Unravelling the Therapeutic Potential of Aloe vera Phytochemicals as Anti-inflammatory Agents Targeting TNF-α: An In-Silico Approach

Unravelling the Therapeutic Potential of Aloe vera Phytochemicals as Anti-inflammatory Agents Targeting TNF-α: An In-Silico Approach | 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 Research Article Unravelling the Therapeutic Potential of Aloe vera Phytochemicals as Anti-inflammatory Agents Targeting TNF-α: An In-Silico Approach C. Abinaya, J. Suresh, E. Kokiladevi, D. Uma, N. Bharathi, S. T. Bini sundar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4360703/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Rheumatoid arthritis (RA), a debilitating autoimmune disorder, poses a significant global health burden with limited therapeutic options and associated adverse effects. This study pioneered the investigation of Aloe vera phytochemicals as potential anti-inflammatory agents by targeting the pivotal cytokine Tumor Necrosis Factor-alpha (TNF-α), a key mediator of inflammation in RA. Through an integrative in-silico approach, molecular docking analyses evaluated the binding affinities of 74 Aloe vera compounds against TNF-α. Notably, the top-ranking compounds mannan, folacin, and aloesin exhibited superior binding energies compared to approved anti-inflammatory drugs. Subsequent pharmacokinetic and toxicity assessments revealed aloesin as a promising lead-like compound, adhering to drug-likeness criteria with a favorable toxicity profile. These findings position aloesin as a pioneering candidate for further preclinical and clinical investigations, paving the way for the development of novel, safe, and effective anti-inflammatory therapies for RA based on natural products. Aloe vera Anti-inflammatory Molecular docking Aloesin ADMET Pharmacokinetics Figures Figure 1 Figure 2 Introduction Rheumatoid arthritis (RA) is a chronic, progressive, and debilitating autoimmune disorder characterized by persistent inflammation of the synovial joints, leading to cartilage degradation, bone erosion, and functional impairment. The disease affects millions of individuals worldwide, imposing a substantial socioeconomic burden and diminishing the quality of life for patients (Smolen et al., 2016 ). Despite the availability of various treatment options, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents, the management of RA remains a significant challenge. Current therapies are often associated with adverse effects, limited long-term efficacy, and a substantial economic burden, underscoring the need for safer and more cost-effective alternatives (Smolen et al., 2016 ; Babaahmadi et al., 2023 ). Natural products derived from medicinal plants have gained increasing attention as potential sources of novel therapeutic agents due to their structural diversity, potential for multi-target interactions, and generally favorable safety profiles (Harvey et al., 2015 ; Pan et al., 2013 ). Aloe vera, with its rich repertoire of bioactive compounds, presents a promising avenue for the development of anti-inflammatory agents targeting RA, offering potential advantages over synthetic drugs in terms of reduced toxicity and improved patient acceptance (Akev et al., 2015 ). Aloe vera , recognized for its historical significance as the " plant of immortality ," holds profound pharmaceutical importance in both traditional and modern medicine. Its gel, containing a diverse array of bioactive compounds, positions Aloe vera as a versatile candidate for therapeutic applications, particularly in dermatological formulations, wound healing, and anti-inflammatory interventions. The increasing global demand for natural remedies has driven a substantial rise in Aloe vera production and cultivation. Its prevalence spans across arid regions worldwide, contributing significantly to the pharmaceutical and cosmetic industries. Noteworthy cultivation areas include India, Australia, USA, Japan, and Europe, attesting to its economic importance and widespread applications. Inflammation, a pivotal aspect of the body's immune response, is intricately regulated by molecular signalling pathways. Tumour Necrosis Factor (TNF), a key inflammatory protein, plays a key role in initiating and perpetuating inflammatory cascades, implicated in various pathological conditions. Rheumatoid arthritis (RA), a systemic autoimmune disorder, remains a challenge in medical treatment despite current interventions such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), specifically TNF-α inhibitors. Aloe vera , renowned for its medicinal properties, has garnered scientific interest for its potential anti-inflammatory effects (Arunkumar and Muthuselvam, 2009 ; Jalinder et al ., 2022; Kumar et al., 2019 ). Aloe vera 's polysaccharides, phenolic compounds, and sterols have emerged as key players in modulating inflammatory pathways. This study employs an in-silico approach, utilizing molecular docking analyses and pharmacokinetic assessments, to evaluate the inhibitory potential of Aloe phytochemicals against TNF-α. This computational analysis aims to provide insights into the therapeutic efficacy of Aloe vera constituents against TNF-α, offering a foundation for future experimental investigations. Materials and Methods Selection of Phytochemicals in Aloe vera : A curated selection of Aloe vera phytochemicals was undertaken through a comprehensive literature review and utilization of the IMPPAT ( https://cb.imsc.res.in/imppat ) and ZINC databases. Phytochemicals were chosen based on documented presence in the literature and availability within these databases, ensuring a systematic approach aligned with established knowledge. ZINC Database A freely accessible online database for exploring diverse chemical compounds in medicinal chemistry and drug discovery. It provided a comprehensive collection supporting tasks such as virtual screening for potential drug candidates. IMPPAT Database A manually curated database encompassing 1,742 Indian Medicinal Plants, 9,596 Phytochemicals, and 1,124 Therapeutic uses. It included a comprehensive dataset comprising 27,074 plant-phytochemical associations and 11,514 plant-therapeutic associations, offering valuable insights into relationships between medicinal plants, their phytochemical constituents, and therapeutic applications. Selection of Anti-Inflammatory Drugs: Approved anti-inflammatory drugs from the Therapeutic Target Database served as benchmarks for comparing the efficacy of bioactive compounds derived from Aloe vera . This approach aimed to assess the relative effectiveness of Aloe vera compounds against established anti-inflammatory medications. Therapeutic Target Database: A comprehensive resource providing information on molecular targets associated with diseases and their corresponding drugs. It offered details on target proteins, disease associations, drug information, biochemical pathways, pharmacological data, and structural information for researchers engaged in drug discovery and development. Molecular Docking Studies: The primary objective in molecular docking was to accurately gauge the scoring function and assess interactions between proteins and ligands. Autodock Vina, coupled with PyRx, was employed for generating a dataset of bioactive binding poses of ligands within the active site of TNF-alpha. Additionally, the Discovery Studio 2024 Client software was utilized to model nonbonded polar and hydrophobic contacts within the inhibitor site of TNF alpha. Structure Retrieval of Compounds: Three-dimensional structures of bioactive compounds in Aloe vera and over-the-counter medicines recommended for inflammation, such as Aspirin, Hydrocortisone, Melaxicam, Ibuprofen, Celecoxib, and Naproxen, along with the three-dimensional structures of the target protein TNF alpha, were retrieved from databases such as the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) and PubChem. Molecular Docking Software: Molecular docking studies were conducted using Pyrex and Discovery Studio software. - Pyrex : An open-source software tool designed for molecular docking studies, employing an iterative approach for predicting ligand poses within the protein's binding site. - Discovery Studio : A comprehensive molecular modelling and simulation software utilized for studying protein-ligand interactions, integrating various algorithms and scoring functions for accurate prediction of binding affinities. Docking Procedure : - Preparation of Protein : The three-dimensional structure of TNF obtained from RCSB PDB was processed to remove water molecules and optimize hydrogen bonds. - Ligand Preparation : Aloe vera compounds and commercial drug compounds retrieved from PubChem were prepared by assigning correct bond orders and optimizing conformations. Ligands were loaded into PyRx virtual screening software using OpenBabel for conversion to PDB format. Grid Generation Docking was performed using Autodock Vina in PyRx virtual screening software with specific grid parameters. The Lamarckian Genetic Algorithm was employed to generate 10 docked positions for each ligand. Subsequently, docking results were analyzed and visualized based on docking scores using Discovery Studio 2024 Client and PyMol software. Scoring and Analysis: Docking scores, binding efficiency, and hydrogen bond interactions were analyzed to evaluate the strength and specificity of ligand binding. Molecular docking results were thoroughly analyzed for binding affinity, and the most promising Aloe vera compound was selected based on docking scores and hydrogen bond interactions with TNF. Pharmacology Analysis: Pharmacokinetic analysis of ligands was systematically performed using the SwissADME server ( http://www.swissadme.ch/ ). This computational tool facilitated the comprehensive evaluation of various pharmacokinetic parameters, encompassing absorption, metabolism, distribution, excretion, and toxicity predictions for the prospective compounds under investigation. Additionally, the SwissADME server provided insights into critical aspects such as bioavailability score, drugability, and synthetic accessibility score, offering a holistic perspective on the pharmaceutical viability of the examined compounds. Ligands were screened according to Lipinski's Rule of Five for safety assessment in drug development (Patel et al., 2021 ), and toxicology predictions were performed using the pkCSM online server. Parameters analyzed included AMES toxicity, maximum tolerance dose, hERG inhibition, LD50, LOAEL, hepatotoxicity, skin toxicity, T. pyriformis toxicity, and minnow toxicity. This rigorous pharmacological scrutiny aims to inform and guide further exploration of these compounds in drug development endeavours. Results and Discussion The study addresses the considerable socio-economic burden posed by the inflammatory autoimmune disease rheumatoid arthritis, affecting around 1% of the global population (Smolen et al., 2016 ). Acknowledging the limitations of current RA treatments, the research aims to explore alternative therapeutic interventions with reduced side effects. The principal focus is on investigating the potential of phytochemicals to target the cytokine TNF-α, thereby demonstrating their anti-inflammatory activity. In pursuit of identifying active chemical constituents of Aloe vera possessing potential interactions with the TNF alpha protein, molecular docking studies were conducted for a set of 74 Aloe vera chemical constituents. The subsequent identification of top hits is discussed herein. Moreover, our investigation extended to assessing the pharmacokinetics and toxicity properties of molecules exhibiting promising results, positioning them as potential drug candidates. The use of Autodock Vina facilitated the determination of molecular interactions and binding energy between Aloe vera phytoconstituents and TNF alpha protein, contributing valuable insights for drug discovery endeavours. Aloe vera demonstrates anti-inflammatory properties by effectively inhibiting the cyclooxygenase pathway, resulting in a diminished synthesis of prostaglandins and, consequently, a reduction in inflammatory processes (Devaraj and Karpagam, 2011 ; Vijayalakshmi et al., 2012 ). The bioactive compounds in Aloe vera demonstrate an inhibitory effect on the release of pro-inflammatory mediators, such as cytokines and histamine (Arunkumar and Muthuselvam, 2009 ; Jalinder et al ., 2022; Kumar et al., 2019 ). Binding energy is a measure of the affinity in a ligand-protein complex. It represents the difference between the energy of the complex (ligand bound to the protein) and the sum of the energies of each molecule separately (ligand and protein considered as independent entities). In other words, it quantifies the stability and strength of the interaction between the ligand and the protein in a molecular complex. A lower binding energy typically indicates a more favourable and stronger binding interaction (Kastritis and Bonvin, 2013 ). Table 2 displays the binding potential energy or Vina fitness scores resulting from the docking of TNF-α with both approved drugs and Aloe vera compounds. A comparison of the docked binding energies of the best ligands with reference standard drugs indicates that the drugs exhibit lower binding energies than the top 10 ligands. The observed binding affinity values range from − 10 to -9.1 kcal/mol (Table 2 ). Notably, mannan emerges as the highest binding affinity compound, registering − 10 kcal/mol, surpassing folacin, aloesin, beta-sitosterol and other compounds. Analysis of the docking results, the interactions listed in Table 2 reveal that the biochemical compounds in Aloe vera exhibit highly consistent interactions, surpassing aspirin and other drug standards. Consequently, mannan, folacin, and aloesin are identified as the top three most promising inhibitors of TNF-α. Table 1 Characteristics of phytoconstituents of Aloe vera (L) S.No. Ligand PubChem ID Molecular formula Molecular weight (g/mol) 1. 2(3H)-Benzothiazolone 13625 C 7 H 5 NOS 151.19 2. 3,4-Dihydrocoumarin 660 C 9 H 8 O 2 148.16 3. 7-Hydroxy-4-benzopyrone 5409279 C 9 H 6 O 3 162.14 4. 15-Methylhexadecanoic acid 164860 C 17 H 34 O 2 270.5 5. Acemannan 72041 C 66 H 100 NO 49 − 1691.5 6. Allantoin 204 C 4 H 6 N 4 O 3 158.12 7. Aloe emodin 10207 C 15 H 10 O 5 270.24 8. Aloenin 162305 C 19 H 22 O 10 410.4 9. Aloeresin 160190 C 19 H 22 O 9 394.4 10. Aloesone 5317700 C 13 H 12 O 4 232.23 11. Aloin A 12305761 C 21 H 22 O 9 418.4 12. Aloin B 14989 C 21 H 22 O 9 418.4 13. Aluminum 5359268 Al 26.981 14. anthracene 8418 C 14 H 10 178.23 15. anthranol 10731 C 14 H 10 O 194.23 16. Anthraquinone 6780 C 14 H 8 O 2 208.21 17. Ascorbic Acid 54670067 C 6 H 8 O 6 176.12 18. Asparagine 6267 C 4 H 8 N 2 O 3 132.12 19. Aspirin 2244 C 9 H 8 O 4 180.16 20. Auxin 802 C 10 H 9 NO 2 175.18 21. beta carotene 5280489 C 40 H 56 536.9 22. beta sitosterol 222284 C 29 H 50 O 414.7 23. Campesterol 173183 C 28 H 48 O 400.7 24. Carvacrol 10364 C 10 H 14 O 150.22 25. Caryophyllene oxide 1742210 C 15 H 24 O 220.35 26. Caryophyllene 5281515 C 15 H 24 204.35 27. Celecoxib 2662 C 17 H 14 F 3 N 3 O 2 S 381.4 28. Cholesterol 5997 C 27 H 46 O 386.7 29. Chrysophanic acid 10208 C 15 H 10 O 4 254.24 30. chrysophanol 10208 C 15 H 10 O 4 254.24 31. Citric acid 311 C 6 H 8 O 7 192.12 32. Creatinine 588 C 4 H 7 N 3 O 113.12 33. Cycloartenol 92110 C 30 H 50 O 426.7 34. Cysteine hydrochloride 25150 C 3 H 8 ClNO 2 S 157.62 35. Cysteine 5862 C 3 H 7 NO 2 S 121.16 36. D fructose 2723872 C 6 H 12 O 6 180.16 37. D galactonic acid 128869 C 6 H 12 O 7 196.16 38. D galactose 6036 C 6 H 12 O 6 180.16 39. D glucose 5793 C 6 H 12 O 6 180.16 40. D mannose 18950 C 6 H 12 O 6 180.16 41. d Tartaric acid 439655 C 4 H 6 O 6 150.09 42. Danshenxinkun A 149138 C 18 H 16 O 4 296.3 43. Danthron 2950 C 14 H 8 O 4 240.21 44. Docosane 12405 C 22 H 46 310.6 45. elgonica dimer A 21582596 C 36 H 30 O 14 686.6 46. Feralolide 5317333 C 18 H 16 O 7 344.3 47. Folacin 135398658 C 19 H 19 N 7 O 6 441.4 48. Galactomannan 439336 C 18 H 32 O 16 504.4 49. Globulin G 74329879 C 36 H 61 N 7 O 19 895.9 50. Hydrocortisone 5754 C 21 H 30 O 5 362.5 51. Ibuprofen 3672 C 13 H 18 O 2 206.28 52. Isoaloeresin 76332505 C 29 H 32 O 11 556.6 53. kaempferol 5280863 C 15 H 10 O 6 286.24 54. L Arabinose 439195 C 5 H 10 O 5 150.13 55. Leucine 6106 C 6 H 13 NO 2 131.17 56. linalool 6549 C 10 H 18 O 154.25 57. Lophenol 160482 C 28 H 48 O 400.7 58. Lupeol 259846 C 30 H 50 O 426.7 59. Mannan 25147451 C 24 H 42 O 21 666.6 60. Meloxicam 54677470 C 14 H 13 N 3 O 4 S 2 351.4 61. Naproxen 156391 C 14 H 14 O 3 230.26 62. Niacin 938 C 6 H 5 NO 2 123.11 63. Phenylalanine 6140 C 9 H 11 NO 2 165.19 64. Potassium 5462222 K 39.098 65. Proline 145742 C 5 H 9 NO 2 115.13 66. Quercetin 5280343 C 15 H 10 O 7 302.23 67. Rhababerone 12310964 C 15 H 10 O 5 270.24 68. Salicylic acid 338 C 7 H 6 O 3 138.12 69. Serine 5951 C 3 H 7 NO 3 105.09 70. Sorbitol 5780 C 6 H 14 O 6 182.17 71. Spathulenol 92231 C 15 H 24 O 220.35 72. Threonine 6288 C 4 H 9 NO 3 119.12 73. Thymol acetate 68252 C 12 H 16 O 2 192.25 74. Tricosane 12534 C 23 H 48 324.6 Table 2 Molecular Docking Results of Aloe vera Compounds against TNF alpha and the interacting amino acids Compound Name Docking Score (Kcal/mol) Amino acids with hydrogen bonds Amino acids with hydrophobic Interactions Drug references Aspirin -5.6 GLN 102B GLN 102A Celecoxib -7.6 ARG 103B, GLU 104B GLN 102A, GLN 102B, GLN 102C, GLU 104A Hydrocortisone -6.3 ALN 33A, ASN 34A, ARG 82C Ibuprufen -6.5 TYR 115A, SER 99C, CYS 101A PRO 100A Meloxicam -6.3 ARG 103C, GLU 104A, GLU 104B, GLU 104C, GLN 102B, ARG 103A ARG 103B Naproxen -7.1 LYS 65B, LEU 142B PHE 144B Aloe vera Compounds Mannan -10 PRO 100C, GLN 102B, ARG 103B, GLN 102A, PRO 100°, GLU 116B GLU 116C, ARG 103°, GLU 104C, PRO 100B Folacin -9.8 SER 99B, SER 99C GLU 116B, GLN 102A GLN 102C, GLU 116A Aloesin -9.8 ALA 22B, GLY 24B, LYS 65B, ASP 140B - Beta sitosterol -9.6 GLU 116C, LYS 98B ARG 103B Campesterol -9.6 GLU 116B ARG 103B Lophenol -9.4 GLU 116A ARG 103B Galactomannan -9.4 THR 105B, ARG 103B, ARG 103A, GLN 102A, GLN 102B, GLU 104A, GLU 104B GLU 107B Cholesterol -9.3 GLU 116B, LYS 98C ARG 103B, LYS 98B Quercetin -9.1 GLN 102A, PRO 100A, GLU 116C, GLN 102C Kaempferol -9.1 ASN 34A, GLN 125C, THR 7A, LEU 37A LEU 36A In-depth scrutiny of the results highlights that mannan achieves the lowest binding energy (-10 kcal/mol) in complex with 1TNF, presenting the best score among the docked compounds. However, it's important to note that mannan exhibits three violations of Lipinski's rule of five (Table 3 ). Conversely, aloesin, in docking with the main protease, demonstrates an affinity of -9.8 kcal/mol and forms four hydrogen bonds with ALA 22B, GLY 24B, LYS 65B, and ASP 140B. Notably, aloesin complies with Lipinski's rule of five without any violation, emphasizing its favourable drug-like properties. Table 3 Lipinski parameters for dataset from SwissADME Code Compound Molecular weight (Da) Log p HBD HBA Violation Yes/No Solubility Log S(Mol/L) 1 Mannan 666.58 0.53 14 21 3 No Highly soluble 2.5 2 Folacin 441.4 0.04 6 9 2 No Soluble -2.91 3 Aloesin 394.37 0.92 5 9 0 Yes Very soluble -1.53 4 Beta sitosterol 414.71 5.05 1 1 1 Yes Poorly soluble -9.67 5 Campesterol 400.68 4.97 1 1 1 Yes Poorly soluble -9.11 6 Lophenol 400.68 5.06 1 1 1 Yes Poorly soluble -9.02 7 Galactomannan 504.44 0.13 11 16 3 No Highly soluble 1.38 8 Cholesterol 386.65 4.89 1 1 1 Yes Poorly soluble -9.02 9 Quercetin 302.24 1.63 5 7 0 Yes Soluble -3.91 10 Kaempferol 286.24 1.70 4 6 0 Yes Soluble -3.86 The stability of the ligand-receptor complex is attributed to hydrogen bonds formed by OH and C = O groups, with the ligand playing a dual role as acceptor and donor (Matondo et al., 2018 ). This interaction, coupled with dispersion forces (Trujillo and Sánchez-Sanz, 2016 ), π--π interactions (Kasende et al., 2017 ), and hydrophobic interactions (Muya et al., 2019 ), particularly involving polar amino acids, contributes to the overall stability of the complex. Prediction of drug-likeness descriptors and toxicity The selection of potential inhibitors or optimal docked ligands was based on their binding energy, a critical factor in determining their efficacy. However, in the context of drug development, the evaluation of ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties is essential. The assessment of physicochemical properties, a key parameter influencing efficacy, safety, and metabolism, was carried out employing appropriate methodologies, emphasizing the significance of these properties in the drug development and discovery processes (Pires et al., 2015 ; Clark,2005). In evaluating the physicochemical properties using Lipinski's rule of five (RO5), which includes criteria such as molecular mass, hydrogen-bond donors, hydrogen-bond acceptors, and Log P, the results demonstrated that among the top ten ligands, only 3 ligands fully complied with Lipinski's rule. Lipinski's screening serves as a crucial filter in the drug design process, determining the suitability of a compound for further development (Lipinski, 2004 ). The polysaccharides mannan and galactomannan, along with the steroids Campasterol, β-sitosterol, cholesterol, and lophenol, exhibited a noteworthy affinity for TNF-α. However, their potential use as drugs is hindered by a failure to comply with essential pharmacological parameters and a violation of the Lipinski rule of drug-likeness (Daina et al., 2017 ). In contrast, the chromone aloesin, and the flavonoids Quercetin and Kampferol, emerged as promising TNF-α inhibitors. These compounds not only demonstrated high affinity but also met all pharmacological parameters, showing potential for effective drug development. The binding energies of aloesin, Quercetin, and Kampferol were found to be -9.8, -9.1, and − 9.1 kcal/mol, respectively (Table 2 ). Importantly, these compounds adhered to pharmacological rules and displayed lead-like properties, as outlined in Table 3 . This suggests a potential avenue for the development of these phytochemicals into drug molecules specifically targeting the cytokine TNF-α, which is in line with previous studies highlighting the anti-inflammatory properties of these compounds (Deng et al., 2020 ; Loke et al., 2008 ; Barron et al., 2021 ; Yagi and Takeo,2003). Table 4 presents the pharmacokinetic and toxicity properties of the three potential inhibitors: mannan, folacin, and aloesin. The Ames test, assessing mutagenicity, indicates that all three ligands are non-mutagenic. Carcinogenicity in rats (Carcino_Rat) is negative for all ligands, suggesting no carcinogenic potential. None of the ligands are predicted to permeate the blood-brain barrier (BBB non-permeant). Mannan and folacin show hERG I inhibition, indicating a potential risk for cardiac arrhythmia, while aloesin does not inhibit hERG I. All ligands are non-substrates for P-glycoprotein (P-gp S.), suggesting a low likelihood of causing drug interactions related to P-gp. Folacin and aloesin are predicted to have hepatotoxicity, while mannan is not. None of the ligands show skin sensitization. Regarding cytochrome P450 inhibition, all ligands exhibit no inhibitory effects on the assessed isoforms (1A2, 2C19, 2C9, 2D6, 3A4). Overall, these results suggest that aloesin demonstrates a more favourable toxicity profile compared to mannan and folacin, making it a promising candidate for further drug development (Yagi and Takeo, 2003 ). Table 4 Pharmacokinetics and toxicity properties of the three potential inhibitors Ligand Ames_test Carcino_Rat BBB permeant hERG I hERG II P-gp S. Hepatotoxicity Skin sensitization 1A2 2C19 2C9 2D6 3A4 Mannan No Negative No No Yes Yes No No No No No No No Folacin No Negative No No No No Yes No No No No No No Aloesin No Negative No No No No Yes No No No No No No Future Directions: In vitro and in vivo experimental validation: Conduct cell-based assays using inflammatory cell lines (e.g., RAW 264.7 macrophages) to evaluate the inhibitory effects of aloesin, quercetin, and kaempferol on TNF-α production and other inflammatory mediators. Subsequently, preclinical studies using animal models of RA (e.g., collagen-induced arthritis in mice) should be performed to assess the compounds' anti-inflammatory and therapeutic efficacy in vivo. Compound optimization and structure-activity relationship (SAR) studies: Employ medicinal chemistry techniques, such as structural modifications and analog synthesis, to optimize the identified compounds for improved potency, selectivity, and pharmacokinetic properties. SAR analyses will aid in identifying the structural features crucial for biological activity and guide the design of more potent analogs. Preclinical toxicology and pharmacokinetic studies: Perform comprehensive in vivo toxicity studies (e.g., acute and chronic toxicity, genotoxicity, and reproductive toxicity) to establish the safety profiles of the optimized compounds. Pharmacokinetic studies, including absorption, distribution, metabolism, and excretion (ADME) analyses, will provide insights into the compounds' bioavailability and clearance, informing dosing regimens for future clinical trials. Clinical translation: Based on the outcomes of preclinical studies, initiate Phase I clinical trials to evaluate the safety and tolerability of the lead compounds in healthy volunteers, followed by Phase II and Phase III trials to assess their efficacy and effectiveness in patients with rheumatoid arthritis. These trials should be designed in accordance with regulatory guidelines and ethical principles, with careful monitoring of adverse events and clinical outcomes. Conclusion This pioneering study leveraged an integrative in-silico approach to evaluate the anti-inflammatory potential of Aloe vera phytochemicals by targeting the pivotal cytokine TNF-α, a key mediator of inflammation in rheumatoid arthritis. Molecular docking analyses identified promising compounds, such as aloesin, quercetin, and kaempferol, exhibiting high binding affinities for TNF-α. Notably, aloesin emerged as a lead-like compound, adhering to drug-likeness criteria and displaying a favorable toxicity profile. These findings suggest that aloesin holds significant promise as a potential anti-inflammatory agent derived from a natural source, warranting further preclinical and clinical investigations for the development of novel, safe, and effective therapies for rheumatoid arthritis. The exploration of natural compounds from Aloe vera offers a pioneering avenue for addressing the limitations of current treatments and presents an opportunity for the discovery of innovative therapeutic interventions in the field of rheumatology and autoimmune diseases. Declarations Author Contribution C. A wrote the main manuscript text J.S Project administration and review and editing of manuscriptE.K, D.U Supervised the study and reviewed S.T.B Resources and guidanceN.B conceptualization and supervision, validation of manuscriptAll authors reviewed manuscript References Akev, N., Turkay, G., Can, A., Gurel, A., Yildiz, F., Yardibi, H., ... & Uzun, H. (2015). 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Platinum: a database of computationally modelled pharmacology for nucleic acid targets. Nucleic acids research , 43 (D1), D295-D301. Smolen, J. S., Aletaha, D., & McInnes, I. B. (2016). Rheumatoid arthritis. The Lancet , 388 (10055), 2023-2038. Trujillo, C., & Sánchez‐Sanz, G. (2016). A study of π--π stacking interactions and aromaticity in polycyclic aromatic hydrocarbon/ nucleobase complexes. ChemPhysChem , 17 (3), 395-405. Vijayalakshmi, D., Dhandapani, R., Jayaveni, S., Jithendra, P. S., Rose, C., & Mandal, A. B. (2012). In vitro anti inflammatory activity of Aloe vera by down regulation of MMP-9 in peripheral blood mononuclear cells. Journal of ethnopharmacology , 141 (1), 542-546. Yagi, A., & Takeo, S. (2003). Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart. Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan , 123 (7), 517-532. Additional Declarations No competing interests reported. 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Abinaya","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYDACCcYGBsYGCTD78N9/NkCKsfEAsVoYD/CwpYHoBgJawGrATGaglsNgFl4t/LObGxh+7rDI45+R/OCABM95u7Xth4G21NhE47TkzsEGxt4zEsUSN9IMDhhI3E7ediYRqOVYWm4DLj03EhsYeNskEhtuJBgcSDC4nWx2AKiFseEwTi3yQC2Mf4Fa5t9I/3DgQMK5ZLPzD/FrMQBqYQbZsuFGjsHBhgMH7MxuELDFEOiXw7JnJBI3nnlTcJixITnB7AbQlgQ8fpG73f7w4dsddYnzjqdv/szYYGdvdj794YMPNTa4vc8AiwWBBDCVCFaZgEc5AvBDdNoTpXgUjIJRMApGFAAAMCZv0hsVNucAAAAASUVORK5CYII=","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":true,"prefix":"","firstName":"C.","middleName":"","lastName":"Abinaya","suffix":""},{"id":298208766,"identity":"b137e97d-0c2b-4949-a1cf-8c787b3447d7","order_by":1,"name":"J. Suresh","email":"","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"J.","middleName":"","lastName":"Suresh","suffix":""},{"id":298208767,"identity":"e418b555-c762-4a7a-9fad-c4d8d9f3a1e4","order_by":2,"name":"E. Kokiladevi","email":"","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"E.","middleName":"","lastName":"Kokiladevi","suffix":""},{"id":298208768,"identity":"6a3bf5e0-5a01-4636-b1e3-5693c7a8a1ff","order_by":3,"name":"D. Uma","email":"","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"D.","middleName":"","lastName":"Uma","suffix":""},{"id":298208770,"identity":"3363a980-351b-4647-be9d-e5dac49f7701","order_by":4,"name":"N. Bharathi","email":"","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"N.","middleName":"","lastName":"Bharathi","suffix":""},{"id":298208772,"identity":"41f03403-b77c-464f-9d23-f68e99016b91","order_by":5,"name":"S. T. Bini sundar","email":"","orcid":"","institution":"Tamil Nadu Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"T. Bini","lastName":"sundar","suffix":""}],"badges":[],"createdAt":"2024-05-02 18:52:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4360703/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4360703/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56163399,"identity":"5c1ee481-1164-46e7-b4a4-e11f78b909a3","added_by":"auto","created_at":"2024-05-09 10:02:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":59526,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChemical structures of top 10 compounds with high binding affinity derived from \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eAloe vera\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4360703/v1/fbad843fb5509e25b398990e.png"},{"id":56163398,"identity":"84534e6e-9dc3-4449-b019-cd6a505dfd3a","added_by":"auto","created_at":"2024-05-09 10:02:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":189095,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMolecular docking poses of the top-ranked \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eAloe vera\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e compounds (mannan, folacin, and aloesin) bound to the active site of TNF-α; (a)left) H-bonding interactions between the best ligands with TNF α protein target; (b) (right) All types of interactions between the best ligands with TNF α\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4360703/v1/4e039761a1fe2b04e8ae3a18.png"},{"id":56883466,"identity":"b8a73b6e-40a6-4f29-be6c-944d0cda9777","added_by":"auto","created_at":"2024-05-21 17:32:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1313400,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4360703/v1/18ef4b88-3c46-46bf-a985-ea3cc6f6a853.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unravelling the Therapeutic Potential of Aloe vera Phytochemicals as Anti-inflammatory Agents Targeting TNF-α: An In-Silico Approach","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRheumatoid arthritis (RA) is a chronic, progressive, and debilitating autoimmune disorder characterized by persistent inflammation of the synovial joints, leading to cartilage degradation, bone erosion, and functional impairment. The disease affects millions of individuals worldwide, imposing a substantial socioeconomic burden and diminishing the quality of life for patients (Smolen et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite the availability of various treatment options, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents, the management of RA remains a significant challenge. Current therapies are often associated with adverse effects, limited long-term efficacy, and a substantial economic burden, underscoring the need for safer and more cost-effective alternatives (Smolen et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Babaahmadi et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNatural products derived from medicinal plants have gained increasing attention as potential sources of novel therapeutic agents due to their structural diversity, potential for multi-target interactions, and generally favorable safety profiles (Harvey et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Pan et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Aloe vera, with its rich repertoire of bioactive compounds, presents a promising avenue for the development of anti-inflammatory agents targeting RA, offering potential advantages over synthetic drugs in terms of reduced toxicity and improved patient acceptance (Akev et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eAloe vera\u003c/em\u003e, recognized for its historical significance as the \"\u003cem\u003eplant of immortality\u003c/em\u003e,\" holds profound pharmaceutical importance in both traditional and modern medicine. Its gel, containing a diverse array of bioactive compounds, positions \u003cem\u003eAloe vera\u003c/em\u003e as a versatile candidate for therapeutic applications, particularly in dermatological formulations, wound healing, and anti-inflammatory interventions. The increasing global demand for natural remedies has driven a substantial rise in \u003cem\u003eAloe vera\u003c/em\u003e production and cultivation. Its prevalence spans across arid regions worldwide, contributing significantly to the pharmaceutical and cosmetic industries. Noteworthy cultivation areas include India, Australia, USA, Japan, and Europe, attesting to its economic importance and widespread applications.\u003c/p\u003e \u003cp\u003eInflammation, a pivotal aspect of the body's immune response, is intricately regulated by molecular signalling pathways. Tumour Necrosis Factor (TNF), a key inflammatory protein, plays a key role in initiating and perpetuating inflammatory cascades, implicated in various pathological conditions. Rheumatoid arthritis (RA), a systemic autoimmune disorder, remains a challenge in medical treatment despite current interventions such as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), specifically TNF-α inhibitors. \u003cem\u003eAloe vera\u003c/em\u003e, renowned for its medicinal properties, has garnered scientific interest for its potential anti-inflammatory effects (Arunkumar and Muthuselvam, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Jalinder \u003cem\u003eet al\u003c/em\u003e., 2022; Kumar et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cem\u003eAloe vera\u003c/em\u003e's polysaccharides, phenolic compounds, and sterols have emerged as key players in modulating inflammatory pathways. This study employs an in-silico approach, utilizing molecular docking analyses and pharmacokinetic assessments, to evaluate the inhibitory potential of Aloe phytochemicals against TNF-α. This computational analysis aims to provide insights into the therapeutic efficacy of \u003cem\u003eAloe vera\u003c/em\u003e constituents against TNF-α, offering a foundation for future experimental investigations.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eSelection of Phytochemicals in\u003c/strong\u003e \u003cstrong\u003eAloe vera\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eA curated selection of \u003cem\u003eAloe vera\u003c/em\u003e phytochemicals was undertaken through a comprehensive literature review and utilization of the IMPPAT (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cb.imsc.res.in/imppat\u003c/span\u003e\u003c/span\u003e) and ZINC databases. Phytochemicals were chosen based on documented presence in the literature and availability within these databases, ensuring a systematic approach aligned with established knowledge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZINC Database\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA freely accessible online database for exploring diverse chemical compounds in medicinal chemistry and drug discovery. It provided a comprehensive collection supporting tasks such as virtual screening for potential drug candidates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIMPPAT Database\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA manually curated database encompassing 1,742 Indian Medicinal Plants, 9,596 Phytochemicals, and 1,124 Therapeutic uses. It included a comprehensive dataset comprising 27,074 plant-phytochemical associations and 11,514 plant-therapeutic associations, offering valuable insights into relationships between medicinal plants, their phytochemical constituents, and therapeutic applications.\u003c/p\u003e\n\u003ch3\u003eSelection of Anti-Inflammatory Drugs:\u003c/h3\u003e\n\u003cp\u003eApproved anti-inflammatory drugs from the Therapeutic Target Database served as benchmarks for comparing the efficacy of bioactive compounds derived from \u003cem\u003eAloe vera\u003c/em\u003e. This approach aimed to assess the relative effectiveness of \u003cem\u003eAloe vera\u003c/em\u003e compounds against established anti-inflammatory medications.\u003c/p\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eTherapeutic Target Database:\u003c/h2\u003e\n \u003cp\u003eA comprehensive resource providing information on molecular targets associated with diseases and their corresponding drugs. It offered details on target proteins, disease associations, drug information, biochemical pathways, pharmacological data, and structural information for researchers engaged in drug discovery and development.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eMolecular Docking Studies:\u003c/h2\u003e\n \u003cp\u003eThe primary objective in molecular docking was to accurately gauge the scoring function and assess interactions between proteins and ligands. Autodock Vina, coupled with PyRx, was employed for generating a dataset of bioactive binding poses of ligands within the active site of TNF-alpha. Additionally, the Discovery Studio 2024 Client software was utilized to model nonbonded polar and hydrophobic contacts within the inhibitor site of TNF alpha.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eStructure Retrieval of Compounds:\u003c/h2\u003e\n \u003cp\u003eThree-dimensional structures of bioactive compounds in \u003cem\u003eAloe vera\u003c/em\u003e and over-the-counter medicines recommended for inflammation, such as Aspirin, Hydrocortisone, Melaxicam, Ibuprofen, Celecoxib, and Naproxen, along with the three-dimensional structures of the target protein TNF alpha, were retrieved from databases such as the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) and PubChem.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eMolecular Docking Software:\u003c/h2\u003e\n \u003cp\u003eMolecular docking studies were conducted using Pyrex and Discovery Studio software.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e- Pyrex\u003c/strong\u003e: An open-source software tool designed for molecular docking studies, employing an iterative approach for predicting ligand poses within the protein\u0026apos;s binding site.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e- Discovery Studio\u003c/strong\u003e: A comprehensive molecular modelling and simulation software utilized for studying protein-ligand interactions, integrating various algorithms and scoring functions for accurate prediction of binding affinities.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDocking Procedure\u003c/strong\u003e:\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e- Preparation of Protein\u003c/strong\u003e: The three-dimensional structure of TNF obtained from RCSB PDB was processed to remove water molecules and optimize hydrogen bonds.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e- Ligand Preparation\u003c/strong\u003e: \u003cem\u003eAloe vera\u003c/em\u003e compounds and commercial drug compounds retrieved from PubChem were prepared by assigning correct bond orders and optimizing conformations. Ligands were loaded into PyRx virtual screening software using OpenBabel for conversion to PDB format.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGrid Generation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eDocking was performed using Autodock Vina in PyRx virtual screening software with specific grid parameters. The Lamarckian Genetic Algorithm was employed to generate 10 docked positions for each ligand. Subsequently, docking results were analyzed and visualized based on docking scores using Discovery Studio 2024 Client and PyMol software.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eScoring and Analysis:\u003c/h2\u003e\n \u003cp\u003eDocking scores, binding efficiency, and hydrogen bond interactions were analyzed to evaluate the strength and specificity of ligand binding. Molecular docking results were thoroughly analyzed for binding affinity, and the most promising \u003cem\u003eAloe vera\u003c/em\u003e compound was selected based on docking scores and hydrogen bond interactions with TNF.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003ePharmacology Analysis:\u003c/h2\u003e\n \u003cp\u003ePharmacokinetic analysis of ligands was systematically performed using the SwissADME server (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.swissadme.ch/\u003c/span\u003e\u003c/span\u003e). This computational tool facilitated the comprehensive evaluation of various pharmacokinetic parameters, encompassing absorption, metabolism, distribution, excretion, and toxicity predictions for the prospective compounds under investigation. Additionally, the SwissADME server provided insights into critical aspects such as bioavailability score, drugability, and synthetic accessibility score, offering a holistic perspective on the pharmaceutical viability of the examined compounds. Ligands were screened according to Lipinski\u0026apos;s Rule of Five for safety assessment in drug development (Patel et al., \u003cspan class=\"CitationRef\"\u003e2021\u003c/span\u003e), and toxicology predictions were performed using the pkCSM online server. Parameters analyzed included AMES toxicity, maximum tolerance dose, hERG inhibition, LD50, LOAEL, hepatotoxicity, skin toxicity,\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eT. pyriformis\u003c/em\u003e toxicity, and minnow toxicity. This rigorous pharmacological scrutiny aims to inform and guide further exploration of these compounds in drug development endeavours.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eThe study addresses the considerable socio-economic burden posed by the inflammatory autoimmune disease rheumatoid arthritis, affecting around 1% of the global population (Smolen et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Acknowledging the limitations of current RA treatments, the research aims to explore alternative therapeutic interventions with reduced side effects. The principal focus is on investigating the potential of phytochemicals to target the cytokine TNF-α, thereby demonstrating their anti-inflammatory activity.\u003c/p\u003e \u003cp\u003eIn pursuit of identifying active chemical constituents of Aloe vera possessing potential interactions with the TNF alpha protein, molecular docking studies were conducted for a set of 74 Aloe vera chemical constituents. The subsequent identification of top hits is discussed herein. Moreover, our investigation extended to assessing the pharmacokinetics and toxicity properties of molecules exhibiting promising results, positioning them as potential drug candidates. The use of Autodock Vina facilitated the determination of molecular interactions and binding energy between Aloe vera phytoconstituents and TNF alpha protein, contributing valuable insights for drug discovery endeavours. Aloe vera demonstrates anti-inflammatory properties by effectively inhibiting the cyclooxygenase pathway, resulting in a diminished synthesis of prostaglandins and, consequently, a reduction in inflammatory processes (Devaraj and Karpagam, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Vijayalakshmi et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). The bioactive compounds in Aloe vera demonstrate an inhibitory effect on the release of pro-inflammatory mediators, such as cytokines and histamine (Arunkumar and Muthuselvam, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Jalinder \u003cem\u003eet al\u003c/em\u003e., 2022; Kumar et al., \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBinding energy is a measure of the affinity in a ligand-protein complex. It represents the difference between the energy of the complex (ligand bound to the protein) and the sum of the energies of each molecule separately (ligand and protein considered as independent entities). In other words, it quantifies the stability and strength of the interaction between the ligand and the protein in a molecular complex. A lower binding energy typically indicates a more favourable and stronger binding interaction (Kastritis and Bonvin, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e displays the binding potential energy or Vina fitness scores resulting from the docking of TNF-α with both approved drugs and Aloe vera compounds. A comparison of the docked binding energies of the best ligands with reference standard drugs indicates that the drugs exhibit lower binding energies than the top 10 ligands. The observed binding affinity values range from \u0026minus;\u0026thinsp;10 to -9.1 kcal/mol (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Notably, mannan emerges as the highest binding affinity compound, registering \u0026minus;\u0026thinsp;10 kcal/mol, surpassing folacin, aloesin, beta-sitosterol and other compounds. Analysis of the docking results, the interactions listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e reveal that the biochemical compounds in Aloe vera exhibit highly consistent interactions, surpassing aspirin and other drug standards. Consequently, mannan, folacin, and aloesin are identified as the top three most promising inhibitors of TNF-α.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of phytoconstituents of \u003cem\u003eAloe vera\u003c/em\u003e (L)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS.No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePubChem ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMolecular formula\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMolecular weight (g/mol)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3H)-Benzothiazolone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eNOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e151.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,4-Dihydrocoumarin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e660\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e148.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7-Hydroxy-4-benzopyrone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5409279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e162.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15-Methylhexadecanoic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e164860\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e34\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e270.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcemannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e66\u003c/sub\u003eH\u003csub\u003e100\u003c/sub\u003eNO\u003csub\u003e49\u003c/sub\u003e\u003csup\u003e\u0026minus;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1691.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAllantoin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e158.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloe emodin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e270.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloenin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e162305\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eO\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e410.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloeresin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e160190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e394.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloesone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5317700\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e232.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloin A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12305761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e418.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloin B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14989\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e22\u003c/sub\u003eO\u003csub\u003e9\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e418.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAluminum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5359268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eanthracene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e178.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eanthranol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e194.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnthraquinone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e208.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAscorbic Acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54670067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e176.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAsparagine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eN\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e132.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAspirin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e180.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAuxin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e802\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e175.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ebeta carotene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5280489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e40\u003c/sub\u003eH\u003csub\u003e56\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e536.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ebeta sitosterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e222284\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e50\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e414.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCampesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e173183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e400.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCarvacrol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e150.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaryophyllene oxide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1742210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e220.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaryophyllene\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5281515\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e204.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCelecoxib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2662\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e17\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eF\u003csub\u003e3\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e381.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e27\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e386.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChrysophanic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e254.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003echrysophanol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e254.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCitric acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e192.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e32.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e588\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e113.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCycloartenol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e50\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e426.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCysteine hydrochloride\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e3\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eClNO\u003csub\u003e2\u003c/sub\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e157.62\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCysteine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5862\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e3\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003eS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e121.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD fructose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2723872\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e180.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD galactonic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e128869\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e196.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD galactose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e180.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD glucose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5793\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e180.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eD mannose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e12\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e180.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ed Tartaric acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e439655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e150.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDanshenxinkun A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e149138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e296.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e43.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDanthron\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e8\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e240.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e44.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDocosane\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e22\u003c/sub\u003eH\u003csub\u003e46\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e310.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eelgonica dimer A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21582596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e36\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e14\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e686.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFeralolide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5317333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e344.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e47.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFolacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e135398658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e19\u003c/sub\u003eH\u003csub\u003e19\u003c/sub\u003eN\u003csub\u003e7\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e441.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGalactomannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e439336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e18\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eO\u003csub\u003e16\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e504.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlobulin G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74329879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e36\u003c/sub\u003eH\u003csub\u003e61\u003c/sub\u003eN\u003csub\u003e7\u003c/sub\u003eO\u003csub\u003e19\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e895.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydrocortisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5754\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e21\u003c/sub\u003eH\u003csub\u003e30\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e362.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e51.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIbuprofen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e13\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e206.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e52.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIsoaloeresin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e76332505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e29\u003c/sub\u003eH\u003csub\u003e32\u003c/sub\u003eO\u003csub\u003e11\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e556.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e53.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ekaempferol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5280863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e286.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e54.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eL Arabinose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e439195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e5\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e150.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e55.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeucine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e13\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e131.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e56.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003elinalool\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e10\u003c/sub\u003eH\u003csub\u003e18\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e154.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e57.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLophenol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e160482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e28\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e400.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e58.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLupeol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e259846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e30\u003c/sub\u003eH\u003csub\u003e50\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e426.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e59.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25147451\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e24\u003c/sub\u003eH\u003csub\u003e42\u003c/sub\u003eO\u003csub\u003e21\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e666.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMeloxicam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54677470\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e13\u003c/sub\u003eN\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eS\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e351.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e61.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaproxen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e156391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e14\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e230.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e62.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNiacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e938\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e5\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e123.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e63.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhenylalanine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6140\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e9\u003c/sub\u003eH\u003csub\u003e11\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e165.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e64.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePotassium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5462222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e39.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e145742\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e5\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eNO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e115.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e66.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuercetin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5280343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e7\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e302.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e67.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRhababerone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12310964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003eO\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e270.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e68.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSalicylic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e7\u003c/sub\u003eH\u003csub\u003e6\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e138.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e69.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSerine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5951\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e3\u003c/sub\u003eH\u003csub\u003e7\u003c/sub\u003eNO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e105.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSorbitol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e6\u003c/sub\u003eH\u003csub\u003e14\u003c/sub\u003eO\u003csub\u003e6\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e182.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e71.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpathulenol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92231\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e15\u003c/sub\u003eH\u003csub\u003e24\u003c/sub\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e220.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e72.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThreonine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e4\u003c/sub\u003eH\u003csub\u003e9\u003c/sub\u003eNO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e119.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e73.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThymol acetate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68252\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e12\u003c/sub\u003eH\u003csub\u003e16\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e192.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e74.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTricosane\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eC\u003csub\u003e23\u003c/sub\u003eH\u003csub\u003e48\u003c/sub\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e324.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMolecular Docking Results of \u003cem\u003eAloe vera\u003c/em\u003e Compounds against TNF alpha and the interacting amino acids\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompound Name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDocking Score (Kcal/mol)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAmino acids with hydrogen bonds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmino acids with hydrophobic Interactions\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eDrug references\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLN 102B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 102A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCelecoxib\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARG 103B, GLU 104B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 102A, GLN 102B, GLN 102C, GLU 104A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydrocortisone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALN 33A, ASN 34A, ARG 82C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIbuprufen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTYR 115A, SER 99C, CYS 101A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO 100A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeloxicam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eARG 103C, GLU 104A, GLU 104B, GLU 104C, GLN 102B, ARG 103A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 103B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNaproxen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLYS 65B, LEU 142B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePHE 144B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAloe vera\u003c/b\u003e \u003cb\u003eCompounds\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePRO 100C, GLN 102B, ARG 103B, GLN 102A, PRO 100\u0026deg;, GLU 116B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU 116C, ARG 103\u0026deg;, GLU 104C, PRO 100B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSER 99B, SER 99C GLU 116B, GLN 102A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLN 102C, GLU 116A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAloesin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eALA 22B, GLY 24B, LYS 65B, ASP 140B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBeta sitosterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLU 116C, LYS 98B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 103B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCampesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLU 116B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 103B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLophenol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLU 116A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 103B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGalactomannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTHR 105B, ARG 103B, ARG 103A, GLN 102A, GLN 102B, GLU 104A, GLU 104B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU 107B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLU 116B, LYS 98C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG 103B, LYS 98B\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuercetin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGLN 102A, PRO 100A, GLU 116C, GLN 102C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKaempferol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eASN 34A, GLN 125C, THR 7A, LEU 37A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLEU 36A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn-depth scrutiny of the results highlights that mannan achieves the lowest binding energy (-10 kcal/mol) in complex with 1TNF, presenting the best score among the docked compounds. However, it's important to note that mannan exhibits three violations of Lipinski's rule of five (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Conversely, aloesin, in docking with the main protease, demonstrates an affinity of -9.8 kcal/mol and forms four hydrogen bonds with ALA 22B, GLY 24B, LYS 65B, and ASP 140B. Notably, aloesin complies with Lipinski's rule of five without any violation, emphasizing its favourable drug-like properties.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLipinski parameters for dataset from SwissADME\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\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 \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCode\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCompound\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMolecular weight (Da)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLog p\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHBD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHBA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eViolation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes/No\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSolubility\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLog S(Mol/L)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e666.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHighly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFolacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e441.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSoluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-2.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAloesin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e394.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eVery soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-1.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBeta sitosterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e414.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePoorly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-9.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCampesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e400.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePoorly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-9.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLophenol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e400.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePoorly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-9.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGalactomannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e504.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHighly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCholesterol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e386.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePoorly soluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-9.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuercetin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e302.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSoluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-3.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKaempferol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e286.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSoluble\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-3.86\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe stability of the ligand-receptor complex is attributed to hydrogen bonds formed by OH and C\u0026thinsp;=\u0026thinsp;O groups, with the ligand playing a dual role as acceptor and donor (Matondo et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). This interaction, coupled with dispersion forces (Trujillo and S\u0026aacute;nchez-Sanz, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), π--π interactions (Kasende et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), and hydrophobic interactions (Muya et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), particularly involving polar amino acids, contributes to the overall stability of the complex.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrediction of drug-likeness descriptors and toxicity\u003c/h2\u003e \u003cp\u003eThe selection of potential inhibitors or optimal docked ligands was based on their binding energy, a critical factor in determining their efficacy. However, in the context of drug development, the evaluation of ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties is essential. The assessment of physicochemical properties, a key parameter influencing efficacy, safety, and metabolism, was carried out employing appropriate methodologies, emphasizing the significance of these properties in the drug development and discovery processes (Pires et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Clark,2005).\u003c/p\u003e \u003cp\u003eIn evaluating the physicochemical properties using Lipinski's rule of five (RO5), which includes criteria such as molecular mass, hydrogen-bond donors, hydrogen-bond acceptors, and Log P, the results demonstrated that among the top ten ligands, only 3 ligands fully complied with Lipinski's rule. Lipinski's screening serves as a crucial filter in the drug design process, determining the suitability of a compound for further development (Lipinski, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2004\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe polysaccharides mannan and galactomannan, along with the steroids Campasterol, β-sitosterol, cholesterol, and lophenol, exhibited a noteworthy affinity for TNF-α. However, their potential use as drugs is hindered by a failure to comply with essential pharmacological parameters and a violation of the Lipinski rule of drug-likeness (Daina et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn contrast, the chromone aloesin, and the flavonoids Quercetin and Kampferol, emerged as promising TNF-α inhibitors. These compounds not only demonstrated high affinity but also met all pharmacological parameters, showing potential for effective drug development. The binding energies of aloesin, Quercetin, and Kampferol were found to be -9.8, -9.1, and \u0026minus;\u0026thinsp;9.1 kcal/mol, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Importantly, these compounds adhered to pharmacological rules and displayed lead-like properties, as outlined in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. This suggests a potential avenue for the development of these phytochemicals into drug molecules specifically targeting the cytokine TNF-α, which is in line with previous studies highlighting the anti-inflammatory properties of these compounds (Deng et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Loke et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Barron et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Yagi and Takeo,2003).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents the pharmacokinetic and toxicity properties of the three potential inhibitors: mannan, folacin, and aloesin. The Ames test, assessing mutagenicity, indicates that all three ligands are non-mutagenic. Carcinogenicity in rats (Carcino_Rat) is negative for all ligands, suggesting no carcinogenic potential. None of the ligands are predicted to permeate the blood-brain barrier (BBB non-permeant). Mannan and folacin show hERG I inhibition, indicating a potential risk for cardiac arrhythmia, while aloesin does not inhibit hERG I. All ligands are non-substrates for P-glycoprotein (P-gp S.), suggesting a low likelihood of causing drug interactions related to P-gp. Folacin and aloesin are predicted to have hepatotoxicity, while mannan is not. None of the ligands show skin sensitization. Regarding cytochrome P450 inhibition, all ligands exhibit no inhibitory effects on the assessed isoforms (1A2, 2C19, 2C9, 2D6, 3A4). Overall, these results suggest that aloesin demonstrates a more favourable toxicity profile compared to mannan and folacin, making it a promising candidate for further drug development (Yagi and Takeo, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2003\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePharmacokinetics and toxicity properties of the three potential inhibitors\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmes_test\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCarcino_Rat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBBB permeant\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ehERG I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ehERG II\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP-gp S.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHepatotoxicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSkin sensitization\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1A2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2C19\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2C9\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e2D6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e3A4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMannan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFolacin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAloesin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eFuture Directions:\u003c/h2\u003e \u003cp\u003eIn vitro and in vivo experimental validation: Conduct cell-based assays using inflammatory cell lines (e.g., RAW 264.7 macrophages) to evaluate the inhibitory effects of aloesin, quercetin, and kaempferol on TNF-α production and other inflammatory mediators. Subsequently, preclinical studies using animal models of RA (e.g., collagen-induced arthritis in mice) should be performed to assess the compounds' anti-inflammatory and therapeutic efficacy in vivo.\u003c/p\u003e \u003cp\u003eCompound optimization and structure-activity relationship (SAR) studies: Employ medicinal chemistry techniques, such as structural modifications and analog synthesis, to optimize the identified compounds for improved potency, selectivity, and pharmacokinetic properties. SAR analyses will aid in identifying the structural features crucial for biological activity and guide the design of more potent analogs.\u003c/p\u003e \u003cp\u003ePreclinical toxicology and pharmacokinetic studies: Perform comprehensive in vivo toxicity studies (e.g., acute and chronic toxicity, genotoxicity, and reproductive toxicity) to establish the safety profiles of the optimized compounds. Pharmacokinetic studies, including absorption, distribution, metabolism, and excretion (ADME) analyses, will provide insights into the compounds' bioavailability and clearance, informing dosing regimens for future clinical trials.\u003c/p\u003e \u003cp\u003eClinical translation: Based on the outcomes of preclinical studies, initiate Phase I clinical trials to evaluate the safety and tolerability of the lead compounds in healthy volunteers, followed by Phase II and Phase III trials to assess their efficacy and effectiveness in patients with rheumatoid arthritis. These trials should be designed in accordance with regulatory guidelines and ethical principles, with careful monitoring of adverse events and clinical outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis pioneering study leveraged an integrative in-silico approach to evaluate the anti-inflammatory potential of \u003cem\u003eAloe vera\u003c/em\u003e phytochemicals by targeting the pivotal cytokine TNF-α, a key mediator of inflammation in rheumatoid arthritis. Molecular docking analyses identified promising compounds, such as aloesin, quercetin, and kaempferol, exhibiting high binding affinities for TNF-α. Notably, aloesin emerged as a lead-like compound, adhering to drug-likeness criteria and displaying a favorable toxicity profile. These findings suggest that aloesin holds significant promise as a potential anti-inflammatory agent derived from a natural source, warranting further preclinical and clinical investigations for the development of novel, safe, and effective therapies for rheumatoid arthritis. The exploration of natural compounds from \u003cem\u003eAloe vera\u003c/em\u003e offers a pioneering avenue for addressing the limitations of current treatments and presents an opportunity for the discovery of innovative therapeutic interventions in the field of rheumatology and autoimmune diseases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC. A wrote the main manuscript text J.S Project administration and review and editing of manuscriptE.K, D.U Supervised the study and reviewed S.T.B Resources and guidanceN.B conceptualization and supervision, validation of manuscriptAll authors reviewed manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAkev, N., Turkay, G., Can, A., Gurel, A., Yildiz, F., Yardibi, H., ... \u0026amp; Uzun, H. (2015). Tumour preventive effect of Aloe vera leaf pulp lectin (Aloctin I) on Ehrlich ascites tumours in mice. \u003cem\u003ePhytotherapy Research\u003c/em\u003e, \u003cem\u003e29\u003c/em\u003e(3), 447-452.\u003c/li\u003e\n \u003cli\u003eArunkumar, S., \u0026amp; Muthuselvam, M. (2009). Analysis of phytochemical constituents and antimicrobial activities of Aloe vera L. against clinical pathogens. \u003cem\u003eWorld J Agric Sci\u003c/em\u003e, \u003cem\u003e5\u003c/em\u003e(5), 572-576.\u003c/li\u003e\n \u003cli\u003eBabaahmadi, M., Tayebi, B., Gholipour, N. 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Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart. \u003cem\u003eYakugaku Zasshi: Journal of the Pharmaceutical Society of Japan\u003c/em\u003e, \u003cem\u003e123\u003c/em\u003e(7), 517-532.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Aloe vera, Anti-inflammatory, Molecular docking, Aloesin, ADMET, Pharmacokinetics","lastPublishedDoi":"10.21203/rs.3.rs-4360703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4360703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRheumatoid arthritis (RA), a debilitating autoimmune disorder, poses a significant global health burden with limited therapeutic options and associated adverse effects. This study pioneered the investigation of \u003cem\u003eAloe vera\u003c/em\u003e phytochemicals as potential anti-inflammatory agents by targeting the pivotal cytokine Tumor Necrosis Factor-alpha (TNF-α), a key mediator of inflammation in RA. Through an integrative in-silico approach, molecular docking analyses evaluated the binding affinities of 74 \u003cem\u003eAloe vera\u003c/em\u003ecompounds against TNF-α. Notably, the top-ranking compounds mannan, folacin, and aloesin exhibited superior binding energies compared to approved anti-inflammatory drugs. Subsequent pharmacokinetic and toxicity assessments revealed aloesin as a promising lead-like compound, adhering to drug-likeness criteria with a favorable toxicity profile. These findings position aloesin as a pioneering candidate for further preclinical and clinical investigations, paving the way for the development of novel, safe, and effective anti-inflammatory therapies for RA based on natural products.\u003c/p\u003e","manuscriptTitle":"Unravelling the Therapeutic Potential of Aloe vera Phytochemicals as Anti-inflammatory Agents Targeting TNF-α: An In-Silico Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 10:02:23","doi":"10.21203/rs.3.rs-4360703/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e11206e-085e-46b8-ad96-223600d84fc5","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-21T17:24:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 10:02:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4360703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4360703","identity":"rs-4360703","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}