moreover, this compound has demonstrated a greater inhibitory potential against the inflammatory agent 5-lipoxygenase. [ 68 , 69 ] Prenylaromadendrane-type diterpenoids This group has shown powerful inhibitory effects on the production of NO. [ 55 ] Triterpenes belong to tirucallane, ursane , oleanane and lupane type Furthermore, these types possess the ability to prevent the production of leukotriene in neutrophilic granulocytes through the inhibition of 5-lipoxygenase. Furthermore, a few boswellic acids have the capacity to impede the growth of cancer cell lines, induce apoptosis, block topoisomerases, and inhibit elastase in leukocytes. [ 67 ] Polyphenolics and derivatives They exhibit inhibitory effects on phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), resulting in a decrease in the synthesis of prostaglandins (PGs) and leukotrienes (LTs), thereby exhibiting anti-inflammatory properties. [ 70 ] 3.3. Preparation of Nanosponges Nano sponges based on cyclodextrin have become more well-known recently because of their special qualities. These sponges especially improve the stability and apparent solubility of medications by creating inclusion complexes through the inner nanocavities of cyclodextrins and non-inclusion complexes through the gaps in the cross-linked polymeric network of the sponges. Cyclodextrin-based nanostructures (NSs) such as HPβ-CD can provide a promising class of cross-linked polymers with an amazing three-dimensional architecture consisting of hydrophilic and hydrophobic nanosized pores that can effectively encapsulate a wide range of drugs and improve the solubility of less soluble drugs[ 71 ]. In the present study, NSs were prepared by ultrasound assisted technique. This method produces NSs with spherical shape and uniform in size [ 72 ]. Table 3 shows the formulation components as well as the findings reached from the evaluation of the responses. DEX NSs was created in the current study utilizing HPβ-CD as the polymer and DPC as the crosslinker in varied ratios (1:5, 3:1, 4:1, and 5:1). NSs were effectively prepared in all of the formulations examined. Table 3 Composition, entrapment efficiency and physico-chemical properties of DEX NSs and the optimized NSs Formulation. Code Drug Molar Ratio EE% ± SD VS ± SD PDI ZP ± SD 2-Hydroxy propyl-β-cyclodextrin (2HP-β-CD) Polymerized-β-cyclodextrin (Epi-β-CD) Di-phenyl carbonate (DPC) D1 DEX 1 - 5 99.95 ± 1.60 166.8 ± 26.3 0.524 -27 ± 6.26 D2 DEX 3 - 1 98.52 ± 0.07 109.1 ± 32.4 0.612 -22.32 ± 1.15 D3 DEX 4 - 1 99.64 ± 1.40 105.9 ± 15.9 0.371 -20.53 ± 2.13 D4 DEX 5 - 1 99.23 ± 0.20 160.8 ± 24.3 0.604 -26.53 ± 3.79 D5 DEX 1 5 - 100%±6.24 74.04 ± 55.4 0.420 -29.92 ± 5.68 P1 EtoAc Extract 1 5 87.39%±1.99 244 ± 17.54 0.507 -25.4 ± 4.13 P2 EtoAc Extract 1 5 - 98.56%±2.88 359 ± 30.23 0.458 -28 ± 3.87 3.4. Encapsulation efficiency The EE% values for each DEX NSs formulation (D1–D4) are displayed in Table 3 . All formulations had EE% values between 98.52 ± 0.07 and 99.64 ± 1.40%. The success of DEX NS preparation was confirmed by the obvious high encapsulation efficiency (EE%) of all prepared NSs. The excellent crosslinking between HPβ-CD and DPC, which permits a large inclusion of DEX salt in the NSs matrix and cyclodextrin cavity, may be responsible for the high EE% of the generated NSs [ 73 , 74 ]. Along with the inclusion of DEX salt in the porous matrix of the Nano sponge, it is also responsible for entirely trapping the drug molecules as an inclusion complex inside the hydrophobic host cyclodextrins' cavities, which are surrounded by hydrophilic nanochannels [ 75 , 76 ]. 3.5. Vesicle size, polydispersity index and Zeta Potential The analysis of DEX NSs revealed that all produced NSs were in the nanosized range, with formulation sizes ranging from 105.9 ± 15.9 to 166.8 ± 26.3 nm (Table 3 ). It has been observed that formulations comprising a higher molar ratio of crosslinker exhibited PS greater than those comprising a lower molar ratio of crosslinker. This finding is in good agreement with previous reports [ 77 , 78 ], where the increase in crosslinker molar ratio resulted in a larger PS. Additionally, the data supported low polydispersity index (PDI) values of 0.371 to 0.612, which indicated a uniform and constrained vesicle size distribution [ 79 ]. Table 3 also shows that all of the formulations under investigation had a negatively charged zeta potential; this could be because of the free hydroxyl groups of βCD and 2-HPβCD, as well as the carbonyl groups of DPC [ 80 , 81 ]. All formulations under investigation had absolute ZP values more than 20, which are more than enough to maintain the individual particles' separation from one another by electrostatic repulsion. Thus, scattered particles are therefore physically stable. 3.6. Selection of the optimized DEX salt and ethylacetate plant extract NSs formulations: According to the results of EE%, PS, PDI and ZP, the best molar ratio between HPβ-CD and DPC was (1:5) (D1). The same molar ratio HPβ-CD: DPC (1:5), was used for the preparation of Plant extract NSs (P1) and the same molar ratio was used for the preparation of NSs using HPβ-CD and EPI-β-CD in the ratio of (1:5) and loading of DEX and ethylacetate extraction in the new formulations (D5 and P2). The λ max of the plant extract was found to be at 252nm. The EE%, PS, PDI and ZP of the new formulations were estimated and demonstrated in Table 3 . Results revealed that new formulations D5, P1 and P2 exhibited high EE% (87.39%±1.99 to 100 ± 6.24), with particle size in the nano size range, low PDI and suitable ZP value. It was noticed that there was non-significant difference (p ≥ 0.001) in EE% between D1 and D5 as use of EPI-β-CD instead of DPC doesn’t affect EE% of DEX salt, On the other hand the use of EPI-β-CD in the preparation of ethylacetate plant extract NSs lead to a significant increase (p ≤ 0.001) in EE%. Since few years, studies have been carried out toward the use of epichlorohydrin-β-cyclodextrin (EPI-β-CD) polymer for the preparation of Nano sponges [ 82 , 83 ], as this polymerized form of β-cyclodextrin remains within the cavity structure of β-CD providing capability of forming inclusion complexes with a variety of guest molecules which can lead to increase the loading capacity of NSs [ 84 ]. 3.7. Characterization of the optimized Formulations 3.7.1. Surface Morphology Transmission Electron Microscopy (TEM) Figure 2 (a) depicts the morphology of NSs. The NSs have been found to be round and uniform, with no drug crystals on the surface. According to the figures, the NSs created using the ultrasonic assisted process have a uniform size distribution, crystallinity, and a porous character [ 85 ]. Scanning Electron Microscopy (SEM) The SEM images of NSs were illustrated in Fig. 2 (b). SEM analysis of the prepared NSs revealed nano-sized spherical particles having multiple pores on their surface [ 86 ]. There was no residual crystals from the drugs indicating the complete encapsulation of drugs in the polymer [ 87 ]. 3.7.2. Fourier transform infrared spectroscopy analysis The interactions between pharmaceuticals and excipients were investigated by comparing the FTIR spectra of pure components with drug-loaded Nano sponges (D1, D5, P1 and P2) (Fig. 3 ). The FTIR spectra of HP-β-CD showed prominent absorption bands at 3415 cm − 1 (O-H stretching), 2929 cm − 1 (C-H stretching), 1645 cm − 1 (H-O-H bending), 1157 cm − 1 (C-O stretching), and 1031 cm − 1 (C-O-C stretching) [ 88 , 89 ]. FTIR spectrum bands for DPC revealed distinctive absorbance band at 1753 cm − 1 for carbonate bond [ 90 ]. Epichlorohydrin-β-cyclodextrin (EPI-β-CD) has distinctive peaks for epichlorohydrin at 1288.36, 1249.79, and 721.33 cm − 1 , respectively, as well as a CH 2 Cl wagging band and C-Cl stretching in its IR spectra. The OH, CH 2 , and C-O-C stretching vibrations, which are approximately 3452.34, 3411.84, 3271.05, 2933.53, and 1099.35 cm − 1 , respectively, confirm that cyclodextrin is present in the structure [ 91 ]. The FTIR spectra of DPC showed distinctive peaks at 1513, 1509, 1480, 1397, 1314, 1312, 1214, 1210, 1176 and 1120 cm − 1 that can be assigned to C = H bending vibrations. The molecule containing carbonyl group shows strong absorption band for C = O stretching vibrations at the region 1850 and 1550 cm − 1 [ 92 ]. DEX exhibited distinct absorbance bands at 1706, 1660, and 1616 cm − 1 , which were attributed to -C = O stretching vibrations connected to C3-cyclic and C20 carbonyl groups, as well as double bond context coupled to -C = O bonds. Furthermore, two more different absorption bands of 3468 cm − 1 and 1270 cm − 1 were realized due to the stretching ambiences of the O-H and C-F bonds, respectively [ 93 , 94 ]. The comparative nature of the IR spectrum of BC ethylacetate plant extract can be observed when compared to Boswellia acids. It is worth noting that the spectrum exhibits characteristic peaks at specific wavenumbers, namely 3437 cm − 1 (indicative of OH stretching), 2932 cm − 1 (associated with C-H stretching), 1697 cm − 1 (highlighting C = O stretching of aryl acid), 1453 cm − 1 (pertaining to C-H bending), 1375 cm − 1 (linked to COO symmetric stretching of carboxylates), 1240 cm − 1 (relating to C-CO-C stretching of aryl ketone), as well as 1025 cm − 1 and 988 cm − 1 (both associated with ring structures of cyclohexane) [ 95 ]. In the distinctive peaks of DEX or ethylacetate plant extract, the IR spectrum of the optimized Nano sponge formulations (D1, D5, P1 and P2) revealed a shifting and diminished intensity. This shift in the characteristic peaks may be explained by the presence of physical interactions between drugs and various NS elements, such as Van der Wall bonds, hydrogen bonds, or dipole interactions, without any chemical changes to the drugs' structure after encapsulation, which can result in the best possible entrapment of DEX or ethylacetate plant extract in Nano sponges [ 80 , 96 , 97 ]. 3.8. In- vitro Release Study: CD-based NSs can be a useful technique for delivering medications in a sustained manner. Drug encapsulation in a crosslinked NSs structure allows for prolonged drug administration, allowing for lower doses, less side effects, and changed pharmacokinetics. These characteristics can be used to improve medicine distribution [ 98 ] The prepared NSs formulations (D1, D5, P1 and P5) release profiles were shown in Fig. 4 . The tested formulations' release profiles displayed a biphasic behavior, with an initial quick release lasting for the first six hours. This first rapid release may have been caused by the drug's adsorption on the NSs surface vesicles, which led to a fast release from NSs [ 99 ]. Followed by a delayed, slow release for 24 hours. Frequent administration is the main disadvantage of the majority of the traditional, commercially available drug delivery devices. The medication, however, is kept and released gradually over time after being loaded into the Nano sponge. It has been previously reported that hydrophilic cyclodextrin Nano sponges are used to adjust the drug release rate, as it facilitates medication absorption over biological barriers and it may help to protect the medication throughout its passage through the stomach [ 100 , 101 ]. The correlation coefficient (R 2 ) values of NSs formulations demonstrated a superior fit to Higuchi's model compared to the zero order and first order kinetic models. This conclusion was drawn from a linear regression analysis of the mathematical models employed to analyze the release data obtained from the NSs formulations. The R 2 values ranged from 0.8752 to 0.9943. In instances where a high degree of linearity was observed, the Peppas equation was utilized to further investigate the release process of DEX and plant material [ 102 , 103 ]. According to the Peppas theory, if the value of n = 0.43, the drug release process adheres to Fickian diffusion. When 0.43 < n 0.85 indicates super-case II transport [ 102 ]. The range of values for the release exponent "n" in the NSs formulations varied from 0.213 to 0.452, thereby suggesting a release mechanism controlled by Fickian diffusion. 3.9. Pharmacological Study 3.9 .1. In vitro antioxidants activity of Boswellia Carterri extracts The effects of the time of interaction of several antioxidants on the suppression of the absorbance of the ABTS + radical cation at 734 nm for the standard reference compounds, trolox and ascorbic acid, are shown in Table (S1). The total extract, dichloromethane fraction, ethyl acetate fraction, butanol fraction, and water fraction values are compared with those of the two standards. Numerous studies have been conducted on the antioxidant properties of vitamin C, trolox, and natural resin extract compounds. Therefore, the purpose of this study is to determine the antioxidant activity of standard compounds generated from different resins with respect to their ability to scavenge DPPH and ABTS radicals. Hazardous free radicals in humans are stabilized in large part by the DPPH and ABTS radical scavenging tests. Table (S1) presents the effects of the duration of interaction of specific antioxidants on the suppression of the absorbance of the ABTS + radical cation at 734 nm for trolox, ascorbic acid, the standard reference compounds. The values of the two standards are compared with those of total extract, dichloromethane fraction, ethyl acetate fraction, butanol fraction, and water fraction. The antioxidant activity of natural resin extract substances and Vit C and Trolox has been extensively studied. As a result, this study aims to identify the antioxidant activity of standard substances derived from various resins in terms of their DPPH radical scavenging activity and ABTS radical scavenging activity. The DPPH and ABTS radical scavenging assays play a crucial role in stabilizing harmful free radicals in the human body by providing a redox-functioned proton ion for unstable free radicals. This is accomplished by utilizing the fact that unstable violet DPPH and ABTS free radicals convert into stable yellow DPPH free radicals through the acceptance of a hydrogen ion from antioxidants. In this particular study, the results of the antioxidant activities assessed through the DPPH assay reveal that the BC resin ethyl acetate extract exhibits the highest antioxidant activity in both methods (IC 50 0.5325 and 0.5527, respectively). It is followed by the butanol fraction as an agent (IC 50 0.932 and 0.6476, respectively) when compared to the other extract samples and standard VitC and Trolox (Tables S1 and S2 and Fig. 5 ). The two methodologies employed in this section to gauge the antioxidant activity mutually corroborated one another, as all fractions were taken into account. This implies that the examined extracts may possess comparable chemical groups, and their effects can be attributed to these groups [ 104 ]. In this regard, the identification and characterization of Cembrane-type diterpenoids, Prenylaromadendrane-type diterpenoids, Triterpenes belonging to tirucallane, ursane, oleanane, and lupane types, as well as polyphenolics, prove instrumental in the development of natural antioxidant substances derived from BC resins. 3.9.2. In vivo Pharmacological study In the present study, observation of the negative control rats didn’t reveal any abnormal respiratory sign as their nostrils appearances and nasal colours were normal as well as their attitudes towards the examiner and caregiver, these signs were confirmed with the measured biochemical parameters of allergy and inflammation as “ICAM-1, Ilβ4 and LTB 4 ”, that were estimated in their sera, and were significantly less than the positive control group (Table 4 ). Histopathological examination of the lungs of the same group showed that they were more like a well-organized sponge consisting of functional respiratory units alveoli, each alveolus shared its wall (inter-alveolar septum) with adjacent alveoli, they were average thickness, the bronchioles were lined by columnar epithelium supported by smooth muscle layer had normal appearance and the bronchial vessels had normal looking and average thickness. The tracheas were lined by ciliate pseudostratified columnar epithelium, resting upon ordinary connective tissue with incomplete rings of hyaline cartilage. The nasal cavities were lined by pseudostratified epithelial mucosa and submucosal regions were filled of blood vessels, mucin and serous secreting gland (Fig. 6) On the other hand, signs of severe induced respiratory distress in all the rats that were powdered with talc powder for 4 weeks, and then left untreated for another 4 weeks (positive control group), were manifested by decreased food consumption, avoidance, irritability, increased aggression towards the researcher and the care-giver, hair ruffling, increased nasal discharge, nasal oedema and discolouration, together with significant elevation of ICAM-1, Ilβ4 and LT B4, compared to the negative control group (Table 4 ). Talc powder causes dryness of the tracheobronchial mucosa and impairs its ciliary function, moreover, the adsorption of the surfactant to the magnesium silicate powder augments the lung injury, in addition to the pathological signs that include oedema, inflammation of the bronchial, epithelium,, diffuse infiltrates, and lung injury, that lead to acute respiratory distress syndrome [ 105 ]. This explains the histopathological findings that were obtained on examination of tissues excised from rats of the positive control group in our study, which revealed that lung tissues were massively infiltrated with inflammatory cells infiltrates with germinal formation and destruction of bronchial walls, also the alveolar walls were thickened due to infiltration by inflammatory cells. Examination of the tracheal tissue revealed severe destruction of the tracheal lining with inflammatory cells infiltrate of submucosal tissue, and destruction of tracheal cartilage. Moreover, nasal tissue examination revealed that the nasal cavity was lined by pseudostratified epithelium, mucosa and submucosa region filled of blood vessels, mucin and serous secreting gland (Fig. 6). Treatment with conventional DEX salt preparation didn’t improve either the biochemical parameters as shown in Table 4 or the histopathological picture in Fig. 7, when compared to the positive control group. On the contrary, it significantly elevated the ICAM-1 compared to positive control group. The same was for the group treated with D1; however, it has significantly lowered the Ilβ4 levels only, when compared to positive control group, without affecting the levels of ICAM-1 or LTB 4 , denoting that it exerted only an anti-inflammatory effect without any anti-allergic potential. The best effect of DEX salt treatment was obtained with D5, as it significantly lowered the ICAM-1 and Ilβ4, however it significantly elevated the LTB 4 levels in sera, which means that it has both anti-inflammatory and to some extent anti-allergic therapeutic potentials on respiratory tract allergies. The biochemical investigations were confirmed by histopathological examination of lung tissues excised from DEX salt treated group, as it was found that the lung tissues were mostly destructed by severe infiltration of inflammatory cells with focal areas of mucin; while, lungs of D1 and D5 treated groups showed infiltration of inflammatory cells with evidence of germinal formation and thickened alveolar walls. Tracheal tissue of DEX salt treated group, showed that the tracheal lining was destructed and rested upon connective tissue infiltrated by inflammatory cells and focal areas of mucin; on the other hand, tracheas of D1 and D5 treated groups have been improved. Nasal tissue revealed for all groups that the nasal cavity was lined by pseudostratified epithelium, mucosa and the submucosa region filled of blood vessels, mucin and serous secreting gland (Fig. 7). Treatment with Boswellia extract and its Nano sponge’s formulations (P1 and P2) improved significantly, but with different extents, all the biochemical parameters mentioned in Table 4 , when compared to both conventional DEX salt and positive control groups. Histopathological examination of lung tissues of Boswellia extract treated group revealed that the lung was more likely to be destructed by massive inflammatory cells infiltrates which also destructed the muscular walls of the bronchi, and totally invaded their lumens. Also the group treated with P1 formulation showed destructive bronchial architecture by inflammatory cells, and some had focal formation, the alveolar walls were infiltrated by inflammatory cells, the same picture was presented in the group treated with P2 formulation, which showed indentation of bronchial lining with evidence of intra-bronchial mucous with destruction of bronchial and alveolar walls due to inflammatory cells infiltration. Examination of tracheal tissues of Boswellia extract group and the group treated with P2 formulation revealed hyperplastic columnar epithelium with inflammatory cells infiltrates. Also the group treated with P1 formulation showed massively destructed tracheal lining as it was infiltrated by inflammatory cells. Nasal tissue examination revealed for Boswellia extract group and the group treated with P2 formulation showed disturbed mucosal region by edema and inflammatory cell infiltrate, this picture is improved in the group treated with P1 formulation as there are minimal inflammatory cell infiltrate with congested dilated blood vessels within mucosa and submucosal region (Fig. 8). Regarding treatment with Drug-free NSs (DF1 and DF2), they showed significant less levels of ICAM-1, when compared to conventional DEX salt group, but didn’t significantly show any difference in levels when compared to the positive control group; yet, it was significantly higher than Boswellia extract group level. The levels of Ilβ4 and LTB 4 in both groups were significantly less than positive control and conventional DEX salt groups, but higher than Boswellia extract group (Table 4 ). This indicates that drug-free nano-sponge have relative anti-allergic and anti-inflammatory effects but not limited to respiratory tract allergy only. Histopathological examination of lung tissues of the group treated with DF1 showed massively inflammatory cells infiltrates with destruction of bronchial walls; while, the group treated with DF2 showed more infiltration of inflammatory cells, with germinal formation also the alveolar walls were thickened due to infiltration by inflammatory cells. On the other hand, examination of tracheal tissue of the group treated with DF1, revealed more destruction of the tracheal lining with inflammatory cells infiltrate of submucosal tissue. The previous pathological picture showed improvement with minimal inflammatory cells infiltrate in the group treated with DF2. Nasal tissue examination of both groups showed that the nasal cavity was lined by pseudostratified epithelium, mucosa and submucosa region filled of blood vessels, mucin and serous secreting gland (Fig. 9). “Intercellular adhesion molecule 1 (ICAM-1)”, is a bispecific antibody that is extensively expressed on the respiratory epithelial cells of allergic patients [ 106 ]. ICAM-1 protein increases in airways of asthmatics [ 107 ]. Therefore, its level is a strong indicator of the effect of allergen and therapeutics, which target the respiratory system. Based on this fact, the results of the present study suggest that, the best effect obtained was that of Boswellia extract in Nano-sponge (P1), as it significantly lowered the ICAM-1 when compared to the positive control group and was near the normal level when compared to negative control group without significant difference, moreover it was significantly less than both conventional DEX salt and Boswellia extract levels. Leukotrienes LTB 4 is a lipid mediator that participates in the incidence of severe asthma or asthmatic exacerbations via acting as a potent neutrophil chemoattractant and via activation of CD 4 + T cells, eosinophils and macrophages. That’s why, its blockage is the target for respiratory allergies and asthma control [ 108 ]. Additionally, the cytokine “Interleukin 4 (ILβ-4)” plays a crucial role in induction and differentiation of T- helper cells. One of the major causes of asthma and inflammatory airway diseases are induced via ILβ-4 [ 109 ]. It was found in the present study that BC extract in Nano-sponge P1 also, lowered significantly both Ilβ4 and LTB 4 levels compared to both conventional DEX salt and positive control group. Table 4 Effects of treatment with Boswellia Carterii ethylacetate plant extract, Dexa salt and their Nano Sponge formulations on inflammatory and allergic mediators of respiratory tract Parameter Group ICAM-1 (pg/ml) Ilβ4 (pg/ml) LTB 4 (pg/ml) Negative control 351 ± 13.17 1490 ± 8.477 2660 ± 29.39 Positive control (untreated talcosis) 1323 ± 12.94 a 4604 ± 36.11 a 3973 ± 19.57 a Dexa salt 2652 ± 101.4 ab 4666 ± 88.82 a 4401 ± 85.77 a DEX NSs (D1) (20 µg) 1501 ± 8.197 abc 3715 ± 33.05 abc 3973 ± 60.05 a DEX NSs (D5) (20 µg) 400 ± 7.579 bc 3524 ± 16.12 abc 5168 ± 229 abc B. Carterii ethylacetate Plant extract 802 ± 13.56 abc 2309 ± 4.980 abc 2706 ± 43.58 bc B. Carterii NSs (P1) (20 µg) 343 ± 9.151 bcd 2566 ± 22.44 abcd 2658 ± 25.63 bc B. Carterii NSs (P2) (20 µg) 858 ± 17.61 abc 2847 ± 17.24 abcd 2190 ± 93.59 abcd DF1 NSs(20 µg) 1295 ± 15.61 acd 3550 ± 24.36 abcd 3610 ± 15.38 acd DF2 NSs(20 µg) 1303 ± 8.47 acd 2847 ± 17.24 abcd 3460 ± 17.86 abcd Results are expressed as means ± S.E, N = 5. Comparisons between means were carried out using one way analysis of variance (ANOVA) followed by Tukey Kramer’s multiple comparisons test. p ≤ 0.0001. (a) Significantly different from Negative control group (b) Significantly different from positive control group (c) Significantly different from Dexa salt group (d) Significantly different from Boswellia extract group Conclusion Successful extraction and characterization of the ethylacetate plant extract from B. carterii was achieved. The majority of the desirable characteristics necessary for an adequate dosage form were displayed by Nano sponges loaded with B. carterii ethylacetate plant extract or Dex salt. Small particle size Nano sponges have been created. Sustained release for up to 24 hours was achieved by the release profiles. Additionally, these Nano sponge formulas have been shown to have a sufficient capacity for extending the time of drug release, which may advantageously result in a reduction in the frequency of drug administration, a decrease in medication dosage, and the avoidance of relatively systemic unwanted adverse effects . The anti-inflammatory activity of either B. Carterii ethylacetate plant extract, Dexa salt and their Nano formulations (D1, D5, P1, and P2) in the treatments of respiratory allergies were evaluated . Histopathologic examinations and measurements of intracellular adhesion molecule-1 (ICAM-1), Leukotriene B 4 (LTB 4 ) and Interleukin β4 (ILβ4) levels revealed that the treatment significantly lowered the levels of the inflammatory biomarkers in treated rats and exhibited improved histopathologic profiles when compared to the positive control group. Boswellia ethylacetate extract and its Nano sponge formulation P1 had promising therapeutic effects on upper and lower respiratory diseases. The effect of boswellia ethylacetate extract formulation P1 may be due to synergism between both the extract and DF1. This effect was achieved by blocking both the ICAM-1 and LTB4 pathways, therefore counteracting the allergic and inflammatory effects of talc powder. Abbreviations Abbreviation Meaning BC Boswellia carterii CID Collision-Induced Dissociation HESI Heated Electrospray Ionization C + ve Positive control group DPPH 2,2-diphenyl-1-picrylhydrazyl DEX Dexamethasone salt ICAM-1 Intracellular adhesion molecule-1 Ilβ4 Interleukinβ 4 LTB 4 Leukotriene B4 CD cyclodextrin CA citric acid ABTS 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) PMDA pyromellitic dianhydride CDI 1, 1′-Carbonyldiimidazole DPC diphenyl carbonate LCMSMS Liquid chromatography–mass spectrometry HPβ-CD hydroxypropyl β-cyclodextrin abf common output format RPM Rotations per minute IAEC Institutional Animal Ethical Committee UPLC Ultra-Performance Liquid Chromatography EPI-β-CD Epichlorohydrin-β-cyclodextrin BDE 1,4-Butanediol diglycidyl ether RI retention indices Declarations CRediT authorship contribution statement: Bassant MM Ibrahim: Project no “ 12060132” PI , Conceptualization, Methodology, Investigation, Data curation, Writing - original draft review & editing . Asmaa Badawy Darwish: Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Writing - original draft, review & editing. Sally Abou Taleb: Conceptualization, Methodology, Investigation, Data curation. Reda M. Mourad : Conceptualization, Noha Nazeeh Yassen : Methodology, Investigation, Formal analysis. Alyaa Farouk Hussein: Methodology, Investigation, Formal analysis. Shaimaa Ali Gad: Methodology, Investigation, Formal analysis Mona A. Mohammed: Project no “12060132” Co-PI, Conceptualization, Methodology, Investigation, Data curation, Writing - original draft, review & editing. Conflict of Interest: The authors don’t have any conflict of interest regarding the current manuscript. Funding: This study had been funded by the “National Research Centre” in Egypt, as a part of the project entitled : “Pharmacological investigation and Metabolomics study of promising anti-inflammatory herbal oils loaded in a polymeric nano-composite drug delivery system targeting Dermatitis and Upper Respiratory Allergy in rats”, under registration number. 12060132. Acknowledgment: As authors of this work, all of us would like to express our great thanks and appreciation to the “In house project unit of National Research Centre, Dokki, Egypt” for providing a lot of facilities for this work as a part of the project entitled “Pharmacological investigation and Metabolomics study of promising anti-inflammatory herbal oils loaded in a polymeric nano-composite drug delivery system targeting Dermatitis and Upper Respiratory Allergy in rats”, under registration number 12060132. Also, we would like also to express our deep gratitude and our grateful thanks to “Prof. Dr Hab. 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Supplementary Files GraphicalAbstract.jpg supl.docx Cite Share Download PDF Status: Published Journal Publication published 22 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 10 Apr, 2024 Reviewers agreed at journal 30 Mar, 2024 Reviews received at journal 25 Mar, 2024 Reviewers agreed at journal 05 Mar, 2024 Reviewers invited by journal 17 Feb, 2024 Editor assigned by journal 14 Feb, 2024 Editor invited by journal 04 Jan, 2024 Submission checks completed at journal 04 Jan, 2024 First submitted to journal 31 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3826210","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":265701463,"identity":"de78524d-9d9b-4fcd-bb5b-9c0fb92eebca","order_by":0,"name":"Bassant M.M. 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Mohammed","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBADfiBmgzCPNzAwE6NFsgGu5cwBkrXcSMCvRbe99+CHn3vsJPinHT724GfONjm+m28MPxdU2DDwt3cnYNNiduZcsmTPs2QJidtp6Ya9224bS97OMZaecSaNQeLM2Q1YtdzIMZDgOcBcx3A7x0yCd9vtxA23cwykedsOMxhI5OLSYvzzz4F6CXmgFsm/227Xb7h5xvg3AS1m0jwHDksYALVIA21JMLjBY4bfljNnzKxlDhyXMLydliYtu+224cwzaWXWPGfSeHD65XiP8c03B6ol5G4nH5N8u+22PN/xw5tv81TYyPG392LVgg1wGIBIHmKVgwD7A1JUj4JRMApGwfAHAG4RaS7w3I6WAAAAAElFTkSuQmCC","orcid":"","institution":"National Research Centre","correspondingAuthor":true,"prefix":"","firstName":"Mona","middleName":"A.","lastName":"Mohammed","suffix":""}],"badges":[],"createdAt":"2023-12-31 16:29:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3826210/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3826210/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-66297-2","type":"published","date":"2024-07-22T16:16:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":49319824,"identity":"27c07d3c-d59d-471b-9b91-d9c360596b89","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":774242,"visible":true,"origin":"","legend":"\u003cp\u003eIllustrates the numerical representation of the compounds listed in Table 3. The chemical structure depicted in Fig. 1 and Fig. S1 pertains to various groups, namely Group A-F, which encompasses cembrane-type diterpenoids, prenylaromadendrane-type diterpenoids, as well as tirucallane-type, ursane-type, oleanane-type, and lupane-type triterpenes. These compounds were identified in BC through the use of ethylacetate and total methanol extract.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/13ed0311adf35f19379ad38f.jpg"},{"id":49320167,"identity":"2a26ab9a-1340-4942-8b19-a216cc3bfbc9","added_by":"auto","created_at":"2024-01-08 16:11:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":526678,"visible":true,"origin":"","legend":"\u003cp\u003e(a) TEM micrographs of Nano sponges optimized formulations, (b) SEM micrographs of Nano sponges optimized formulations.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/1f95aac93453909a349884a4.jpg"},{"id":49319830,"identity":"7be8d980-ccb4-4804-a149-4fe4119c9c5b","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":298112,"visible":true,"origin":"","legend":"\u003cp\u003eIR spectrum of different Nano sponges components and optimized formulations.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/304aa70878791a91e2f19a2f.jpg"},{"id":49319826,"identity":"726ace94-d3d6-442a-9c4f-0fe778dc8372","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":126844,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIn-vitro \u003c/em\u003erelease profiles of drugs from Nano sponges optimized formulations (D1, D5, P1 and P5) at PBS 7.4.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/a6037cded5ef88435a51a6da.jpg"},{"id":49320166,"identity":"c6aea6ee-ebf5-4943-8692-058515229146","added_by":"auto","created_at":"2024-01-08 16:11:02","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":177966,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIn vitro\u003c/em\u003e study of DPPH\u003csup\u003e.\u003c/sup\u003e and ABTS\u003csup\u003e+\u003c/sup\u003e antioxidant activity for different extracts BC plant.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/a830c97b9609af66bbe5971c.jpg"},{"id":49319829,"identity":"30bae092-7bca-464f-b399-2dd750652867","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":799630,"visible":true,"origin":"","legend":"\u003cp\u003ePhotomicrographs of control groups: The lung of a negative control rat is more like a well-organized sponge consists of functional respiratory units alveoli (\u003cstrong\u003eA\u003c/strong\u003e); each alveolus shares its wall (inter-alveolar septum) with adjacent alveoli they are average thickness (\u003cstrong\u003eblack arrows\u003c/strong\u003e); \u003ca href=\"http://www.siumed.edu/~dking2/crr/rsguide.htm#bronchioles\"\u003ebronchioles\u003c/a\u003e \u0026nbsp;(\u003cstrong\u003eB\u003c/strong\u003e) lined by columnar epithelium supported by smooth muscle layer has normal appearance; bronchial vessels have normal looking and average thickness (\u003cstrong\u003ered arrow\u003c/strong\u003e).The trachea is lined by ciliated, \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified columnar epithelium\u003c/a\u003e (\u003cstrong\u003eblack star\u003c/strong\u003e); rests upon ordinary connective tissue Incomplete rings of \u003ca href=\"http://www.siumed.edu/~dking2/ssb/skeleton.htm#cartilage\"\u003ehyaline cartilage\u003c/a\u003e encircle the trachea (\u003cstrong\u003eTC\u003c/strong\u003e); muscle fibers of esophagus noticed (\u003cstrong\u003ered star\u003c/strong\u003e). The nasal cavity lined by \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified epithelium\u003c/a\u003e (\u003cstrong\u003ePSE\u003c/strong\u003e); mucosa and submucosa region filled of blood vessels (\u003cstrong\u003ered arrows\u003c/strong\u003e); mucin and serous secreting gland. The lung of a positive control rat; shows that alveoli with increased thickness wall (\u003cstrong\u003eblue arrow\u003c/strong\u003e); inflammatory cells infiltrates (\u003cstrong\u003eINF\u003c/strong\u003e); tracheal cartilage (\u003cstrong\u003eTC\u003c/strong\u003e); destructed pseudostratified columnar epithelium (\u003cstrong\u003eyellow star\u003c/strong\u003e); \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified epithelium\u003c/a\u003e(\u003cstrong\u003ePSE\u003c/strong\u003e); (H\u0026amp;E 100x,200x).\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/5022e45ede74fe71121b2fa0.jpg"},{"id":49319833,"identity":"c4f016e3-d9da-4237-a998-d228d3488bef","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1136544,"visible":true,"origin":"","legend":"\u003cp\u003ePhotomicrographs for tested groups (DEX salt, D1\u0026amp; D5) of lung, tracheal and nasal tissue: Alveoli with increased thickness wall\u003cstrong\u003e \u003c/strong\u003e(\u003cstrong\u003eblue arrow\u003c/strong\u003e);\u003cstrong\u003e \u003c/strong\u003ebronchioles(\u003cstrong\u003eB\u003c/strong\u003e); inflammatory cells infiltrates(\u003cstrong\u003eINF\u003c/strong\u003e); mucous(\u003cstrong\u003eM\u003c/strong\u003e); ciliated, pseudostratified columnar epithelium (\u003cstrong\u003eblack stars\u003c/strong\u003e); destructed pseudostratified columnar epithelium(\u003cstrong\u003eyellow stars\u003c/strong\u003e); tracheal cartilage(\u003cstrong\u003eTC\u003c/strong\u003e); \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified epithelium\u003c/a\u003e(\u003cstrong\u003ePSE\u003c/strong\u003e).\u003cstrong\u003e (\u003c/strong\u003eH\u0026amp;E 100x,200x\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/1f700c076ea028b91b8268e1.jpg"},{"id":49319831,"identity":"bef215e1-5205-4c86-9f3d-3102e0aa4844","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":1234888,"visible":true,"origin":"","legend":"\u003cp\u003ePhotomicrographs for tested groups (\u003cem\u003eBoswellia \u003c/em\u003eEtOAc extract, P1\u0026amp; P2) of lung, tracheal and nasal tissue: Alveoli with increased thickness wall (\u003cstrong\u003eblue arrow\u003c/strong\u003e); indentation of bronchial wall (\u003cstrong\u003ecurved arrow\u003c/strong\u003e); destructed bronchioles (\u003cstrong\u003eB\u003c/strong\u003e); inflammatory cells infiltrates (\u003cstrong\u003eINF\u003c/strong\u003e); destructed bronchial muscular walls (\u003cstrong\u003ered star\u003c/strong\u003e); destructed pseudostratified columnar epithelium (\u003cstrong\u003eyellow star\u003c/strong\u003e); tracheal cartilage (\u003cstrong\u003eTC\u003c/strong\u003e); \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified epithelium\u003c/a\u003e (\u003cstrong\u003ePSE\u003c/strong\u003e); edematous tissue (\u003cstrong\u003eE\u003c/strong\u003e) (H\u0026amp;E 100x,200x)\u003c/p\u003e","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/277609fa7a2709ec268b7226.jpg"},{"id":49319834,"identity":"9a21fe7d-24ee-471b-adb6-61719f78ecae","added_by":"auto","created_at":"2024-01-08 16:03:02","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":837572,"visible":true,"origin":"","legend":"\u003cp\u003ePhotomicrographs for tested groups of lung, tracheal and nasal tissue of groups treated with DF1 and DF2: Alveoli with increased thickness wall (\u003cstrong\u003eblue arrow\u003c/strong\u003e); alveoli with average thickness wall (\u003cstrong\u003eblack arrow\u003c/strong\u003e) ;indentation of bronchial wall (\u003cstrong\u003ecurved arrow\u003c/strong\u003e); bronchioles filled with mucus (\u003cstrong\u003eB\u003c/strong\u003e); inflammatory cells infiltrates (\u003cstrong\u003eINF\u003c/strong\u003e); ciliated, pseudostratified columnar epithelium (\u003cstrong\u003eblack star\u003c/strong\u003e); destructed pseudostratified columnar epithelium(\u003cstrong\u003eyellow star\u003c/strong\u003e); hemorrhagic foci (\u003cstrong\u003ered star\u003c/strong\u003e); tracheal cartilage(\u003cstrong\u003eTC\u003c/strong\u003e); \u003ca href=\"http://www.siumed.edu/~dking2/intro/epith.htm#pseudocol\"\u003epseudostratified epithelium\u003c/a\u003e (\u003cstrong\u003ePSE\u003c/strong\u003e). (H\u0026amp;E 100x,200x)\u003c/p\u003e","description":"","filename":"9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/1d7486c2e39f07cb79113756.jpg"},{"id":61597232,"identity":"55057875-d4ac-4f6d-a138-8edb8c43d0c4","added_by":"auto","created_at":"2024-08-01 17:32:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8979222,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/3aee1006-70fc-4e82-97f0-e19ed2ecb552.pdf"},{"id":49320165,"identity":"2d92a40e-1869-431c-ae95-3a8cff1c7951","added_by":"auto","created_at":"2024-01-08 16:11:02","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":86739,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/a151bd4bf0c949432577d16c.jpg"},{"id":49320168,"identity":"1f1a0f6e-b63d-45b1-b7a6-74da7fdc4464","added_by":"auto","created_at":"2024-01-08 16:11:02","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":50759,"visible":true,"origin":"","legend":"","description":"","filename":"supl.docx","url":"https://assets-eu.researchsquare.com/files/rs-3826210/v1/dc583969b8a6ea2d430972ae.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of enclosing terpenoids-rich Boswellia Carterri ethyl acetate extract in binary cyclodextrin based oligomer nano-complex for improving its activity via counteracting ICAM-1, Ilβ4 and LTB4 pathways in respiratory distressed rats","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cem\u003eBoswellia carterii\u003c/em\u003e, a member of the Burseraceae family, is widely distributed in Somalia and Ethiopia. Its bark contains secretory tissue that exudes a gum resin. This gum resin, known as olibanum, has been utilized as a medicinal substance in Unani (Islamic) and Chinese traditions for the treatment of various ailments including rheumatoid arthritis, osteoarthritis, dysmenorrhea, ulcers, swelling, and pain resulting from injuries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Previous studies examining the phytochemical and pharmacological properties of olibanum have demonstrated its diverse biological activities, such as anti-inflammatory effects [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], cytotoxic properties [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], neuroprotective properties [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], α-Glucosidase inhibition [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and antioxidant activity. Traditional Chinese medicine (TCM) has also employed olibanum to alleviate symptoms associated with traumatic injuries, chest congestion, pain [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and inflammatory diseases like rheumatoid arthritis. The resin of BC is widely recognized as a rich source of structurally diverse diterpenoids, with the major classes being triterpenes (such as boswellic acids), oleanane-type compounds, cembrane-type compounds, ursane-type compounds, tirucallane-type compounds, and oxygenated macrocyclic diterpenoid-type compounds. Additionally, prenylaromadendrane-type diterpenes have also been identified in this resin [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMaterials that are inhaled in the form of powder target the lungs, an inhaled pneumo-toxicant cause\u0026rsquo;s serious pulmonary damage via lipid peroxidation and even DNA breakdown [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Workers subjected to chronic talc powder inhalation are more susibtiple to silicosis and asbestosis, manifested by continuous cough and progressing dyspnoea. If the condition is left untreated, it will progress to pulmonary hypertension and fibrosis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Pulmonary talcosis occurs as a complication of inspiration of large amounts of talc powder [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Lung injuries as pneumonia, pleurisy, fibrosis, and haemorrhage were evidenced in rat\u0026rsquo;s lungs of rats that were subjected to talc powder inhalation. Addiction of talc-adulterated marijuana and prolonged inspiration of talc powder by quarry laborers, lead to talc pneumoconiosis, bronchiolar obstruction and bronchiolitis, and may be fatal [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne kind of corticosteroid medicines that has been widely used as an anti-asthmatic agent is DEX [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. DEX is an immunosuppressant with anti-inflammatory properties that can relieve the inflammation and pathophysiology of asthma [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Regrettably, the administration of oral corticosteroids over an extended period of time has been marred by the occurrence of systemic adverse reactions, such as renal insufficiency, hypotension, reduced body mass, conjunctival inflammation, and visual impairment, notwithstanding the drug's profound curative potency [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In view of this, there is a growing necessity to formulate a strategy to optimize the curative capabilities of corticosteroids while alleviating their systemic adverse effects [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe utilization of a pulmonary route for drug delivery is extremely attractive and has gained significant attention for the treatment of respiratory diseases and conditions. This is primarily due to the lung's expansive surface area, its rich blood supply, and its ability to effectively absorb medications for both local and systemic distribution [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In comparison to more conventional methods of drug delivery such as oral, peritoneal, and systemic administration, pulmonary medication delivery offers distinct advantages. By directly targeting the airway, this form of administration bypasses the first pass effect and allows for the precise treatment of pulmonary conditions. Consequently, medications delivered via the pulmonary route can elicit therapeutic effects at lower concentrations compared to alternative routes, thereby minimizing systemic side effects. However, it has been argued that a significant portion of inhaled corticosteroids remains within the oral cavity and permeates into the surrounding tissue, resulting in adverse effects [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In order to overcome these challenges in pulmonary medication delivery, the use of drug carriers that effectively transport pharmaceuticals to the desired site while maintaining appropriate drug concentrations within the airway is of utmost importance [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA considerable amount of effort has been devoted to the design of colloidal drug delivery systems in order to enhance the therapeutic effectiveness of drugs by modifying their bio-distribution and pharmacokinetics [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Liposomes, solid lipid nanoparticles, and polymeric nanoparticles have all undergone extensive investigation for drug delivery in the lungs. One of the innovative drug carriers that have recorded an enhanced effect is Nanosponges. Chemically crosslinked polymers known as Nanosponges are produced by reacting the CD unit with an appropriate crosslinking agent, such as CA, BDE, PMDA, CDI, or DPC [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. βCD-NS has an amazing ability to encapsulate. They create novel drug carriers, safeguard biodegradable materials, enhance the aqueous solubility of weakly water-soluble compounds, or provide long-lasting delivery systems. Parenteral, pulmonary, and oral routes can all be impacted by the spherical form and tiny size of NS [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe goal of this work is to prepare and evaluate ethylacetate extract from \u003cem\u003eBoswellia carterri\u003c/em\u003e and then Nano-sponge formulations loaded with DEX salt compared to \u003cem\u003eBoswellia carterri\u003c/em\u003e extract Nano-sponge for pulmonary administration intended for the treatment of respiratory allergies and asthma to enhance their efficacy, avoiding hepatic first-pass metabolism as well as the severe side effects that accompany orally administered drugs such as gastric irritation, and, moreover, to overcome compliance problems, thus providing better convenience of treatment.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003e2.1. Materials\u003c/h2\u003e\n\u003cp\u003eBC resins were gathered from the governorate of Khartoum in Sudan, where this collection was conducted in accordance with both local and national guidelines, as proper permission had been obtained for the collection of plant material. Dexamethasone Sodium Phosphate was graciously provided as a gift from the esteemed AMRIYA Pharmaceutical Industry Company in Egypt. Hydroxypropyl \u0026beta;-cyclodextrin (HP\u0026beta;-CD) (KLEPTOSE HPB, MW 1380) and epichlorohydrin-\u0026beta;-cyclodextrin (EPI-\u0026beta;-CD) were kindly supplied by the reputable company Roquette in France. Diphenyl carbonate (DPC) was procured from the esteemed establishment Acros Organics in Belgium. Prednisolone was obtained from the well-known Sigma Chemical Co. (St Louis, MO, U.S.A.). Disodium hydrogen phosphate anhydrous and Potassium dihydrogen phosphate were purchased from El-Gomhouria Pharmaceutical Chemicals in Egypt. The cellulose membrane was acquired from the esteemed company Sigma-Aldrich, chemie Gmbh, located in Steinheim, Germany. All other chemicals and solvents used are of chemical grade and were utilized without any additional purification.\u003c/p\u003e\n\u003cp\u003eTalc powder for induction of respiratory distress, was purchased from local medical suppliers; brand name \u0026ldquo;Five Fives Baby Mary Talcum\u0026rdquo;, it is high quality fragrance and clumps free powder, each powder pack weighs 200 gm. Diethyl ether and Formaldehyde were purchased from \u0026ldquo;Sigma Chemical Co., St. Louis, MO, USA\u0026rdquo;, the former for induction of anaesthesia before withdrawal of blood and the later for fixation of postmortem tissues. Diagnostic Elisa kits: \u0026ldquo;Intracellular adhesion molecule 1(ICAM-1-1), Leukotriene B4 (LTB 4), Interleukin\u0026beta; 4 (IL\u0026beta;4)\u0026rdquo;, for assessment of allergic and inflammatory markers levels in serum were purchased from \u0026ldquo;Elabscience Inc (USA)\u0026rdquo;, their measurement procedures followed the manufacturer\u0026rsquo;s guidelines. Trolox from Sigma Aldrich, all other chemicals and solvents were of high analytical grade.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimals\u003c/strong\u003e In the present study, female Wister albino rats were used. Fifty animals of body weights (150\u0026ndash;175 g) were obtained from the animal house colony of National research center in Egypt. They were housed in metal cages of uniform weights and designs, in well aeriated room at temperature range 22\u0026thinsp;\u0026plusmn;\u0026thinsp;3˚C, and humidity range 55\u0026thinsp;\u0026plusmn;\u0026thinsp;5%. Standard chow and free water access were available. The study was done in accordance with the guide for care and use of laboratory animals Approval of the ethics committee of \u0026ldquo;National Research Centre\u0026rdquo; numbered 19/209 was obtained prior to performance of the study[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]. The experiments were consistent with the civil regulations of \u0026ldquo;Animal Welfare and the Institutional Animal Ethical Committee (IAEC)\u0026rdquo;, and were congruent with the \u0026ldquo;Animal Research: Reporting of \u003cem\u003eIn vivo\u003c/em\u003e Experiments (ARRIVE)\u0026rdquo; guidelines[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003e2.2. Methods\u003c/h2\u003e\n\u003cdiv id=\"Sec5\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.1. Phytochemisty Section\u003c/h2\u003e\n\u003cdiv id=\"Sec6\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.1.1. Plant materials and Extraction\u003c/h2\u003e\n\u003cp\u003e\u003cem\u003eBoswellia carterii\u003c/em\u003e was acquired from the city of Khartoum, located in the Republic of Sudan. The desiccated resin, weighing 500 grams, underwent a comprehensive extraction process using 3 liters of methanol at ambient temperature, repeated thrice. Subsequently, the extract was subjected to filtration and concentrated under reduced pressure at a temperature of 45\u0026deg;C, employing a rotary evaporator[\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e]. The resulting unrefined residue was immersed in water, allowing for an overnight duration, and underwent a sequential partitioning procedure involving chloroform, followed by ethyl acetate, n-butanol, and ultimately, water[\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2.1.2. Phytochemicals screening of BC extracts\u003c/strong\u003e were conducted to identify the presence of various compounds. The methanolic, dichloromethane, ethylacetate, butanol and water extracts were examined for the presence of carbohydrates and/or glycosides using the a-naphthol sulphuric acid reagent, as previously described by Lewis and Smith[\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. Tannins were detected using the method developed by Shellard [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]. To test for alkaloids, one mL of the alcoholic extract filtrate was mixed with 2 mL of Dragendoff's reagent [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. The presence of alkaloids was indicated by the formation of a turbid orange color. Mayer's reagent was used as a confirmation test for alkaloids, and the appearance of a yellow precipitate confirmed their presence [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]. The potential presence of flavonoids was determined by the formation of a yellow color according to Trease and Evans [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]. Additionally, the extracts were treated with magnesium / HCl, and the formation of a red color indicated the possible presence of flavanones and/or flavonol [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Saponins were identified if a froth persisted for approximately 30 minutes[\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]. Lastly, a green coloration in the upper layer and a deep red color in the lower layer indicated the presence of steroids and triterpenoids, respectively, as reported by Hanson [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.1.3. Metabolomics of secondary metabolites from BC resins using LC/MS/MS.\u003c/h2\u003e\n\u003cp\u003e10 mg of two extract were dissolved in 1 ml of 80% concentration methanol and then filtrated by a sarangi filter. The diluted extract was repeated three times.\u003c/p\u003e\n\u003cp\u003eThe UPLC system (specifically the Acquity system from Waters, located in Milford, USA) was connected to the Q-Exactive hybrid MS/MS quadrupole - Orbitrap mass spectrometer (manufactured by Thermo in Germany). To achieve chromatographic separation in this system, a water solution acidified with 0.1% formic acid (referred to as solvent A) and acetonitrile (referred to as solvent B) were used, with a mobile phase flow rate of 0.3 mL/min. The gradient for the separation process was as follows: from 0 to 7 minutes, the composition changed from 50% solvent A to 50% solvent B, and from 7 to 15 minutes, it transitioned to 98% solvent B. These conditions were maintained for a total of 17 minutes. The separation was performed using the BEH shield C18 column, which had dimensions of 150\u0026times;2.1 mm and 1.7 \u0026micro;m particle sizes. The Q-Exactive MS was operated with the following settings by Piasecka et al., [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.1.4. Processing Data\u003c/h2\u003e\n\u003cp\u003eWe have developed a methodology for determining the fragmentation patterns of 49 metabolites using mass spectrometry. This comprehensive approach includes information on retention time and MS/MS data. The raw MS data for the two fractions (methanol and ethylacetate) of BC metabolites were exported in a standardized output format (abf) and analyzed using MS-DIAL 4.18, a software tool that offers improved and standardized untargeted metabolomics data analysis. To eliminate noisy spectra, the MSP format was employed along with a classical spectral similarity calculation. The potential metabolites of interest were identified by comparing their fragmentation patterns and RI with those found in the Reaxys, KNAPSACK, and RIKEN databases. [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.2. Nano-section\u003c/h2\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.2. 1. Preparation of Nano sponges\u003c/h2\u003e\n\u003cp\u003eA modified version of the ultrasound-assisted synthesis approach was employed to synthesize NSs. Diphenyl carbonate, employed as a cross-linker, and HP\u0026beta;-CD, utilized as a polymer, was combined in distilled water at a predetermined molar ratio [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e shows the ratios of HP\u0026beta;-CD: DPC that were employed (1:5, 3:1, 4:1, and 5:1). At 90\u0026deg;C, the mixture was sonicated, and then homogenized in a hot water bath for seven minutes at 12,000 rpm. After being moved to falcon tubes, the mixture was centrifuged for 30 minutes at 6000 rpm. Following centrifugation, the medication was added, and the mixture was shaken at 150 rpm for the whole night. The mixture was centrifuged at 6000 for 30 minutes at room temperature after being sonicated at 90\u003csup\u003eo\u003c/sup\u003eC the next day. After transferring the mixture to a petri dish and adjusting the volume for freeze drying, it was kept at 25\u0026ordm;C until needed again. This process will yield spherical, uniformly sized nano sponges.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.2. Determination of Encapsulation efficiency (EE%)\u003c/h2\u003e\n\u003cp\u003eThe samples underwent filtration by means of a 0.22 \u0026micro;m membrane filter and were subsequently subjected to analysis at the predetermined \u0026lambda;\u003csub\u003emax\u003c/sub\u003e, specifically at 242 nm [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e], utilizing an ultraviolet-visible (UV) spectrophotometer (Pharma spec 1700, Shimadzu, Japan). The estimation of encapsulation efficiency for all ratios was conducted through the utilization of the subsequent equation: EE% = \u003cem\u003e(M\u003c/em\u003e\u003csub\u003e\u003cem\u003eact\u003c/em\u003e\u003c/sub\u003e \u003cem\u003e/ M\u003c/em\u003e\u003csub\u003e\u003cem\u003ethe\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e)\u003c/em\u003e X 100\u003c/p\u003e\n\u003cp\u003eWhere M\u003csub\u003eact\u003c/sub\u003e = actual DEX content in weighed quantity of Nano sponges, and M\u003csub\u003ethe\u003c/sub\u003e = theoretical DEX content in Nanosponges [\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.3. Vesicle size, polydispersity index and Zeta Potential Measurement\u003c/h2\u003e\n\u003cp\u003eThe samples distributed in double-distilled water were subjected to examination of PS, ZP, and PDI using Zeta-sizer (Nano Series ZS90, Malvern Instruments Ltd., Worcestershire, UK) and dynamic light scattering (DLS)[\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.4. Preparation of the Optimized formulations:\u003c/h2\u003e\n\u003cp\u003eFollowing the completion of earlier trials, the ideal molar ratio for generating DEX salt NSs with the best EE%, PS, and ZP values was chosen to be the optimum formulation. Then, BC plant extract NSs (P1) were prepared using the chosen molar ratio of HP\u0026beta;-CD: DPC. In the meantime, a novel complex containing HPB-CD and epichlorohydrin-\u0026beta;-cyclodextrin (EPI-\u0026beta;-CD) was created at the chosen molar ratio, and it was loaded with plant extract (P2) and Dex salt (D5) as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. The new formulations were prepared using the same procedure that was described in section 2.2.5.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.5. Determination of EE%, PS, ZP and PDI of the optimized formulations:\u003c/h2\u003e\n\u003cp\u003eAs stated in section (2.2.6), the resulting DEX salt and plant formulation's EE% was measured at predetermined \u0026lambda;\u003csub\u003emax\u003c/sub\u003e 242 and 252 nm respectively. Table\u0026nbsp;(4) displays the composition, encapsulation efficiency, and physico-chemical parameters of the optimized formulations.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.6. Characterization of the optimized formulations\u003c/h2\u003e\n\u003cdiv id=\"Sec16\" class=\"Section5\"\u003e\n\u003ch2\u003e2.2.2.6.1. Surface Morphology\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003eTransmission Electron Microscopy (TEM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe selected formulations' morphological features were analyzed through the use of TEM (JEOL Co., JEM-2100, Japan). After applying one drop of the diluted sample to a carbon-coated copper grid, the samples were stained after the grid had dried for fifteen minutes at room temperature. The grid was sprayed with a drop of 1%w/v phosphotungstic acid solution, allowed to stand for three minutes, and then placed under the microscope to examine the samples at the appropriate magnifications for surface characteristics and shape.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eScanning Electron Microscopy (SEM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing a scanning electron microscope (SEM) (Quanta FEG 250, ThermoFisher Scientific Co., Czech Republic), the surfaces of the chosen formulations were analyzed. Using double-sided tape, freeze-dried samples were attached to aluminum stubs and then coated with a thin layer of gold using a sputter coater unit. The SEM was run at a distance of 10 mm and an acceleration voltage of 20 kV.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section5\"\u003e\n\u003ch2\u003e2.2.2.6.2. Fourier transform infrared spectroscopy (FTIR)analysis.\u003c/h2\u003e\n\u003cp\u003eFT-IR analysis was used to identify any potential interactions between the blend of chosen formulations and the Nano sponge\u0026rsquo;s components. The infrared spectrum (400\u0026ndash;4000 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) was used to scan the samples (JASCO 6100, Tokyo, Japan). Potassium bromide pellets were used to prepare the FT-IR samples.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.2.7. In-vitro release Study\u003c/h2\u003e\n\u003cp\u003eIn this investigation, release study of DEX and Plant NSs formulations (D1, D5, P1 and P2) as well as free DEX and Plant solutions was performed. The dialysis bags, specifically made of Dialysis tubing cellulose membrane obtained from Sigma-Aldrich Co., located in St. Louis, USA, with a molecular weight cut-off ranging from 12,000 to 14,000, were appropriately filled with a quantity equivalent to 2 mg of the NSs formulations alongside aqueous solutions of DEX and plant extract. Prior to being suspended in screw-capped glass containers with a capacity of 100 ml, which were also filled with 100 ml of PBS with a pH value of 7.4 in order to maintain sink condition, the dialysis bags were meticulously sealed on both ends to effectively prevent any leakage from occurring. It is worth noting that this procedure was done to ensure the integrity and accuracy of the results [\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e43\u003c/span\u003e]. The entire experiment took place within a controlled environment, namely a thermostatic shaking water bath provided by Memmert, model SV 1422, which is a reputable brand based in Germany. The temperature was set at a constant 37\u0026deg;C with a tolerance of 0.5\u0026deg;C, while the shaking speed was maintained at 100 revolutions per minute. Throughout the course of the experiment, samples were regularly collected at specific time intervals and simultaneously replaced with an equal volume of the designated replacement release medium. This meticulous process was carried out to sustain the desired sink state and ensure the reliability of the findings. In order to compare the DEX and plant concentrations in the removed samples to blanks that had received the same treatment, spectrophotometric analysis was used. By dividing the amount of drug released by the amount of drug in the dialysis bag at the beginning, the cumulative release percentages were calculated. Three distinct samples were used for each measurement, which was done in triplicate.\u003c/p\u003e\n\u003cp\u003eNumerous mathematical models, including Higuchi's square root of time model and zero and first order kinetic models, were used in the kinetic investigation of drug release from NSs formulations[\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e]. The plots of Q vs. t in the case of zero order, log (Q\u003csub\u003e0\u003c/sub\u003e - Q) vs. t for first order, and Q vs. t\u003csup\u003e1/2\u003c/sup\u003e for the Higuchi model were used to derive the R\u003csup\u003e2\u003c/sup\u003e values that indicate the coefficient of determination. Where (Q) is the amount of drug that has been released at time (t) and (Q\u003csub\u003e0\u003c/sub\u003e - Q) is the amount of drug that is still present at time (t). The most accurate model was considered to have the highest correlation coefficient values or determination coefficient (R\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\" class=\"Section3\"\u003e\n\u003ch2\u003e2.2.3. \u003cstrong\u003ePharmacological section\u003c/strong\u003e\u003c/h2\u003e\n\u003cdiv id=\"Sec20\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.3.1. In vitro study of DPPH and ABTS antioxidant activity\u003c/h2\u003e\n\u003cp\u003eThe method employed to evaluate the in vitro antioxidant activity of two BC plant extracts was the DPPH and ABTS free radical-scavenging activity method. Different concentrations (70, 50, 30, 20, 10, 5, 2.5, 1.5, 1 and 0.5\u0026micro;g/mL) were utilized for this purpose. As a positive control, ascorbic acid and trolox were employed[\u003cspan class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThe estimation of ABTS\u0026thinsp;+\u0026thinsp;in various extracts was conducted using the methodologies outlined by Dinkova-Kostova et al. [\u003cspan class=\"CitationRef\"\u003e46\u003c/span\u003e]. The DPPH (1,1-diphenyl-2-picrylhydrazyl, 250 mM) radical scavenging assay was carried out as described by Mohammed et al[\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e]. To calculate the percentage inhibition of the DPPH and ABTS\u0026thinsp;+\u0026thinsp;radicals, the following formula was utilized: % inhibition = [(A\u003csub\u003econtrol\u003c/sub\u003e - A\u003csub\u003esample\u003c/sub\u003e)/A\u003csub\u003econtrol\u003c/sub\u003e] x 100. In the case of DPPH, A represents the absorbance at 517 nm, while for ABTS+, A is the absorbance at 734 nm [\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.3.2. In vivo Pharmacological study\u003c/h2\u003e\n\u003cdiv id=\"Sec22\" class=\"Section5\"\u003e\n\u003ch2\u003e2.2.3.2.1. Experimental design of the efficacy study\u003c/h2\u003e\n\u003cp\u003eFifty female Wistar albino rats were used for evaluation of the efficacies of the \u003cem\u003eBoswellia carterii\u003c/em\u003e extract, DEX salt and the tested formulations. The rats were divided into 10 equal groups (n\u0026thinsp;=\u0026thinsp;5). Rats in group I acted as the negative control group and received oral saline solution 0.9%. The other nine groups were exposed to 50 mg/m\u003csup\u003e3\u003c/sup\u003e talc for 6 hours daily, 5 days/week for 4 weeks for induction of respiratory distress [\u003cspan class=\"CitationRef\"\u003e49\u003c/span\u003e]. After 4 weeks of exposure to talc powder, they were subdivided into the following groups: group II which was untreated and served as positive control group, and treated groups III, IV, V, VI, VII, VIII, IX and X which received Dexa salt, D1, D5, \u003cem\u003eBoswellia carterii\u003c/em\u003e plant extract, P1, P2, Drug-free NSs DF1,, Drug-free NSs DF2, respectively. All were given in doses of 10 \u0026micro;l which was equivalent to 20 \u0026micro;g of each substance. All were instilled in each nostril (IN) for 4 weeks following cessation of exposure to talc powder.\u003c/p\u003e\n\u003cp\u003eEach rat was examined daily pre and post exposure to talc powder and during treatment to observe any symptoms of respiratory distress such as either apnoea or dyspnoea manifested by cyanosis around mouth, panting or lethargy. After the terminal treatment dose, the rats were fasted for about 16 hours before blood sampling for biochemical assay and dissection for histopathological examination [\u003cspan class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec23\" class=\"Section5\"\u003e\n\u003ch2\u003e2.2.3.2.2. Blood sampling and biochemical estimation of Anti-inflammatory and anti-allergic biomarkers:\u003c/h2\u003e\n\u003cp\u003eSixteen hours after last dose of treatment, all rats were anaesthetized and the \u0026ldquo;retro-orbital plexus of veins\u0026rdquo; was punctured for blood sampling. Then the samples were placed in the centrifuge and the rotating speed was set at 1500 rpm for duration of 10 min in order to get clear serum.\u003c/p\u003e\n\u003cp\u003eBiochemical analysis was done by using \u0026ldquo;ELISA kits\u0026rdquo; following manufacturer\u0026rsquo;s guidelines for rat \u0026ldquo;ICAM-1-1, IL\u0026beta;4 or leukotriene B4\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eELISA Tests Principles\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ELISA kit employed the principle of \"Sandwich-ELISA\". The kits were equipped with micro ELISA plates that had already been coated with an antibody that specifically targeted either Rat ICAM-1, IL\u0026beta;-4, or leukotriene B4. The micro ELISA plate wells were then subjected to the addition of standards or samples, which were subsequently combined with the specific antibody. Following this, a biotinylated detection antibody that specifically targeted either Rat ICAM-1-1, IL\u0026beta;4, or leukotriene B4, as well as Avidin-Horseradish Peroxidase (HRP) conjugate, were added successively to each micro plate well and incubated. The removal of free components was achieved through a thorough washing process. Subsequently, the addition of the substrate solution to each well took place. It was observed that only the wells containing rat ICAM-1-1, IL\u0026beta;4, or LTB4 displayed a blue coloration resulting from the presence of the biotinylated detection antibody and Avidin-HRP conjugate. The enzyme-substrate reaction was brought to a halt by the addition of the stop solution, leading to a yellow coloration.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eThe spectrophotometer was employed to measure the optical density (OD) at a wavelength of 450 nm\u0026thinsp;\u0026plusmn;\u0026thinsp;2 nm. It was established that the OD value was directly proportional to the concentration of either Rat ICAM-1-1, IL\u0026beta;4, or LT B4.\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eThe concentrations of rat serum ICAM-1-1, IL\u0026beta;4, or LTB4 were determined by comparing the OD of the samples to the standard curve.\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\" class=\"Section5\"\u003e\n\u003ch2\u003e2.2.3.2.3. Tissue preparation for histopathological examination:\u003c/h2\u003e\n\u003cp\u003eAll animals were sacrificed by euthanasia. All parts of the upper and lower respiratory tract from each animal were excised and fixed in 10% neutral formalin solution for 24 hours, followed by washing with tap water, dehydrating in alcohol, clearing in xylene and ultimately embedding in paraffin[\u003cspan class=\"CitationRef\"\u003e51\u003c/span\u003e]. Serial sections of 3 \u0026micro;m thickness were cut followed by staining with hematoxylin and eosin [\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e], for preparation for histopathological examination. All images were captured at \u0026ldquo;The Pathology Lab in the National research Centre in Egypt\u0026rdquo; by using the image analysis system with a light microscope \u0026ldquo;Olympus CX41\u0026rdquo; and \u0026ldquo;SC100 video camera\u0026rdquo; that were attached to a computer system. All the photomicrographs that were taken at different magnifications were processed using \u0026ldquo;Adobe Photoshop version 8.0\u0026rdquo;.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec25\" class=\"Section4\"\u003e\n\u003ch2\u003e2.2.3.4. Statistical analysis\u003c/h2\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n\u003cp\u003eAll values were expressed as means of the results of biochemical parameters plus or minus the standard error. Comparisons between all means were conducted using the One Way Analysis of Variance (ANOVA) followed by the Tukey Kramer's test for multiple comparisons. A significance level of P\u0026thinsp;\u0026le;\u0026thinsp;0.001 was considered statistically significant. The eighth version of the Graph pad prism software was utilized to perform all the statistical tests [\u003cspan class=\"CitationRef\"\u003e52\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"3. Results and discussions","content":"\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1. Phytochemical screening of Boswellia Carterii and their fractions\u003c/h2\u003e\n \u003cp\u003eAfter defatted resin powder, 100% methanol (2L) was added and kept overnight on shaking 120 rpm. The solvent was evaporated by rotary evaporator at 40\u003csup\u003eo\u003c/sup\u003eC till dryness. The crude residue was suspended in water, left for a duration of 24 hours, and subsequently divided into four portions using 0.8ml of chloroform, followed by 0.8ml of ethyl acetate, 0.8ml of n-butanol, and finally 0.8ml of water.\u003c/p\u003e\n \u003cp\u003eThe findings demonstrated the existence of flavonoids, carbohydrates, tannins, triterpenoids, steroids, alkaloids, and saponin. These substances were displayed in (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Flavonoids and saponin were detected in the ethyl acetate, butanol, and water extracts. These findings align with the outcomes reported by [\u003cspan class=\"CitationRef\"\u003e53\u003c/span\u003e], who identified the presence of flavonoids, carbohydrates, saponins, tannins, phenol, coumarins, and triterpenes. However, carbohydrates and tannins were not present in the chloroform extract (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003ePhytochemical screening of \u003cem\u003eBoswellia carterii\u003c/em\u003e and their fractions.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGroups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBoswellia carterii resins\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCH\u003csub\u003e2\u003c/sub\u003eCL\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEtOAc\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en-Butanol\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVolatile Oils\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e++\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eˉ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eˉ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eˉ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCarbohydrate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTannins\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFlavonoids, NaOH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFlavonoids (Shinoda test)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSaponin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSterol and / or triterpenes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoumarins\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e++\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlkaloids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003e(++), (+) and (-) refer to high, low and absente amount respectively\u003c/strong\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. \u003cstrong\u003eUPLC-HRMS profiles of\u003c/strong\u003e \u003cstrong\u003eBC-\u003c/strong\u003e \u003cstrong\u003eresins by LC-MSMS\u003c/strong\u003e.\u003c/h2\u003e\n \u003cp\u003eThe metabolomics profiles of compounds examined by LC-MS/MS of \u003cem\u003eBoswellia carterii\u003c/em\u003e (BC) were documented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. This table includes a total of 49 compounds and is visually illustrated in (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Cembrane-type diterpenes, which are a diverse group of oxygenated macrocyclic diterpenoids composed of 14-membered rings, represent a prominent class of secondary metabolites predominantly found in the coral genera \u003cem\u003eSinularia\u003c/em\u003e, \u003cem\u003eSarcophyton\u003c/em\u003e, \u003cem\u003eLobophytum\u003c/em\u003e, \u003cem\u003eTabacoo\u003c/em\u003e, and \u003cem\u003eBoswellia\u003c/em\u003e. Twenty-six diterpenoids, classified as sixteen cembrane-type diterpenoids boscartins and ten prenylaromadendrane-type diterpenoids boscartols, along with twenty known triterpenoids, belong to nine tirucallane-types, six ursane-type, three oleanane-type, and two lupane-type. Their structure elucidations were achieved by the LC-MSMS examination. Compounds listed in the table were found in total methanol and ethylacetate extract; these are compounds compared with the literature, compounds identified from the electronic databases as KNApSAcK databases, and compounds identified from MS_Dial. This paper deals with many of the literature searches listed in (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003emetabolomics profiles of listed compounds by LC-MSMS.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eRT\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eCompounds Names/ SMILES\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eChemical formula\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eMass\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e∆ ppm\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ePDA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eExtracts\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003emeasured \u0026amp;calculated\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eexact mass of [M\u0026thinsp;+\u0026thinsp;H]\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003emeasured \u0026amp;calculated\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eexact mass of [M-H]-\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEtOAc\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth colspan=\"12\" align=\"left\"\u003e\n \u003cp\u003eGroup A: Cembrane-type diterpenoids\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartins T\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eO\u0026thinsp;=\u0026thinsp;C(/C([H])\u0026thinsp;=\u0026thinsp;C1\\[H])CC[C@@]([H])(O)[C@](CC2)(C)O[C@]2([H])[C@@]3(C)CC[C@@]1(O3)C(C)C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323.2212,\u003c/p\u003e\n \u003cp\u003e323.2217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305.1740[C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e287.2006[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e241.1590[C\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e21\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e321.2116,\u003c/p\u003e\n \u003cp\u003e321.2060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e199.1695[C\u003csub\u003e12\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.6244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartin E\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eO[C@H](/C\u0026thinsp;=\u0026thinsp;C1\\C)C[C@](O2)(C)[C@@H]2C[C@]3(C(C)C)CC[C@](O3)(C)[C@H](O)CC1\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e353.2231,\u003c/p\u003e\n \u003cp\u003e353.2244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e334.2079[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e316.198[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e181.0866[C\u003csub\u003e10\u003c/sub\u003eH1\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e352.2176,\u003c/p\u003e\n \u003cp\u003e352.2166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e333.2071[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e307.1914[C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-3.8969/\u003c/p\u003e\n \u003cp\u003e2.8182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartin J\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eC/C(CC/C\u0026thinsp;=\u0026thinsp;C1/C)\u0026thinsp;=\u0026thinsp;C\\C[C@]2(C(C)C)CC[C@](O2)(C)[C@H](O)C[C@@H]1O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH34O\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323.2563,\u003c/p\u003e\n \u003cp\u003e323.2581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305.2480[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e287.2345[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e321.2107,\u003c/p\u003e\n \u003cp\u003e321.2060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303.2893[C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e39\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e199.1694[C\u003csub\u003e12\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-5.4270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e238\u003c/p\u003e\n \u003cp\u003e277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncensole oxide\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCC(C)[C@@]12CC[C@](C)([C@@H](O)CC/C(C)\u0026thinsp;=\u0026thinsp;C/CC[C@](O3)(C)C3([H])C2)O1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323.2582,\u003c/p\u003e\n \u003cp\u003e323.2561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305.2461[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e287.2353[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO],\u003c/p\u003e\n \u003cp\u003e263.1628[C\u003csub\u003e16\u003c/sub\u003eH\u003csub\u003e23\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003cp\u003e151.1118[C\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartin C\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCC(C)[C@@]12CC[C@](C)(C(O)CC/C(C)\u0026thinsp;=\u0026thinsp;C/C(O)C[C@]3(C)C(O3)([H])C2)O1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e339.2531,\u003c/p\u003e\n \u003cp\u003e339.2530\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303.2318[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e285.2211[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO],\u003c/p\u003e\n \u003cp\u003e151.1119[C\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e337.2383,\u003c/p\u003e\n \u003cp\u003e337.2373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e293.2118[C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1937/\u003c/p\u003e\n \u003cp\u003e2.8029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartins P\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e[H][C@@]12C[C@@]3(CC[C@@](C)(O3)[C@]3([H])CC[C@@](C)(O)[C@]([H])(CC[C@@]1(C)O2)O3)C(C)C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e339.2526,\u003c/p\u003e\n \u003cp\u003e339.2529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e321.2422[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e303.2321[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e285.2202[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO],\u003c/p\u003e\n \u003cp\u003e251.1997[C\u003csub\u003e16\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003cp\u003e151.1119[C\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e337.2383,\u003c/p\u003e\n \u003cp\u003e337.2373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e319.1923[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.2456/\u003c/p\u003e\n \u003cp\u003e2.8029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartins X\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCC(C)[C@@]12CC[C@@](C)(O1)[C@H](CC\\C(C)\u0026thinsp;=\u0026thinsp;C\\CCC(=\u0026thinsp;C)[C@H](O)C2)OC(C)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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align=\"left\"\u003e\n \u003cp\u003e-2.2633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245,\u003c/p\u003e\n \u003cp\u003e274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e56\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartin B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCC(C)[C@@]12CC[C@](C)([C@]3([H])CC[C@](O3)(C)C(O)CC4(O[C@@]4(C)C(O)C2)[H])O1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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align=\"left\"\u003e\n \u003cp\u003e13.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIncensole\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCC(C)[C@@]12CC[C@](C)([C@@H](O)CC/C(C)\u0026thinsp;=\u0026thinsp;C/CC/C(C)\u0026thinsp;=\u0026thinsp;C/C2)O1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e307.2643,\u003c/p\u003e\n \u003cp\u003e307.2632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e289.2521[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8612\u003c/p\u003e\n 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class=\"CitationRef\"\u003e58\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup B: Prenylaromadendrane-type diterpenoids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartol M\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12C(CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)[C@@]13[H])[C@]2(C)C(O)\\C\u0026thinsp;=\u0026thinsp;C\\C(C)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305.2107,\u003c/p\u003e\n \u003cp\u003e305.2111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e287.2002[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e269.1889[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303.1996,\u003c/p\u003e\n \u003cp\u003e303.1955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e285.0402[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.3020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartol K\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)C3[C@]1([H])C2(C)[C@H](O)C1OC(=\u0026thinsp;O)C(C)\u0026thinsp;=\u0026thinsp;C1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e333.2046,\u003c/p\u003e\n \u003cp\u003e333.2060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e315.1955[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e297.1836[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e331.1914,\u003c/p\u003e\n \u003cp\u003e331.1904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e313.1810[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4.3398/\u003c/p\u003e\n \u003cp\u003e3.0811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartol P\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)CC\\C\u0026thinsp;=\u0026thinsp;C(\\C)COC(C)\u0026thinsp;=\u0026thinsp;O\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e347.2581,\u003c/p\u003e\n \u003cp\u003e347.2581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e311.2367[C\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO],\u003c/p\u003e\n \u003cp\u003e243.2315[C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e59\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscarterol A\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)C3C1[C@@]2(C)\\C\u0026thinsp;=\u0026thinsp;C\\C\u0026thinsp;=\u0026thinsp;C(\\C)CO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303.2318,\u003c/p\u003e\n \u003cp\u003e303.2319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e285.2214[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO],\u003c/p\u003e\n \u003cp\u003e245.1908[C\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscarterol F\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)\\C\u0026thinsp;=\u0026thinsp;C\\C\u0026thinsp;=\u0026thinsp;C(\\C)C\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e300.2085,\u003c/p\u003e\n \u003cp\u003e300.2084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e282.1932[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e26\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.3331\u003c/p\u003e\n \u003c/td\u003e\n 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\u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e303.2312,\u003c/p\u003e\n \u003cp\u003e303.2319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e285.2215[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e29\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.2626\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartol C\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)[C@@]3([H])[C@]1([H])[C@@]2(C)CC\u0026thinsp;=\u0026thinsp;CC(C)(C)O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305.2476, 305.2475\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e287.2359[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e31\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1697\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBoscartol G\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CCC(=\u0026thinsp;C)[C@]3([H])CC[C@](C)(O)C3[C@]1([H])[C@@]2(C)[C@@]1([H])[C@H](O)C\u0026thinsp;=\u0026thinsp;C(C)C1\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e28\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e317.2112,\u003c/p\u003e\n \u003cp\u003e317.2111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e299.2011[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e281.1895[C\u003csub\u003e20\u003c/sub\u003eH\u003csub\u003e25\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e315.1965,\u003c/p\u003e\n \u003cp\u003e315.1955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e297.2439[C\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e271.2071[C\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e27\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3827/\u003c/p\u003e\n \u003cp\u003e3.3693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup C: Polyphenolics and derivatives\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuinic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e191.0552,\u003c/p\u003e\n \u003cp\u003e191.0550\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e173.0440[C\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e85.0279[C\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-Dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGallic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171.0289,\u003c/p\u003e\n \u003cp\u003e171.0288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e153.0184[C\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e127.0393[C\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169.0131, 169.0131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125.0229[C\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e], 59.0122[C\u003csub\u003e2\u003c/sub\u003eH\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.1609/\u003c/p\u003e\n \u003cp\u003e0.3190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e202,241, 267\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-Dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFisetin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e285.0403,\u003c/p\u003e\n \u003cp\u003e285.0394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171.1019[C\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e151.0024[C\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e127.1116[C\u003csub\u003e8\u003c/sub\u003eH\u003csub\u003e15\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-Dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup D: Triterpenes belong to tirucallane-type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSacraoic acid C\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@](CCC\u0026thinsp;=\u0026thinsp;C(C)C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]1([H])CC[C@]2(C)C3\u0026thinsp;=\u0026thinsp;C([C@@H](O)C[C@@]12C)[C@@]1(C)CC[C@@H](O)C(C)(C)[C@]1([H])CC3\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e487.3425,\u003c/p\u003e\n \u003cp\u003e487.3418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e451.3221[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e316.3476[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e44\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e485.3280,\u003c/p\u003e\n \u003cp\u003e485.3262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e441.3381[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e45\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003cp\u003e383.2964[C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e39\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8159\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245,\u003c/p\u003e\n \u003cp\u003e306\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e62\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSacraoic acid D\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@](CCC\u0026thinsp;=\u0026thinsp;C(C)C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]1([H])CC[C@]2(C)C3\u0026thinsp;=\u0026thinsp;C(C(=\u0026thinsp;O)C[C@@]12C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@]1([H])CC3\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e44\u003c/sub\u003e O\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e485.3256,\u003c/p\u003e\n \u003cp\u003e485.3262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e467.3158[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e449.3051[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e41\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e483.3117,\u003c/p\u003e\n \u003cp\u003e483.3105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e439.3220[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e381.2796[C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e37\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1260/\u003c/p\u003e\n \u003cp\u003e-1.0887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245,\u003c/p\u003e\n \u003cp\u003e310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e62\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpirosacraoic acid B\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@](CCC\u0026thinsp;=\u0026thinsp;C(C)C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]1([H])CC[C@]2(C)C(=\u0026thinsp;O)[C@@]3(CC[C@@]12C)[C@H](O)C[C@]1([H])[C@]3(C)CCC(=\u0026thinsp;O)C1(C)C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e487.4325,\u003c/p\u003e\n \u003cp\u003e487.3418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e469.3294[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e45\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e423.3261[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e485.3275,\u003c/p\u003e\n \u003cp\u003e485.3262\u003c/p\u003e\n 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align=\"left\"\u003e\n \u003cp\u003e451.3221[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e422.3123[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e42\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e466.3163,\u003c/p\u003e\n \u003cp\u003e466.3156\u003c/p\u003e\n \u003cp\u003e[M-2H]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e423.3271[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e371.2592[C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e35\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0031/\u003c/p\u003e\n \u003cp\u003e1.6240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOlibanumol G\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eO[C@@H]1C(C)(C)[C@]2(O)CC[C@@]3(C)[C@]4(C)CC[C@](CC[C@H]5C(C)\u0026thinsp;=\u0026thinsp;C)(C)[C@]5([H])C4CC[C@]3([H])[C@@]2(C)CC1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e50\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e442.3782,\u003c/p\u003e\n \u003cp\u003e442.3805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e424.3640[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-5.2624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e61\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta;-Boswellic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12[C@@H](C)[C@H](C)CC[C@]1(C)CC[C@]1(C)C2\u0026thinsp;=\u0026thinsp;CC[C@]2([H])[C@@]3(C)CC[C@@H](O)[C@](C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]3([H])CC[C@@]12C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n 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\u003cp\u003e1.5808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e11-Keto-\u0026beta;-boswellic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12[C@@H](C)[C@H](C)CC[C@]1(C)CC[C@]1(C)C2\u0026thinsp;=\u0026thinsp;CC(=\u0026thinsp;O)[C@]2([H])[C@@]3(C)CC[C@@H](O)[C@](C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]3([H])CC[C@@]12C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e471.3470,\u003c/p\u003e\n \u003cp\u003e471.3469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e407.3328[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e469.3320,\u003c/p\u003e\n \u003cp\u003e469.3312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e407.3329[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3384/\u003c/p\u003e\n \u003cp\u003e1.5636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrsolic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12[C@@H](C)[C@H](C)CC[C@@]1(CC[C@]1(C)C2\u0026thinsp;=\u0026thinsp;CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e455.3532,\u003c/p\u003e\n \u003cp\u003e455.3520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e311.1710\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e66\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsiatic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eO\u0026thinsp;=\u0026thinsp;C([C@]12CC[C@@H](C)[C@H](C)[C@@]1([H])C3\u0026thinsp;=\u0026thinsp;CCC4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@]5([H])CC[C@@]4(C)[C@]3(C)CC2)O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e487.3430,\u003c/p\u003e\n \u003cp\u003e487.3418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e469.3322[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e45\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e373.2738[C\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e37\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup F: Triterpene belong to oleanane Type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOleanolic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]1(C)C2\u0026thinsp;=\u0026thinsp;CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e457.3687,\u003c/p\u003e\n \u003cp\u003e457.3678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e411.3257[C28H43O2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-dial\u003c/p\u003e\n \u003cp\u003eKNApSAcK\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eBeta-Elemonic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eC/C(C)\u0026thinsp;=\u0026thinsp;C\\CCC(C(O)\u0026thinsp;=\u0026thinsp;O)C1CCC2(C)C1(C)CCC3\u0026thinsp;=\u0026thinsp;C2CCC4C3(C)CCC(C4(C)C)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e455.3542,\u003c/p\u003e\n \u003cp\u003e455.3520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e437.3424[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e45\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e419.33324[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e453.3004,\u003c/p\u003e\n \u003cp\u003e453.2999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e435.2917[\u003csub\u003eC29\u003c/sub\u003eH\u003csub\u003e39\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e409.3105[C\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e41\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.7978/\u003c/p\u003e\n \u003cp\u003e0.9890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eElemonic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@](CCC\u0026thinsp;=\u0026thinsp;C(C)C)(C(O)\u0026thinsp;=\u0026thinsp;O)[C@]1([H])CC[C@]2(C)C3\u0026thinsp;=\u0026thinsp;C(CC[C@@]12C)[C@@]1(C)CCC(=\u0026thinsp;O)C(C)(C)[C@]1([H])CC3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e454.3445,\u003c/p\u003e\n \u003cp\u003e454.3441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e436.3305[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e44\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e408.3334[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e44\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e452.3375,\u003c/p\u003e\n \u003cp\u003e452.3363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e435.3270[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.8731/\u003c/p\u003e\n \u003cp\u003e2.6529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e65\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaslinic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@@]12CC(C)(C)CC[C@@]1(CC[C@]1(C)C2\u0026thinsp;=\u0026thinsp;CC[C@]2([H])[C@@]3(C)C[C@@H](O)[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)\u0026thinsp;=\u0026thinsp;O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e471.3477,\u003c/p\u003e\n \u003cp\u003e471.3469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e427.3571[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e47\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e385.3084[C\u003csub\u003e26\u003c/sub\u003eH\u003csub\u003e41\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.7628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup G: Triterpene belong to lupane type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u0026beta;,20-dihydroxylupane-28-oic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@]12[C@@H](CC[C@@]1(CC[C@]1(C)[C@]2([H])CC[C@]2([H])[C@@]3(C)CC[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)\u0026thinsp;=\u0026thinsp;O)C(C)(C)O\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e50\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e475.3786,\u003c/p\u003e\n \u003cp\u003e475.3782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e457.3683[C\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e49\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e],\u003c/p\u003e\n \u003cp\u003e411.3262[C\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e]\u003c/p\u003e\n \u003cp\u003e335.2579[C\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e35\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e473.3604,\u003c/p\u003e\n \u003cp\u003e473.3625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.2927/\u003c/p\u003e\n \u003cp\u003e-4.4223\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e67\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlphitolic acid\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e[H][C@]12[C@@H](CC[C@@]1(CC[C@]1(C)[C@]2([H])CC[C@]2([H])[C@@]3(C)C[C@@H](O)[C@H](O)C(C)(C)[C@]3([H])CC[C@@]12C)C(O)\u0026thinsp;=\u0026thinsp;O)C(C)\u0026thinsp;=\u0026thinsp;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e471.3480,\u003c/p\u003e\n \u003cp\u003e471.3469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e407.3301[C\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e43\u003c/sub\u003eO]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup H: Fatty acids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOleic acid, methyl ester\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e36\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e295.2640,\u003c/p\u003e\n \u003cp\u003e295.2632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e245.2508[C\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e33\u003c/sub\u003eO\u003csub\u003e8\u003c/sub\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8812\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMs-dial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe preliminary identification was made using the entire extract of BC and the ethyl acetate fraction. The letters signify the compounds that were compared with existing literature, the compounds that were identified using the KNApSAcK database, the compounds that were identified using MS_Dial, and the compounds that were identified using Metlin.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cp\u003eTable 3\u003c/p\u003e\n \u003cp\u003eAnti-inflammatory effects of tentative identified compounds of BC-Resins.\u003c/p\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClass of groups\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRoles as Chronic Anti-inflammatory; Promoting effect / Inhibiting effect\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRefs\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCembrane-type diterpenoids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe production of TNF-\u0026alpha; and IL-6 as well as the expression of iNOS, COX-2, and p-NF-\u0026kappa;B are significantly hindered by this compound. Moreover, this compound has demonstrated a greater inhibitory potential against the inflammatory agent 5-lipoxygenase.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e68\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrenylaromadendrane-type diterpenoids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThis group has shown powerful inhibitory effects on the production of NO.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTriterpenes belong to tirucallane, ursane\u003c/strong\u003e, \u003cstrong\u003eoleanane\u003c/strong\u003e and \u003cstrong\u003elupane type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFurthermore, these types possess the ability to prevent the production of leukotriene in neutrophilic granulocytes through the inhibition of 5-lipoxygenase. Furthermore, a few boswellic acids have the capacity to impede the growth of cancer cell lines, induce apoptosis, block topoisomerases, and inhibit elastase in leukocytes.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e67\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePolyphenolics and derivatives\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThey exhibit inhibitory effects on phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), resulting in a decrease in the synthesis of prostaglandins (PGs) and leukotrienes (LTs), thereby exhibiting anti-inflammatory properties.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e70\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3. Preparation of Nanosponges\u003c/h2\u003e\n \u003cp\u003eNano sponges based on cyclodextrin have become more well-known recently because of their special qualities. These sponges especially improve the stability and apparent solubility of medications by creating inclusion complexes through the inner nanocavities of cyclodextrins and non-inclusion complexes through the gaps in the cross-linked polymeric network of the sponges. Cyclodextrin-based nanostructures (NSs) such as HP\u0026beta;-CD can provide a promising class of cross-linked polymers with an amazing three-dimensional architecture consisting of hydrophilic and hydrophobic nanosized pores that can effectively encapsulate a wide range of drugs and improve the solubility of less soluble drugs[\u003cspan class=\"CitationRef\"\u003e71\u003c/span\u003e]. In the present study, NSs were prepared by ultrasound assisted technique. This method produces NSs with spherical shape and uniform in size [\u003cspan class=\"CitationRef\"\u003e72\u003c/span\u003e]. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the formulation components as well as the findings reached from the evaluation of the responses. DEX NSs was created in the current study utilizing HP\u0026beta;-CD as the polymer and DPC as the crosslinker in varied ratios (1:5, 3:1, 4:1, and 5:1). NSs were effectively prepared in all of the formulations examined.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eComposition, entrapment efficiency and physico-chemical properties of DEX NSs and the optimized NSs Formulation.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eCode\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eDrug\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eMolar Ratio\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eEE% \u0026plusmn; SD\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eVS\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePDI\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eZP\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003e2-Hydroxy propyl-\u0026beta;-cyclodextrin\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(2HP-\u0026beta;-CD)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePolymerized-\u0026beta;-cyclodextrin\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(Epi-\u0026beta;-CD)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eDi-phenyl carbonate\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(DPC)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eD1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e166.8\u0026thinsp;\u0026plusmn;\u0026thinsp;26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-27\u0026thinsp;\u0026plusmn;\u0026thinsp;6.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eD2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e109.1\u0026thinsp;\u0026plusmn;\u0026thinsp;32.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-22.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eD3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e105.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-20.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eD4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.8\u0026thinsp;\u0026plusmn;\u0026thinsp;24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-26.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eD5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDEX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100%\u0026plusmn;6.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e74.04\u0026thinsp;\u0026plusmn;\u0026thinsp;55.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-29.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eP1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEtoAc Extract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.39%\u0026plusmn;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e244\u0026thinsp;\u0026plusmn;\u0026thinsp;17.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-25.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eP2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEtoAc Extract\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e98.56%\u0026plusmn;2.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e359\u0026thinsp;\u0026plusmn;\u0026thinsp;30.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.458\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-28\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\n \u003ch2\u003e\u003cem\u003e3.4.\u003c/em\u003e Encapsulation efficiency\u003c/h2\u003e\n \u003cp\u003eThe EE% values for each DEX NSs formulation (D1\u0026ndash;D4) are displayed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. All formulations had EE% values between 98.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 and 99.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40%. The success of DEX NS preparation was confirmed by the obvious high encapsulation efficiency (EE%) of all prepared NSs. The excellent crosslinking between HP\u0026beta;-CD and DPC, which permits a large inclusion of DEX salt in the NSs matrix and cyclodextrin cavity, may be responsible for the high EE% of the generated NSs [\u003cspan class=\"CitationRef\"\u003e73\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e74\u003c/span\u003e]. Along with the inclusion of DEX salt in the porous matrix of the Nano sponge, it is also responsible for entirely trapping the drug molecules as an inclusion complex inside the hydrophobic host cyclodextrins\u0026apos; cavities, which are surrounded by hydrophilic nanochannels [\u003cspan class=\"CitationRef\"\u003e75\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e76\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5. Vesicle size, polydispersity index and Zeta Potential\u003c/h2\u003e\n \u003cp\u003eThe analysis of DEX NSs revealed that all produced NSs were in the nanosized range, with formulation sizes ranging from 105.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9 to 166.8\u0026thinsp;\u0026plusmn;\u0026thinsp;26.3 nm (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). It has been observed that formulations comprising a higher molar ratio of crosslinker exhibited PS greater than those comprising a lower molar ratio of crosslinker. This finding is in good agreement with previous reports [\u003cspan class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e78\u003c/span\u003e], where the increase in crosslinker molar ratio resulted in a larger PS. Additionally, the data supported low polydispersity index (PDI) values of 0.371 to 0.612, which indicated a uniform and constrained vesicle size distribution [\u003cspan class=\"CitationRef\"\u003e79\u003c/span\u003e]. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e also shows that all of the formulations under investigation had a negatively charged zeta potential; this could be because of the free hydroxyl groups of \u0026beta;CD and 2-HP\u0026beta;CD, as well as the carbonyl groups of DPC [\u003cspan class=\"CitationRef\"\u003e80\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e81\u003c/span\u003e]. All formulations under investigation had absolute ZP values more than 20, which are more than enough to maintain the individual particles\u0026apos; separation from one another by electrostatic repulsion. Thus, scattered particles are therefore physically stable.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec32\" class=\"Section2\"\u003e\n \u003ch2\u003e3.6. Selection of the optimized DEX salt and ethylacetate plant extract NSs formulations:\u003c/h2\u003e\n \u003cp\u003eAccording to the results of EE%, PS, PDI and ZP, the best molar ratio between HP\u0026beta;-CD and DPC was (1:5) (D1). The same molar ratio HP\u0026beta;-CD: DPC (1:5), was used for the preparation of Plant extract NSs (P1) and the same molar ratio was used for the preparation of NSs using HP\u0026beta;-CD and EPI-\u0026beta;-CD in the ratio of (1:5) and loading of DEX and ethylacetate extraction in the new formulations (D5 and P2). The \u0026lambda;\u003csub\u003emax\u003c/sub\u003e of the plant extract was found to be at 252nm. The EE%, PS, PDI and ZP of the new formulations were estimated and demonstrated in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Results revealed that new formulations D5, P1 and P2 exhibited high EE% (87.39%\u0026plusmn;1.99 to 100\u0026thinsp;\u0026plusmn;\u0026thinsp;6.24), with particle size in the nano size range, low PDI and suitable ZP value. It was noticed that there was non-significant difference (p\u0026thinsp;\u0026ge;\u0026thinsp;0.001) in EE% between D1 and D5 as use of EPI-\u0026beta;-CD instead of DPC doesn\u0026rsquo;t affect EE% of DEX salt, On the other hand the use of EPI-\u0026beta;-CD in the preparation of ethylacetate plant extract NSs lead to a significant increase (p\u0026thinsp;\u0026le;\u0026thinsp;0.001) in EE%. Since few years, studies have been carried out toward the use of epichlorohydrin-\u0026beta;-cyclodextrin (EPI-\u0026beta;-CD) polymer for the preparation of Nano sponges [\u003cspan class=\"CitationRef\"\u003e82\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e83\u003c/span\u003e], as this polymerized form of \u0026beta;-cyclodextrin remains within the cavity structure of \u0026beta;-CD providing capability of forming inclusion complexes with a variety of guest molecules which can lead to increase the loading capacity of NSs [\u003cspan class=\"CitationRef\"\u003e84\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec33\" class=\"Section2\"\u003e\n \u003ch2\u003e3.7. Characterization of the optimized Formulations\u003c/h2\u003e\n \u003cdiv id=\"Sec34\" class=\"Section3\"\u003e\n \u003ch2\u003e3.7.1. Surface Morphology\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003eTransmission Electron Microscopy (TEM)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (a) depicts the morphology of NSs. The NSs have been found to be round and uniform, with no drug crystals on the surface. According to the figures, the NSs created using the ultrasonic assisted process have a uniform size distribution, crystallinity, and a porous character [\u003cspan class=\"CitationRef\"\u003e85\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eScanning Electron Microscopy (SEM)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe SEM images of NSs were illustrated in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e (b). SEM analysis of the prepared NSs revealed nano-sized spherical particles having multiple pores on their surface [\u003cspan class=\"CitationRef\"\u003e86\u003c/span\u003e]. There was no residual crystals from the drugs indicating the complete encapsulation of drugs in the polymer [\u003cspan class=\"CitationRef\"\u003e87\u003c/span\u003e].\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec35\" class=\"Section3\"\u003e\n \u003ch2\u003e3.7.2. Fourier transform infrared spectroscopy analysis\u003c/h2\u003e\n \u003cp\u003eThe interactions between pharmaceuticals and excipients were investigated by comparing the FTIR spectra of pure components with drug-loaded Nano sponges (D1, D5, P1 and P2) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). The FTIR spectra of HP-\u0026beta;-CD showed prominent absorption bands at 3415 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (O-H stretching), 2929 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (C-H stretching), 1645 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (H-O-H bending), 1157 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (C-O stretching), and 1031 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (C-O-C stretching) [\u003cspan class=\"CitationRef\"\u003e88\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e89\u003c/span\u003e]. FTIR spectrum bands for DPC revealed distinctive absorbance band at 1753 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for carbonate bond [\u003cspan class=\"CitationRef\"\u003e90\u003c/span\u003e]. Epichlorohydrin-\u0026beta;-cyclodextrin (EPI-\u0026beta;-CD) has distinctive peaks for epichlorohydrin at 1288.36, 1249.79, and 721.33 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, respectively, as well as a CH\u003csub\u003e2\u003c/sub\u003eCl wagging band and C-Cl stretching in its IR spectra. The OH, CH\u003csub\u003e2\u003c/sub\u003e, and C-O-C stretching vibrations, which are approximately 3452.34, 3411.84, 3271.05, 2933.53, and 1099.35 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, respectively, confirm that cyclodextrin is present in the structure [\u003cspan class=\"CitationRef\"\u003e91\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eThe FTIR spectra of DPC showed distinctive peaks at 1513, 1509, 1480, 1397, 1314, 1312, 1214, 1210, 1176 and 1120 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e that can be assigned to C\u0026thinsp;=\u0026thinsp;H bending vibrations. The molecule containing carbonyl group shows strong absorption band for C\u0026thinsp;=\u0026thinsp;O stretching vibrations at the region 1850 and 1550 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e [\u003cspan class=\"CitationRef\"\u003e92\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eDEX exhibited distinct absorbance bands at 1706, 1660, and 1616 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, which were attributed to -C\u0026thinsp;=\u0026thinsp;O stretching vibrations connected to C3-cyclic and C20 carbonyl groups, as well as double bond context coupled to -C\u0026thinsp;=\u0026thinsp;O bonds. Furthermore, two more different absorption bands of 3468 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 1270 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e were realized due to the stretching ambiences of the O-H and C-F bonds, respectively [\u003cspan class=\"CitationRef\"\u003e93\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e94\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eThe comparative nature of the IR spectrum of BC ethylacetate plant extract can be observed when compared to Boswellia acids. It is worth noting that the spectrum exhibits characteristic peaks at specific wavenumbers, namely 3437 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (indicative of OH stretching), 2932 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (associated with C-H stretching), 1697 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (highlighting C\u0026thinsp;=\u0026thinsp;O stretching of aryl acid), 1453 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (pertaining to C-H bending), 1375 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (linked to COO symmetric stretching of carboxylates), 1240 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (relating to C-CO-C stretching of aryl ketone), as well as 1025 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 988 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (both associated with ring structures of cyclohexane) [\u003cspan class=\"CitationRef\"\u003e95\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eIn the distinctive peaks of DEX or ethylacetate plant extract, the IR spectrum of the optimized Nano sponge formulations (D1, D5, P1 and P2) revealed a shifting and diminished intensity. This shift in the characteristic peaks may be explained by the presence of physical interactions between drugs and various NS elements, such as Van der Wall bonds, hydrogen bonds, or dipole interactions, without any chemical changes to the drugs\u0026apos; structure after encapsulation, which can result in the best possible entrapment of DEX or ethylacetate plant extract in Nano sponges [\u003cspan class=\"CitationRef\"\u003e80\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e96\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e97\u003c/span\u003e].\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec36\" class=\"Section2\"\u003e\n \u003ch2\u003e3.8. In- vitro Release Study:\u003c/h2\u003e\n \u003cp\u003eCD-based NSs can be a useful technique for delivering medications in a sustained manner. Drug encapsulation in a crosslinked NSs structure allows for prolonged drug administration, allowing for lower doses, less side effects, and changed pharmacokinetics. These characteristics can be used to improve medicine distribution [\u003cspan class=\"CitationRef\"\u003e98\u003c/span\u003e]\u003c/p\u003e\n \u003cp\u003eThe prepared NSs formulations (D1, D5, P1 and P5) release profiles were shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. The tested formulations\u0026apos; release profiles displayed a biphasic behavior, with an initial quick release lasting for the first six hours. This first rapid release may have been caused by the drug\u0026apos;s adsorption on the NSs surface vesicles, which led to a fast release from NSs [\u003cspan class=\"CitationRef\"\u003e99\u003c/span\u003e]. Followed by a delayed, slow release for 24 hours.\u003c/p\u003e\n \u003cp\u003eFrequent administration is the main disadvantage of the majority of the traditional, commercially available drug delivery devices. The medication, however, is kept and released gradually over time after being loaded into the Nano sponge. It has been previously reported that hydrophilic cyclodextrin Nano sponges are used to adjust the drug release rate, as it facilitates medication absorption over biological barriers and it may help to protect the medication throughout its passage through the stomach [\u003cspan class=\"CitationRef\"\u003e100\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e101\u003c/span\u003e].\u003c/p\u003e\n \u003cp\u003eThe correlation coefficient (R\u003csup\u003e2\u003c/sup\u003e) values of NSs formulations demonstrated a superior fit to Higuchi\u0026apos;s model compared to the zero order and first order kinetic models. This conclusion was drawn from a linear regression analysis of the mathematical models employed to analyze the release data obtained from the NSs formulations. The R\u003csup\u003e2\u003c/sup\u003e values ranged from 0.8752 to 0.9943. In instances where a high degree of linearity was observed, the Peppas equation was utilized to further investigate the release process of DEX and plant material [\u003cspan class=\"CitationRef\"\u003e102\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e103\u003c/span\u003e]. According to the Peppas theory, if the value of n\u0026thinsp;=\u0026thinsp;0.43, the drug release process adheres to Fickian diffusion. When 0.43\u0026thinsp;\u0026lt;\u0026thinsp;n\u0026thinsp;\u0026lt;\u0026thinsp;0.85, the release process deviates from Fickian diffusion and follows anomalous (non-Fickian) diffusion. A value of n\u0026thinsp;=\u0026thinsp;0.85 signifies case II transport, while n\u0026thinsp;\u0026gt;\u0026thinsp;0.85 indicates super-case II transport [\u003cspan class=\"CitationRef\"\u003e102\u003c/span\u003e]. The range of values for the release exponent \u0026quot;n\u0026quot; in the NSs formulations varied from 0.213 to 0.452, thereby suggesting a release mechanism controlled by Fickian diffusion.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec37\" class=\"Section2\"\u003e\n \u003ch2\u003e3.9. Pharmacological Study\u003c/h2\u003e\n \u003cdiv id=\"Sec38\" class=\"Section3\"\u003e\n \u003ch2\u003e3.9\u003cem\u003e.1. In vitro\u003c/em\u003e antioxidants activity of \u003cem\u003eBoswellia Carterri\u003c/em\u003e extracts\u003c/h2\u003e\n \u003cp\u003eThe effects of the time of interaction of several antioxidants on the suppression of the absorbance of the ABTS\u0026thinsp;+\u0026thinsp;radical cation at 734 nm for the standard reference compounds, trolox and ascorbic acid, are shown in Table (S1). The total extract, dichloromethane fraction, ethyl acetate fraction, butanol fraction, and water fraction values are compared with those of the two standards.\u003c/p\u003e\n \u003cp\u003eNumerous studies have been conducted on the antioxidant properties of vitamin C, trolox, and natural resin extract compounds. Therefore, the purpose of this study is to determine the antioxidant activity of standard compounds generated from different resins with respect to their ability to scavenge DPPH and ABTS radicals. Hazardous free radicals in humans are stabilized in large part by the DPPH and ABTS radical scavenging tests.\u003c/p\u003e\n \u003cp\u003eTable (S1) presents the effects of the duration of interaction of specific antioxidants on the suppression of the absorbance of the ABTS\u003csup\u003e\u003cstrong\u003e+\u003c/strong\u003e\u003c/sup\u003e radical cation at 734 nm for trolox, ascorbic acid, the standard reference compounds. The values of the two standards are compared with those of total extract, dichloromethane fraction, ethyl acetate fraction, butanol fraction, and water fraction.\u003c/p\u003e\n \u003cp\u003eThe antioxidant activity of natural resin extract substances and Vit C and Trolox has been extensively studied. As a result, this study aims to identify the antioxidant activity of standard substances derived from various resins in terms of their DPPH radical scavenging activity and ABTS radical scavenging activity. The DPPH and ABTS radical scavenging assays play a crucial role in stabilizing harmful free radicals in the human body by providing a redox-functioned proton ion for unstable free radicals. This is accomplished by utilizing the fact that unstable violet DPPH and ABTS free radicals convert into stable yellow DPPH free radicals through the acceptance of a hydrogen ion from antioxidants. In this particular study, the results of the antioxidant activities assessed through the DPPH assay reveal that the BC resin ethyl acetate extract exhibits the highest antioxidant activity in both methods (IC\u003csub\u003e50\u003c/sub\u003e 0.5325 and 0.5527, respectively). It is followed by the butanol fraction as an agent (IC\u003csub\u003e50\u003c/sub\u003e 0.932 and 0.6476, respectively) when compared to the other extract samples and standard VitC and Trolox (Tables S1 and S2 and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe two methodologies employed in this section to gauge the antioxidant activity mutually corroborated one another, as all fractions were taken into account. This implies that the examined extracts may possess comparable chemical groups, and their effects can be attributed to these groups [\u003cspan class=\"CitationRef\"\u003e104\u003c/span\u003e]. In this regard, the identification and characterization of Cembrane-type diterpenoids, Prenylaromadendrane-type diterpenoids, Triterpenes belonging to tirucallane, ursane, oleanane, and lupane types, as well as polyphenolics, prove instrumental in the development of natural antioxidant substances derived from BC resins.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec39\" class=\"Section3\"\u003e\n \u003ch2\u003e3.9.2. In vivo Pharmacological study\u003c/h2\u003e\n \u003cp\u003eIn the present study, observation of the negative control rats didn\u0026rsquo;t reveal any abnormal respiratory sign as their nostrils appearances and nasal colours were normal as well as their attitudes towards the examiner and caregiver, these signs were confirmed with the measured biochemical parameters of allergy and inflammation as \u0026ldquo;ICAM-1, Il\u0026beta;4 and LTB\u003csub\u003e4\u003c/sub\u003e\u0026rdquo;, that were estimated in their sera, and were significantly less than the positive control group (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Histopathological examination of the lungs of the same group showed that they were more like a well-organized sponge consisting of functional respiratory units alveoli, each alveolus shared its wall (inter-alveolar septum) with adjacent alveoli, they were average thickness, the bronchioles were lined by columnar epithelium supported by smooth muscle layer had normal appearance and the bronchial vessels had normal looking and average thickness. The tracheas were lined by ciliate pseudostratified columnar epithelium, resting upon ordinary connective tissue with incomplete rings of hyaline cartilage. The nasal cavities were lined by pseudostratified epithelial mucosa and submucosal regions were filled of blood vessels, mucin and serous secreting gland (Fig.\u0026nbsp;6)\u003c/p\u003e\n \u003cp\u003eOn the other hand, signs of severe induced respiratory distress in all the rats that were powdered with talc powder for 4 weeks, and then left untreated for another 4 weeks (positive control group), were manifested by decreased food consumption, avoidance, irritability, increased aggression towards the researcher and the care-giver, hair ruffling, increased nasal discharge, nasal oedema and discolouration, together with significant elevation of ICAM-1, Il\u0026beta;4 and LT B4, compared to the negative control group (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). Talc powder causes dryness of the tracheobronchial mucosa and impairs its ciliary function, moreover, the adsorption of the surfactant to the magnesium silicate powder augments the lung injury, in addition to the pathological signs that include oedema, inflammation of the bronchial, epithelium,, diffuse infiltrates, and lung injury, that lead to acute respiratory distress syndrome [\u003cspan class=\"CitationRef\"\u003e105\u003c/span\u003e]. This explains the histopathological findings that were obtained on examination of tissues excised from rats of the positive control group in our study, which revealed that lung tissues were massively infiltrated with inflammatory cells infiltrates with germinal formation and destruction of bronchial walls, also the alveolar walls were thickened due to infiltration by inflammatory cells. Examination of the tracheal tissue revealed severe destruction of the tracheal lining with inflammatory cells infiltrate of submucosal tissue, and destruction of tracheal cartilage. Moreover, nasal tissue examination revealed that the nasal cavity was lined by pseudostratified epithelium, mucosa and submucosa region filled of blood vessels, mucin and serous secreting gland (Fig.\u0026nbsp;6).\u003c/p\u003e\n \u003cp\u003eTreatment with conventional DEX salt preparation didn\u0026rsquo;t improve either the biochemical parameters as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e or the histopathological picture in Fig.\u0026nbsp;7, when compared to the positive control group. On the contrary, it significantly elevated the ICAM-1 compared to positive control group. The same was for the group treated with D1; however, it has significantly lowered the Il\u0026beta;4 levels only, when compared to positive control group, without affecting the levels of ICAM-1 or LTB\u003csub\u003e4\u003c/sub\u003e, denoting that it exerted only an anti-inflammatory effect without any anti-allergic potential. The best effect of DEX salt treatment was obtained with D5, as it significantly lowered the ICAM-1 and Il\u0026beta;4, however it significantly elevated the LTB\u003csub\u003e4\u003c/sub\u003e levels in sera, which means that it has both anti-inflammatory and to some extent anti-allergic therapeutic potentials on respiratory tract allergies. The biochemical investigations were confirmed by histopathological examination of lung tissues excised from DEX salt treated group, as it was found that the lung tissues were mostly destructed by severe infiltration of inflammatory cells with focal areas of mucin; while, lungs of D1 and D5 treated groups showed infiltration of inflammatory cells with evidence of germinal formation and thickened alveolar walls. Tracheal tissue of DEX salt treated group, showed that the tracheal lining was destructed and rested upon connective tissue infiltrated by inflammatory cells and focal areas of mucin; on the other hand, tracheas of D1 and D5 treated groups have been improved. Nasal tissue revealed for all groups that the nasal cavity was lined by pseudostratified epithelium, mucosa and the submucosa region filled of blood vessels, mucin and serous secreting gland (Fig.\u0026nbsp;7).\u003c/p\u003e\n \u003cp\u003eTreatment with \u003cem\u003eBoswellia\u003c/em\u003e extract and its Nano sponge\u0026rsquo;s formulations (P1 and P2) improved significantly, but with different extents, all the biochemical parameters mentioned in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, when compared to both conventional DEX salt and positive control groups. Histopathological examination of lung tissues of Boswellia extract treated group revealed that the lung was more likely to be destructed by massive inflammatory cells infiltrates which also destructed the muscular walls of the bronchi, and totally invaded their lumens. Also the group treated with P1 formulation showed destructive bronchial architecture by inflammatory cells, and some had focal formation, the alveolar walls were infiltrated by inflammatory cells, the same picture was presented in the group treated with P2 formulation, which showed indentation of bronchial lining with evidence of intra-bronchial mucous with destruction of bronchial and alveolar walls due to inflammatory cells infiltration. Examination of tracheal tissues of Boswellia extract group and the group treated with P2 formulation revealed hyperplastic columnar epithelium with inflammatory cells infiltrates. Also the group treated with P1 formulation showed massively destructed tracheal lining as it was infiltrated by inflammatory cells. Nasal tissue examination revealed for Boswellia extract group and the group treated with P2 formulation showed disturbed mucosal region by edema and inflammatory cell infiltrate, this picture is improved in the group treated with P1 formulation as there are minimal inflammatory cell infiltrate with congested dilated blood vessels within mucosa and submucosal region (Fig.\u0026nbsp;8).\u003c/p\u003e\n \u003cp\u003eRegarding treatment with Drug-free NSs (DF1 and DF2), they showed significant less levels of ICAM-1, when compared to conventional DEX salt group, but didn\u0026rsquo;t significantly show any difference in levels when compared to the positive control group; yet, it was significantly higher than Boswellia extract group level. The levels of Il\u0026beta;4 and LTB\u003csub\u003e4\u003c/sub\u003e in both groups were significantly less than positive control and conventional DEX salt groups, but higher than Boswellia extract group (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). This indicates that drug-free nano-sponge have relative anti-allergic and anti-inflammatory effects but not limited to respiratory tract allergy only. Histopathological examination of lung tissues of the group treated with DF1 showed massively inflammatory cells infiltrates with destruction of bronchial walls; while, the group treated with DF2 showed more infiltration of inflammatory cells, with germinal formation also the alveolar walls were thickened due to infiltration by inflammatory cells. On the other hand, examination of tracheal tissue of the group treated with DF1, revealed more destruction of the tracheal lining with inflammatory cells infiltrate of submucosal tissue. The previous pathological picture showed improvement with minimal inflammatory cells infiltrate in the group treated with DF2. Nasal tissue examination of both groups showed that the nasal cavity was lined by pseudostratified epithelium, mucosa and submucosa region filled of blood vessels, mucin and serous secreting gland (Fig.\u0026nbsp;9).\u003c/p\u003e\n \u003cp\u003e\u0026ldquo;Intercellular adhesion molecule 1 (ICAM-1)\u0026rdquo;, is a bispecific antibody that is extensively expressed on the respiratory epithelial cells of allergic patients [\u003cspan class=\"CitationRef\"\u003e106\u003c/span\u003e]. ICAM-1 protein increases in airways of asthmatics [\u003cspan class=\"CitationRef\"\u003e107\u003c/span\u003e]. Therefore, its level is a strong indicator of the effect of allergen and therapeutics, which target the respiratory system. Based on this fact, the results of the present study suggest that, the best effect obtained was that of Boswellia extract in Nano-sponge (P1), as it significantly lowered the ICAM-1 when compared to the positive control group and was near the normal level when compared to negative control group without significant difference, moreover it was significantly less than both conventional DEX salt and Boswellia extract levels.\u003c/p\u003e\n \u003cp\u003eLeukotrienes LTB\u003csub\u003e4\u003c/sub\u003e is a lipid mediator that participates in the incidence of severe asthma or asthmatic exacerbations via acting as a potent neutrophil chemoattractant and via activation of CD\u003csub\u003e4\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;T cells, eosinophils and macrophages. That\u0026rsquo;s why, its blockage is the target for respiratory allergies and asthma control [\u003cspan class=\"CitationRef\"\u003e108\u003c/span\u003e]. Additionally, the cytokine \u0026ldquo;Interleukin 4 (IL\u0026beta;-4)\u0026rdquo; plays a crucial role in induction and differentiation of T- helper cells. One of the major causes of asthma and inflammatory airway diseases are induced via IL\u0026beta;-4 [\u003cspan class=\"CitationRef\"\u003e109\u003c/span\u003e]. It was found in the present study that BC extract in Nano-sponge P1 also, lowered significantly both Il\u0026beta;4 and LTB\u003csub\u003e4\u003c/sub\u003e levels compared to both conventional DEX salt and positive control group.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEffects of treatment with Boswellia Carterii ethylacetate plant extract, Dexa salt and their Nano Sponge formulations on inflammatory and allergic mediators of respiratory tract\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eICAM-1 (pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIl\u0026beta;4 (pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLTB\u003csub\u003e4\u003c/sub\u003e(pg/ml)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eNegative control\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e351\u0026thinsp;\u0026plusmn;\u0026thinsp;13.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1490\u0026thinsp;\u0026plusmn;\u0026thinsp;8.477\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2660\u0026thinsp;\u0026plusmn;\u0026thinsp;29.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive control\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(untreated talcosis)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1323\u0026thinsp;\u0026plusmn;\u0026thinsp;12.94\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4604\u0026thinsp;\u0026plusmn;\u0026thinsp;36.11 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3973\u0026thinsp;\u0026plusmn;\u0026thinsp;19.57 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDexa salt\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2652\u0026thinsp;\u0026plusmn;\u0026thinsp;101.4 \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4666\u0026thinsp;\u0026plusmn;\u0026thinsp;88.82 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4401\u0026thinsp;\u0026plusmn;\u0026thinsp;85.77 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDEX NSs (D1) (20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1501\u0026thinsp;\u0026plusmn;\u0026thinsp;8.197 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3715\u0026thinsp;\u0026plusmn;\u0026thinsp;33.05 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3973\u0026thinsp;\u0026plusmn;\u0026thinsp;60.05 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDEX NSs (D5) (20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e400\u0026thinsp;\u0026plusmn;\u0026thinsp;7.579\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3524\u0026thinsp;\u0026plusmn;\u0026thinsp;16.12 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5168\u0026thinsp;\u0026plusmn;\u0026thinsp;229 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Carterii\u003c/strong\u003e \u003cstrong\u003eethylacetate Plant extract\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e802\u0026thinsp;\u0026plusmn;\u0026thinsp;13.56 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2309\u0026thinsp;\u0026plusmn;\u0026thinsp;4.980 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2706\u0026thinsp;\u0026plusmn;\u0026thinsp;43.58\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Carterii\u003c/strong\u003e \u003cstrong\u003eNSs (P1) (20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e343\u0026thinsp;\u0026plusmn;\u0026thinsp;9.151\u003csup\u003ebcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2566\u0026thinsp;\u0026plusmn;\u0026thinsp;22.44 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2658\u0026thinsp;\u0026plusmn;\u0026thinsp;25.63\u003csup\u003ebc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eB. Carterii\u003c/strong\u003e \u003cstrong\u003eNSs (P2) (20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e858\u0026thinsp;\u0026plusmn;\u0026thinsp;17.61 \u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2847\u0026thinsp;\u0026plusmn;\u0026thinsp;17.24 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2190\u0026thinsp;\u0026plusmn;\u0026thinsp;93.59 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDF1 NSs(20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1295\u0026thinsp;\u0026plusmn;\u0026thinsp;15.61 \u003csup\u003eacd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3550\u0026thinsp;\u0026plusmn;\u0026thinsp;24.36 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3610\u0026thinsp;\u0026plusmn;\u0026thinsp;15.38 \u003csup\u003eacd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDF2 NSs(20 \u0026micro;g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1303\u0026thinsp;\u0026plusmn;\u0026thinsp;8.47 \u003csup\u003eacd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2847\u0026thinsp;\u0026plusmn;\u0026thinsp;17.24 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3460\u0026thinsp;\u0026plusmn;\u0026thinsp;17.86 \u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003eResults are expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E, N\u0026thinsp;=\u0026thinsp;5.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eComparisons between means were carried out using one way analysis of variance (ANOVA) followed by Tukey Kramer\u0026rsquo;s multiple comparisons test. p\u0026thinsp;\u0026le;\u0026thinsp;0.0001.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(a) Significantly different from Negative control group\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(b) Significantly different from positive control group\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(c) Significantly different from Dexa salt group\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(d) Significantly different from Boswellia extract group\u003c/em\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSuccessful extraction and characterization of the ethylacetate plant extract from \u003cem\u003eB. carterii\u003c/em\u003e was achieved. The majority of the desirable characteristics necessary for an adequate dosage form were displayed by Nano sponges loaded with \u003cem\u003eB. carterii\u003c/em\u003e ethylacetate plant extract or Dex salt. Small particle size Nano sponges have been created. Sustained release for up to 24 hours was achieved by the release profiles. Additionally, these Nano sponge formulas have been shown to have a sufficient capacity for extending the time of drug release, which may advantageously result in a reduction in the frequency of drug administration, a decrease in medication dosage, and the avoidance of relatively systemic unwanted adverse effects\u003cem\u003e.\u003c/em\u003e The anti-inflammatory activity of either \u003cem\u003eB. Carterii\u0026nbsp;\u003c/em\u003eethylacetate\u003cem\u003e\u0026nbsp;\u003c/em\u003eplant extract, Dexa salt and their Nano formulations (D1, D5, P1, and P2) in the treatments of respiratory allergies were evaluated\u003cstrong\u003e.\u003c/strong\u003e Histopathologic examinations and measurements of intracellular adhesion molecule-1 (ICAM-1), Leukotriene B\u003csub\u003e4\u003c/sub\u003e (LTB\u003csub\u003e4\u003c/sub\u003e) and Interleukin \u0026beta;4 (IL\u0026beta;4) levels revealed that the treatment significantly lowered the levels of the inflammatory biomarkers in treated rats and exhibited improved histopathologic profiles when compared to the positive control group. \u003cem\u003eBoswellia\u003c/em\u003e ethylacetate extract and its Nano sponge formulation P1 had promising therapeutic effects on upper and lower respiratory diseases. The effect of \u003cem\u003eboswellia\u003c/em\u003e ethylacetate extract formulation P1 may be due to synergism between both the extract and DF1. This effect was achieved by blocking both the ICAM-1 and LTB4 pathways, therefore counteracting the allergic and inflammatory effects of talc powder.\u003c/p\u003e"},{"header":"Abbreviations","content":" \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003eAbbreviation\u003c/div\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eMeaning\u003c/div\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eBC\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eBoswellia carterii\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCID\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eCollision-Induced Dissociation\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eHESI\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eHeated Electrospray Ionization\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eC\u0026thinsp;+\u0026thinsp;ve\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ePositive control group\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDPPH\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2,2-diphenyl-1-picrylhydrazyl\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDEX\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eDexamethasone salt\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eICAM-1\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eIntracellular adhesion molecule-1\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIlβ4\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eInterleukinβ 4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLTB\u003c/span\u003e\u003csub\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003e4\u003c/span\u003e\u003c/sub\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eLeukotriene B4\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCD\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ecyclodextrin\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eCA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003ecitric acid\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eABTS\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003ePMDA\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003epyromellitic dianhydride\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv 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name=\"Emphasis\"\u003eRPM\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eRotations per minute\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eIAEC\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eInstitutional Animal Ethical Committee\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eUPLC\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eUltra-Performance Liquid Chromatography\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eEPI-β-CD\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eEpichlorohydrin-β-cyclodextrin\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eBDE\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003e1,4-Butanediol diglycidyl ether\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eRI\u003c/span\u003e\u003c/div\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cdiv class=\"SimplePara\"\u003eretention indices\u003c/div\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003cbr/\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eBassant MM Ibrahim:\u0026nbsp;\u003c/strong\u003eProject no\u003cstrong\u003e\u0026nbsp;\u0026ldquo;\u003c/strong\u003e12060132\u0026rdquo;\u0026nbsp;PI\u0026nbsp;, Conceptualization, Methodology, Investigation, Data curation, Writing - original draft review \u0026amp; editing\u003cstrong\u003e. Asmaa Badawy Darwish:\u003c/strong\u003e Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Writing - original draft, review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;Sally Abou Taleb:\u0026nbsp;\u003c/strong\u003eConceptualization, Methodology, Investigation, Data curation. \u003cstrong\u003e\u003cem\u003eReda M. Mourad\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConceptualization, \u003cstrong\u003eNoha Nazeeh Yassen\u003c/strong\u003e: \u0026nbsp;Methodology, Investigation, Formal analysis.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cstrong\u003eAlyaa Farouk Hussein:\u003c/strong\u003e Methodology, Investigation, Formal analysis. \u003cstrong\u003eShaimaa Ali Gad:\u003c/strong\u003e Methodology, Investigation, Formal analysis\u003cstrong\u003e\u0026nbsp;Mona A. Mohammed:\u0026nbsp;\u003c/strong\u003eProject no \u0026ldquo;12060132\u0026rdquo; Co-PI, Conceptualization, Methodology, Investigation, Data curation, Writing - original draft, review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e The authors don\u0026rsquo;t have any conflict of interest regarding the current manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study had been funded by the \u0026ldquo;National Research Centre\u0026rdquo; in Egypt, as a part of the project entitled\u003cspan dir=\"RTL\"\u003e:\u003c/span\u003e \u0026ldquo;Pharmacological investigation and Metabolomics study of promising anti-inflammatory herbal oils loaded in a polymeric nano-composite drug delivery system targeting Dermatitis and Upper Respiratory Allergy in rats\u0026rdquo;, under registration number. 12060132.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e As authors of this work, all of us \u0026nbsp;would like to express our great thanks and appreciation to the \u0026ldquo;In house project unit of National Research Centre, Dokki, Egypt\u0026rdquo; for providing a lot of facilities for this work as a part of the project entitled \u0026ldquo;Pharmacological investigation and Metabolomics study of promising anti-inflammatory herbal oils loaded in a polymeric nano-composite drug delivery system targeting Dermatitis and Upper Respiratory Allergy in rats\u0026rdquo;, under registration number 12060132. Also, we would like also to express our deep gratitude and our grateful thanks to \u0026ldquo;Prof. Dr Hab. Piotr Kachlicki; Head of Metabolomics team at Institute of Plant Genetics PAS Poznan\u0026rdquo;, for his great support and appreciated assistance for using the UPLC/HRMS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u0026nbsp;\u003c/strong\u003eThe datasets used during the current study available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWang, Y.-g., et al., \u003cem\u003eBioactive cembrane-type diterpenoids from the gum-resin of Boswellia carterii.\u003c/em\u003e Fitoterapia, 2019. \u003cstrong\u003e137\u003c/strong\u003e: p. 104263.\u003c/li\u003e\n\u003cli\u003eSiddiqui, M.Z., \u003cem\u003eBoswellia serrata, a potential antiinflammatory agent: an overview.\u003c/em\u003e Indian journal of pharmaceutical sciences, 2011. \u003cstrong\u003e73\u003c/strong\u003e(3): p. 255.\u003c/li\u003e\n\u003cli\u003eParsonidis, P., et al., \u003cem\u003eCytotoxic effect of Boswellia sacra on human cancer cell lines.\u003c/em\u003e Journal of Cancer Science \u0026amp; Therapy, 2021. \u003cstrong\u003e13\u003c/strong\u003e(7).\u003c/li\u003e\n\u003cli\u003eAljarari, R., \u003cem\u003eNeuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl 3 induced Alzheimer\u0026apos;s disease in male albino rat.\u003c/em\u003e Brazilian Journal of Biology, 2023. \u003cstrong\u003e83\u003c/strong\u003e: p. e272466.\u003c/li\u003e\n\u003cli\u003eMohammed, M.A., \u003cem\u003eFighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now.\u003c/em\u003e Frontiers in Pharmacology, 2023. \u003cstrong\u003e14\u003c/strong\u003e: p. 1111329.\u003c/li\u003e\n\u003cli\u003eBhakshu, L.M. and K.V. 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Guruprasad, \u003cem\u003eAccidental acute talcum powder inhalation in an adult: a rare case with a short review of literature.\u003c/em\u003e Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine, 2020. \u003cstrong\u003e24\u003c/strong\u003e(6): p. 490.\u003c/li\u003e\n\u003cli\u003eZettl, I., et al., \u003cem\u003eGeneration of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment.\u003c/em\u003e Frontiers in Immunology, 2022. \u003cstrong\u003e13\u003c/strong\u003e: p. 1022418.\u003c/li\u003e\n\u003cli\u003eShukla, S.D., et al., \u003cem\u003eTargeting intercellular adhesion molecule-1 (ICAM-1) to reduce rhinovirus-induced acute exacerbations in chronic respiratory diseases.\u003c/em\u003e Inflammopharmacology, 2022. \u003cstrong\u003e30\u003c/strong\u003e(3): p. 725-735.\u003c/li\u003e\n\u003cli\u003eOkunishi, K. and M. Peters-Golden, \u003cem\u003eLeukotrienes and airway inflammation.\u003c/em\u003e Biochimica et Biophysica Acta (BBA)-General Subjects, 2011. \u003cstrong\u003e1810\u003c/strong\u003e(11): p. 1096-1102.\u003c/li\u003e\n\u003cli\u003eLi, S., et al., \u003cem\u003eRole of interleukin-4 (IL-4) in respiratory infection and allergy caused by early-life Chlamydia infection.\u003c/em\u003e Journal of Microbiology and Biotechnology, 2021. \u003cstrong\u003e31\u003c/strong\u003e(8): p. 1109.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Boswellia Carterri, ethylacetate, Nanosponges, Drug Delivery, Sustained release, respiratory distress","lastPublishedDoi":"10.21203/rs.3.rs-3826210/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3826210/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eBoswellia carterii\u003c/em\u003e (BC) resins plants have a long historical background as a treatment for inflammation, as indicated by information originating from multiple countries. Twenty-seven diterpenoids have been identified in ethylacetate and total methanol BC, comprising seventeen boscartins of the cembrane-type diterpenoids and ten boscartols of the prenylaromadendrane-type diterpenoids. Moreover, twenty-one known triterpenoids have also been found, encompassing nine tirucallane-type, six ursane-type, four oleanane-type, and two lupane-type. The cembrane-type diterpenoids hold a significant position in pharmaceutical chemistry and related industries due to their captivating biological characteristics and promising pharmacological potentials. Extraction of BC, creation and assessment of nano sponges loaded with either \u003cem\u003eB. Carterii\u003c/em\u003e plant extract or DEX, are the subjects of our current investigation. With the use of ultrasound-assisted synthesis, nano sponges were produced. The entrapment efficiency (EE%) of medications in Nano sponges was examined using spectrophotometry. Nano sponges were characterized using a number of methods. Within Nano sponges, the EE% of medicines varied between 98.52± 0.07 and 99.64± 1.40%. The nano sponges' particle sizes varied from 105.9±15.9 to 166.8±26.3 nm. Drugs released from Nano sponges using the Korsmeyer-Peppas concept. In respiratory distressed rats, the effects of BC plant extract, DEX salt and their nano formulations (D1, D5, P1 and P1), were tested. Treatment significantly reduced ICAM-1, LTB4, and ILβ4 levels and improved histopathologic profiles, when compared to the positive control group. \u003cem\u003eBoswellia\u003c/em\u003e extract and its Nano sponge formulation P1 showed promising therapeutic effects. The effect of P1 may be due to synergism between both the extract and the formulation. This effect was achieved by blocking both ICAM-1 and LTB4 pathways, therefore counteracting the effects of talc powder.\u003c/p\u003e","manuscriptTitle":"Effect of enclosing terpenoids-rich Boswellia Carterri ethyl acetate extract in binary cyclodextrin based oligomer nano-complex for improving its activity via counteracting ICAM-1, Ilβ4 and LTB4 pathways in respiratory distressed rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-08 16:02:57","doi":"10.21203/rs.3.rs-3826210/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-04-11T03:56:09+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"81172a7d-3cad-4fc4-a46b-01f8c5b0efb7","date":"2024-03-30T05:49:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-25T10:36:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9aa04390-d55c-4d7d-b104-4cc837e96414","date":"2024-03-06T00:54:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-17T14:48:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-15T04:50:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-01-04T11:31:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-04T11:30:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2023-12-31T16:21:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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