Ameliorative Effects of Aqueous Extract of Colocasia esculenta Leaf Against Lipopolysaccharide-Induced Prefrontal cortex damage in Mice

Ameliorative Effects of Aqueous Extract of Colocasia esculenta Leaf Against Lipopolysaccharide-Induced Prefrontal cortex damage in Mice | 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 Ameliorative Effects of Aqueous Extract of Colocasia esculenta Leaf Against Lipopolysaccharide-Induced Prefrontal cortex damage in Mice Jacob Adewale Siyanbade, Kingsley Afoke Iteire, Sunday Aderemi Adelakun, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4308560/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background The prefrontal-cortex (PFC) occupies about one-third of the total area of the cerebral cortex and it plays crucial role in Cognition and memory. This study evaluated the ameliorative effects of aqueous extract of Colocasia esculenta leaf (AECEL) on lipopolysaccharide-induced Prefrontal-cortex damage. Methods 42 Swiss male albino mice with weights ranging between 18 − 22g were randomized into six-groups. Group-A consisted of healthy-mice and LPS-induction in groups (B-F) was done by intraperitoneal injections of 0.5mg/kg of lipopolysaccharide (LPS) for seven days. Group-B received distilled-water; Group C- E was treated with AECEL at 400 mg/kg, 600 mg/kg and 800 mg/kg respectively, while Group F received 2.5 mg/kg of donepezil (DPZ) via oral-gavage for 28days. Results Significant increase in the brain oxidative-stress parameters was seen in the LPS-exposed groups compared to the control group (p < 0.05). However, compared with those in the LPS-only group, the levels of oxidative-stress parameters as well as Tumour-necrosis factor-α and interleukin-6 in the brain of AECEL-and DPZ-treated groups were significantly lower (p < 0.05). In the Y-maze test: the percentage-alternation (%ALTERN) significantly decreased (p < 0.05) in the LPS-only group compared to that in the control-group, but there was a significant increase in the %ALTERN in the AECEL-treated groups compared to that in the LPS-only and LPS + DPZ treatment groups (p < 0.05). Bielschowsky staining revealed that the LPS-only group exhibited senile-plaques and neurofibrillary-tangles. Conclusion LPS caused damage to the PFC; AECEL significantly improved cognitive function, memory, and anxiety-like behaviours. Colocasia esculenta Donepezil Lipopolysaccharide Prefrontal-cortex Highlights Intraperitoneal administration of Lipopolysaccharide induced damages to the Prefrontal Cortex of mouse Aqueous extract of Colocasia esculenta leaf exhibited antioxidant property Aqueous extract of Colocasia esculenta leaf ameliorated pathological changes in the Prefrontal cortex. Aqueous extract of Colocasia esculenta leaf has therapeutic potential of mitigating Alzheimer’s disease-like pathology and preserving brain morphology. Aqueous extract of Colocasia esculenta leaf improved cognitive function. 1. Background The brain is composed of million folds of interconnected cells; the neurons are the most important cells in the brain and any disruptions in these connections lead to brain pathologies, particularly neurodegenerative diseases (NDs) [ 1 ]. Alzheimer’s disease (AD) is the commonest neurodegenerative disease making up to72% of dementia cases and affects over 50 million people worldwide. Its incidence in developing countries has been predicted to increase significantly by 2050 [ 2 ]. Many factors contribute to Alzheimer’s disease (AD) of which neuroinflammation, oxidative stress, and vascular dysfunctions have been implicated as key factors. Microbial virulence factors, including lipopolysaccharides (LPS), are associated neuroinflammation [ 3 ]. LPSs have been linked to increased Aβ production and tau proteins, whose levels are always elevated in the brain of Alzheimer’s disease (AD) patients [ 4 ]. Prefrontal cortex plays spectacular roles in cognition and dementia [ 5 ] and recent studies have significantly increased our understanding of the crucial roles it plays in memory tasks [ 6 ]. Medicinal plants and their extracts have shown diverse biological activities, making them valuable alternative therapies. A systematic approach to evaluating plant products, rooted in phytomedicine, is crucial for the ideal development of new drugs from plants and one of such plants is the Colocasia esculent Linn leaf. Colocasia esculenta (CE), Linn (Family: Araceae), commonly known as Taro , has been used traditionally for treating different medical conditions [ 7 ]. Some of the implicated phytoconstituents of the leaf include but are not limited to; β-sitosterol, steroids and flavonoids [ 8 ]. However, limited information exists on its neuroprotective and neuromodulatory properties [ 9 ]. The current research aimed to assess these aspects, recognizing the sparse data on neuromodulatory effects of AECEL in phytomedicine. 2.0. Methods 2.1. Chemical and reagents Commercial kits and reagents for enzyme activity (AChE assay) and protein analysis (ELISA) were purchased from Randox Laboratories Limited (Co Antrim, United Kingdom) and e-bioscience (Inc., San Diego., USA), respectively. Buffers, chemicals, and histological reagents were obtained from Boston Bioproducts, and Sigma-Aldrich Chemical Co ((St. Louis, MO USA). Lipopolysaccharide (5mg of LPS) was gotten from Sigma-Aldrich, USA and donepezil tablets were procured from and Uche Care Pharmacy Ltd, Ondo, Nigeria. 2.2. Collection and Preparation of Crude AECEL Fresh Colocasia leaves were harvested from a farm settlement and authenticated with the voucher specimen LHO 840 at the University Department of Botany Herbarium. Colocasia esculenta leaves were washed and subjected to a moderated drying process. The dried leaves were ground into powder form utilizing a grinding machine, (600g) and soaked in distilled water for 48 hours (2 days). Filtration through muslin cloth was conducted to eliminate insoluble particles and impurities. The resultant solution was filtered using Whatman filter paper (No. 1), and the filtrate was concentrated with a rotary evaporator at 20–28°C. The concentrated crude aqueous extract was stored at a temperature of 4 ± 2°C before being reconstituted for administration [ 10 ]. 2.3. Source of Animals Forty-two (42) healthy adult (aged: 6-8weeks) Swiss male albino mice with body weights ranging between 18 − 22g were purchased from the University of Medical Science breeding colony. All the mice were housed in temperature-controlled plastic cages. A 12 − hour light − dark cycle was maintained with lights on at 7:00 a.m and food (grower marsh - pellets) and water were provided ad libitum. All the mice were subjected to a 14-day period of acclimatization and all protocols followed the guidelines of the research and ethical committee of the University with index number (UNIMED-AREC/Apv/2023/039). 2.4. LPS-induction The mice were treated with intraperitoneal (IP) injections of 0.5 mg/kg of LPS (E. coli O111:B4, Sigma-Aldrich, USA) for seven consecutive days to induce PFC-damage. LPS was prepared using the protocol outlined by Ramírez et al. (2019) [ 11 ]. 2.5. Treatment protocol Treatment was commenced 48 hours after the induction, for 28 consecutive days following this order of administration; the animals were divided into six groups (Groups A, B, C, D, E, F) Group A (normal control) received distilled water (0.2ml/kg b.w) as a placebo throughout the treatment period. Group B (negative control), the LPS-induced model group, was orally administered distilled water only (0.2ml/kg b.w). Groups C, D, and E, which represent LPS-induced models, received oral AECEL at doses of 400mg/kg/day, 600mg/kg/day, and 800mg/kg/day, respectively. Group F (positive control) consisted of LPS-induced model mice that received oral donepezil (DPZ) at a dose of 2.5mg/kg/day. All the groups were treated once daily under the same housing conditions for a period of 28 days and daily animal weight measurement was ensured using a sensitive weighing scale (Infitek, USA). The LD50 of AECEL has been estimated to be about 4000mg/kg by Nyonseu- Nzebang et al (2018) [ 12 ]. 2.6. Neurobehavioral tests Neurobehavioral tests, including Y-Maze, and novel object recognition tests, were carried out to assess lipopolysaccharide-induced neurotoxicity, as well as the ability of AECEL to mitigate neurodegeneration across experimental groups. The assessment was performed before LPS-induction; 24hours post LPS-induction, 14th day of AECEL- treatment and 28th day of AECEL-treatment. 2.7. Sample preparation The animals were sacrificed 24hours post treatment via cervical dislocation. The brains were removed and placed immediately in ice-cold isotonic saline and stored in a freezer. Later the prefrontal cortex was dissected and minced into small pieces, and then homogenized with ten volumes of phosphate buffer (0.1mol/L, PH = 7.4) using a WiseTis® (HG-15A) homogenizer. The homogenates were subsequently centrifuged at 13,000 rpm for 10 min and the resulted supernatant was used for the estimation of antioxidant parameters such as reduced Glutathione (GSH), glutathione peroxidise (Gpx), Superoxide dismutase (SOD), Glutamate dehydrogenase (DGH) and Malondialdehyde (MDA). 2.8. Histological analysis The brain tissues were fixed for 48 hours in 10% neutral buffered formalin. Coronal sections of the prefrontal cortex were obtained and the tissue was preserved in 10% neutral buffered formalin and Paraffin wax-embedded blocks for H&E staining were made. Haematoxylin-eosin (H&E) and Bielschowsky staining procedures were performed on the tissue samples. 2.9. Determination of Malondialdehyde (MDA) and Glutathione peroxidise (Gpx) Activity assay This was carried out by the Varshney and Kale (1990) procedure [ 13 ] and MDA level was calculated using the method of Adam-Vizi and Seregi (1982) [ 14 ]. And GPx estimation was done according to the method of Rotruck and colleagues (1973) [ 15 ]. 2.10. Determination of reduced Glutathione (GSH) and Superoxide dismutase (SOD) activity Reduced glutathione assay was done using the protocol of Moron et al. (1979) [ 16 ]. And SOD activity was determined using the method of Misra and Fridovich (1972) [ 17 ]. 2.12. Determination of Glutamate Dehydrogenase (GDH) GDH activity assay was done using the method described by Strecker (1953) [ 18 ]. 2.13. Neuroinflammatory markers For TNF-α; Elisa kit was used and the assay employs the quantitative sandwich enzyme immunoassay technique. While for the determination of Interleukin-6, the kit uses Sandwich-ELISA principle. 2.14. Statistical Analysis The results were reported as the mean and standard error of the mean (mean ± S.E.M). GraphPad 9 Software (San Diego, USA) was used to analyse the numbers and evaluate the significant differences; comparisons of means between two experimental groups were made using one-way ANOVA with the Newman-Keuls multiple comparison significant difference test and differences were considered significant at p < 0.05. 3.0 Results 3.1. Effect of AECEL on the Y-maze test in LPS-induced neuroinflammation This study revealed a significant reduction (p < 0.05) in the percentage alternation (%ALTERN) in the LPS-only treated group (Group B) compared to that in Group A. Conversely, groups treated with AECEL (Groups C, D & E) exhibited a significant dose-dependent increase in %ALTERN [Figure 1 ], surpassing Group A and the LPS + DPZ (Group F) treatment groups (p < 0.05). 3.2. Effect of AECEL on LPS-induced behavioural in the Novel Object Recognition Test The time spent with the familiar object (TWFO) significantly increased, while the time spent with the novel object (TWNO) decreased in the LPS-exposed group compared to group A (p < 0.05). However, in the LPS + 400 mg AECEL, LPS + 600 mg AECEL, and LPS + 800 mg AECEL treatment groups, TWFO decreased, and TWNO increased significantly compared to both group A and LPS + DPZ group (p < 0.05) [Figure 2 ]. Compared with those in the other treatment groups, TWNO in group A and LPS + DPZ group significantly increased. These findings suggest that AECEL treatment, particularly at a 400 mg/kg bw dose, may have a significant impact on the cognitive aspects of mice affected by LPS exposure. 3.4. Effect of AECEL treatment on oxidative stress and antioxidant parameters The study revealed a significant increase in brain MDA level in mice exposed to LPS (p < 0.05), but posttreatment with AECEL and DPZ resulted in a significant decrease compared to group B (p < 0.05). Interestingly, the LPS + 600mg AECEL and LPS + 800mg AECEL treatments had nonsignificantly lower values than the LPS + 400mg AECEL treatment (p < 0.05). The LPS + 400 mg AECEL, LPS + 600mg AECEL and LPS + 800 mg AECEL treatment groups had significantly greater values than the LPS + DPZ treatment group (p < 0.05) [Table 1 ]. Table 1 Effect of AECEL on LPS-induced oxidative stress Treatment groups Parameters MDA (nmol/g tissue) (Mean ± S.E.M) GDH (nmol/g tissue) (Mean ± S.E.M) SOD (nmol/g tissue) (Mean ± S.E.M) GPx (nmol/g tissue) (Mean ± S.E.M) GSH (nmol/gtissue) (Mean ± S.E.M) A: Control 34.48 ± 2.78 15.90 ± 2.42 40.69 ± 2.95 1.86 ± 0.10 1.41 ± 0.12 B: LPS 75.08 ± 6.10* 3.69 ± 0.91* 11.55 ± 0.97* 0.75 ± 0.07* 0.87 ± 0.08* C:LPS + 400mgCE 54.46 ± 2.57 a 12.67 ± 1.88 αβ 19.19 ± 2.75 αβ 1.44 ± 0.55 αβ 1.12 ± 0.06 αβ D:LPS + 600mgCE 56.75 ± 0.94 αβ 9.91 ± 1.19 αβ 23.63 ± 2.38 αβ 1.20 ± 0.08 αβ 1.04 ± 0.03 αβ E:LPS + 800mgCE 65.79 ± 3.72 αβ 7.60 ± 1.04 αβ 19.55 ± 1.29 αβ 1.09 ± 0.10 αβ 1.01 ± 0.04 αβ F:LPS + DPZ 42.02 ± 3.32 α 14.75 ± 2.27 α 35.36 ± 1.48 α 1.67 ± 0.09 α 1.35 ± 0.06 α The data are expressed as the mean ± S.E.M, n = 10 in each group, *: represents a significant difference from the control, α: represents a significant difference from LPS, β: represents a significant difference from DPZ (p < 0.05), one-way ANOVA followed by Tukey’s post hoc test. Table 2 Effect of AECEL on LPS-induced Neuroinflammation Treatment groups Inflammatory parameters IL-6 (pg/ml) TNF-α (pg/ml) A: Control 86.92 ± 29.36 49.46 ± 7.37 B: LPS 265.00 ± 14.30* 130.50 ± 8.60* C: LPS + 400 mg CE 163.70 ± 9.34 αβ 92.68 ± 7.00 αβ D: LPS + 600 mg CE 181.20 ± 26.24 αβ 95.86 ± 9.17 αβ E: LPS + 800 mg CE 185.90 ± 16.34 αβ 101.90 ± 11.07 αβ F: LPS + DPZ 86.57 ± 6.91 α 64.02 ± 3.75 α The data are expressed as the mean ± S.E.M, n = 10 in each group, *: represents a significant difference from the control, α: represents a significant difference from LPS, β: represents a significant difference from DPZ (p < 0.05), one-way ANOVA followed by Tukey’s post hoc test. The brain SOD, GPx, and GSH quantities were significantly reduced in the LPS-exposed group than in group A (p < 0.05), but compared with LPS treatment alone, AECEL treatment significantly increased the levels of these antioxidant enzymes levels (p < 0.05). Notably, the values in the LPS + DPZ treatment group were significantly greater than in LPS + 400mg AECEL, LPS + 600mg AECEL, and LPS + 800mg AECEL groups (p < 0.05) [Table 1 ]. These findings suggest that AECEL treatment can reverse LPS-induced oxidative-stress, as indicated by the modulation of MDA, SOD, GPx, and GSH levels. 3.5. Effect of AECEL treatment on inflammatory makers In mice exposed to LPS, there was a significant increase (p < 0.05) in IL-6 and TNF-α levels. However, treatment with AECEL resulted in a significant decrease in elevated brain IL-6 and TNF-α levels compared to those in LPS-only group and DPZ-treated mice (p 0.05). These findings suggest that AECEL administration effectively reduces inflammatory markers in LPS-only exposed mice in a dose-dependent manner. 3.6. Haematoxylin and Eosin staining of the Prefrontal cortex of experimental mice Plate 1a,b , Representative photomicrographs of a coronal section of H and E stained prefrontal morphology of the experimental mice showed the Pia Matter ( black arrow ), the Cortical Layer ( CL ), Blood capillaries ( bc ) and the White Matter ( wm ) Control The prefrontal cortex isfilled with well stained neuronal cells ( green arrows ), with no apparent alterations in histoarchitecture. LPS-only: The prefrontal cortex showed signs of degenerative changes in the neurons and numerous cellular degenerations, as indicated by poorly stained nuclei ( green arrows ), cytoplasmic vacuolation ( red arrows ), irregular shapes of some neuroglial cells ( yellow arrows ), and pyknotic nuclei in some cells ( blue arrows). LPS + 400mg AECEL: The prefrontal cortex showed moderate degeneration of neuronal cells ( green arrows ) with cytoplasmic vacuolation ( red arrows ), and the stroma appeared normal. LPS + 600mg AECEL: The prefrontal cortex showed normal laminae and pyramidal neuronal cells ( green arrows ), and the stroma appeared normal. LPS + 800mg AECEL: The prefrontal cortex sections of the animals showed a proper and normal layout of cortical neuronal cells ( green arrows ) from the outermost molecular layer to the innermost multiform layer, with slight dilation ( red arrow ). LPS + DPZ: Several normal neuronal cells ( green arrows ) exhibited cytoplasmic vacuolation ( red arrows ), and the stroma appeared normal. These findings imply that the plant extract, particularly at higher doses, may mitigate degenerative changes in the prefrontal cortex, emphasizing its potential therapeutic effects. 3.7. Bielschowsky silver staining of the Prefrontal cortex of experimental mice Plate 2 Bielschowsky silver staining of the experimental groups after treatment with LPS + 400mg AECEL, LPS + 600mg AECEL, LPS + 800mg AECEL, or LPS + DPZ revealed neuritic plaques ( red arrows ) Dissolutions (d), argyrophilic structures ( yellow arrows ) and fibrillary amyloid deposits (f) were absent in the control group, but were present to varying degrees in the other groups. These results suggest that the administration of the plant extract and donepezil may influence the presence of these neurodegenerative markers, indicating a potential impact on Alzheimer's disease-like pathology. 4.0. Discussion The Y-maze test which measures the frequency of alternations, serves as an indicator of cognitive function in rodents [ 19 ]. Prior to LPS-induction (day 0), the mice showed no memory or cognitive deficits. After exposure to LPS, there was a significant decrease in alternation frequency, indicating reduced locomotive ability, consistent with findings on LPS-induced hypolocomotion behavior in mice by Lucas et al., (2015) [ 20 ]. Posttreatment with varying doses of AECEL (400, 600, and 800mg/kg bw) alleviated the cognitive deficits induced by LPS. Notably, the alternation frequency was greatest in the LPS + 400mg AECEL/kg bw group, suggesting that AECEL has the potential to improve cognitive function in LPS-treated mice, with the 400 mg/kgbw dose showing the most significant improvement. Novel Object Recognition test assessed memory functions and preferences for new objects in the experimental mice. Following AECEL administration, mice in the LPS-only group showed a preference for the familiar object, spending more time with it than the novel objects when compared with the animals in group A, LPS + DPZ, and AECEL treated groups. Conversely, treatment with AECEL (400, 600, and 800 mg/kgbw) exhibited better preference for the novel object, indicating improved recognition memory compared to that of the LPS-only group. This finding aligns with the findings of Meng et al., (2023) [ 21 ] who reported that the ability to perceive novel objects was reduced by LPS injection in mice, which improved with Paeoniflorin treatment. Notably, the 400 mg/kgbw AECEL group showed greater preference for the novel object than the groups treated with the other doses (600 and 800 mg/kgbw). The observed preferences suggest that AECEL has the potential to enhance recognition memory in LPS-injected animals, making it a potential treatment for dementia and related diseases. Reactive oxygen species (ROS) can induce reversible or irreversible changes in enzymes and proteins. Glutathione (GSH), a crucial antioxidant, neutralizes cellular H2O2, O2, and lipid hydroperoxides [ 22 ]. In this study, mice treated with LPS alone exhibited increased malondialdehyde (MDA) levels, indicating elevated oxidative stress, and reduced levels of glutamate dehydrogenase (GDH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH), suggesting impaired antioxidant defenses. Treatment with various doses of AECEL (400, 600, and 800 mg/kg bw) significantly decreased the MDA levels and increased the activities of GDH, SOD, GPx, and GSH compared to those in the LPS-only group. This finding suggests that AECEL has potential to mitigate LPS-induced oxidative stress in animals, which is relevant to other disease models. Notably, the 400 mg/kg group showed significant mitigation of oxidative stress compared to the other treatment groups, with the LPS + 800 mg/kg group showing a similar effect. This study aligns with the results of Kesherwani et al., 2021 [ 23 ] who reported that Euglena tuba extract effectively halted the generation of free radical and increase the level of inflammatory cytokines in an LPS-induced mouse model. Compared with those of control animals, LPS-treated animals exhibited elevated inflammatory cytokine production. Treating LPS with AECEL (400–800 mg/kgbw) significantly reduced cytokine levels, similar to the effects of DPZ in the LPS + DPZ groups. This finding suggests that AECEL has anti-inflammatory properties and is potentially therapeutic for dementia-induced neurological inflammation. Kesherwani et al. (2021) [ 23 ] reported comparable findings for Euglena tuba extract, indicating its efficacy in countering free radicals and increasing inflammatory cytokines in an LPS-induced mouse model. From the Haematoxylin and Eosin Staining of the prefrontal cortex (Plate 1), the control group's normalcy in histoarchitecture and well-preserved neuronal and non-neuronal cell nuclei serves as a baseline for healthy prefrontal cortex morphology. In contrast, the LPS-only group displayed substantial degenerative changes, including poorly stained nuclei, cytoplasmic vacuolation, irregularly shaped neuroglial cells, and pyknotic nuclei. These pathological alterations are characteristic of Alzheimer's disease and reflect severe neuronal damage. The LPS + 400mg AECEL group showed moderate degeneration of neuronal cells and cytoplasmic vacuolation, although the stroma appeared normal. In the LPS + 600mg AECEL group, the prefrontal cortex exhibited normal laminae and well-shaped pyramidal neuronal cells, with a healthy stroma. The most significant improvement was observed in the LPS + 800mg AECEL group, where a proper and normal layout of cortical neuronal cells was evident, with only slight dilation noted (Plate 1). Standard treatment group, LPS + DPZ, showed some improvement with several normal neuronal cells but still exhibited cytoplasmic vacuolation. The results showed that AECEL has a beneficial effect on preserving the prefrontal cortex morphology and reducing Alzheimer's disease-related changes. Bielschowsky silver staining consolidated the H&E stain observations; neuritic plaques ( red arrows ) Dissolutions (d), argyrophilic structures ( yellow arrows ) and fibrillary amyloid deposits (f) were absent in the control group, but were present at varying degrees in all the treatment groups. The findings suggest that administration of the plant extract and donepezil may influence the presence of these neurodegenerative markers, indicating a potential impact on Alzheimer's disease-like pathology. These results showed that AECEL plays a pivotal role in preserving the health of the prefrontal cortex and ameliorating Alzheimer’s disease-related changes although the corresponding histomorphological dose effect has not been established as various structures and signs of improvement were detected across the different doses. These results are similar to the previously reported results of Alagan et al., (2019) [ 24 ] who reported that the administration of Phyllanthus amarus extract effectively protected mice from LPS-induced memory impairment. 4.1. Conclusion The administration of lipopolysaccharide (LPS) to mice led to cognitive deficits, oxidative stress, inflammation, and histopathological changes resembling Alzheimer-like pathological changes in the PFC. However, treatment with AECEL at doses of 400 mg/kg, 600 mg/kg, and 800 mg/kg mitigated these effects, AECEL treatment also ameliorated cognitive and memory dysfunctions. AECEL demonstrated antioxidant and anti-inflammatory properties, as evidenced by decreased malondialdehyde (MDA) levels, increased antioxidant enzyme activity, and reduced inflammatory cytokines. These results highlight the therapeutic potential of AECEL in mitigating Alzheimer’s disease pathology, preserving brain morphology, and improving cognitive function. The use of natural compounds such as AECEL could offer a promising, cost-effective avenue for Alzheimer’s disease treatment, particularly in regions with limited healthcare access. Abbreviations i. AD ii. Alzheimer’s Disease iii. AChE iv. Acetylcholinesterase v. %ALTERN vi. Percentage Alternation vii. AECEL viii. Aqueous Extract of Colocasia esculenta Leaf ix. CE x. Colocasia esculenta xi. DPZ xii. Donepezil xiii. GDH xiv. Glutamate Dehydrogenase xv. GPx xvi. Glutathione Peroxidase xvii. GSH xviii. Glutathione xix. H&E xx. Haematoxylin and Eosin xxi. IL-6 xxii. Interleukin-6 xxiii. IP xxiv. Intraperitoneal xxv. LPS xxvi. Lipopolysaccharide xxvii. MDA xxviii. Malondialdehyde xxix. NDs xxx. Neurodegenerative Diseases xxxi. PFC xxxii. Prefrontal Cortex xxxiii. ROS xxxiv. Reactive Oxygen Species xxxv. S.E.M xxxvi. Standard Error of Mean xxxvii. SOD xxxviii. Superoxide Dismutase xxxix. TNF-α xl. Tumor Necrosis Factor-alpha xli. TWFO xlii. Time Spent With Familiar Object xliii. TWNO xliv. Time Spent With Novel Object Declarations Author Contribution J.A, Siyanbade: Conceptualization, Methodology, Validation, Writing-review&editing and Writing-original draft and Supervision. K.A, Iteire: Methodology,Project administration, Resources, Investigation, Writing-original draft and Supervision. B .J, Leko: Methodology, Project administration and Writing-original draft. S.A, Adelakun: Formal analysis, Investigation and Writing-original draft. K.A, Adebisi: Methodology, Project administration and Writing-original draft. T.S, Oladele: Methodology, Formal analysis and Writing-original draft. O.E, Ogunmiluyi: Methodology, Project administration and Writing-original draft. K.P, Folorunso: Methodology, Project administration and Writing-original draft. H.O, Afolabi: Methodology, Project administration and Writing-original draft. Acknowledgement We appreciate Mr. Adebayo of the Anatomy Department, University of Medical Sciences Ondo, and Mr. Ige of Obafemi Awolowo University, Ife, for all the technical support provided. Data Availability The authors declare that the data supporting the findings of this study are available within the paper and its its supplementary information files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request. References Ayeni, E. A., Aldossary, A. M., Ayejoto, D. A., Gbadegesin, L. A., Alshehri, A. A., Alfassam, H. A., Afewerky, H. K., Almughem, F. A., Bello, S. M., & Tawfik, E. A. (2022). Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. International Journal of Environmental Research and Public Health, 19(19), 12495. https://doi.org/10.3390/ijerph191912495 Thakur, A. K., Kamboj, P., & Goswami, K. (2018). Pathophysiology and management of Alzheimer’s disease: an overview. Journal of Analytical Pharmaceutical Research, 9(2), 226–235. DOI: 10.15406/japIr.2018.07.00230 . Sochocka, M., Zwolińska, K., & Leszek, J. (2017). The Infectious Etiology of Alzheimer’s Disease. Current Neuropharmacology, 15(7), 996–1009. https://doi.org/10.2174/1570159X15666170313122937 Azmand, M. J., & Rajaei, Z. (2021). Effects of crocin on spatial or aversive learning and memory impairments induced by lipopolysaccharide in rat. Avicenna Journal of Phytomedicin e, 11, 79. [PubMed] Jobson DD, Hase Y, Clarkson AN, Kalaria RN. The role of the medial prefrontal cortex in cognition, ageing and dementia. Brain Commun. 2021;3(3):fcab125. doi: 10.1093/braincomms/fcab125 . PMID: 34222873; PMCID: PMC8249104. Preston AR, Eichenbaum H. Interplay of hippocampus and prefrontal cortex in memory. Curr Biol. 2013;23(17):R764-73. doi: 10.1016/j.cub.2013.05.041 . PMID: 24028960; PMCID: PMC3789138. Sudhakar, P., Thenmozhi, V., Srivignesh, S., & Dhanalakshmi, M. (2020). Colocasia esculenta (L.) Schott: Pharmacognostic and pharmacological review. Journal of Pharmacognosy & Phytochemistry, 9(4), 1382–1386. DOI: 10.22271/phyto.2020.v9.i4s.11937 . Keerthy, S. P., & Dr. K Hanumanthachar Joshi. (2019). The pharmacological importance of Colocasia esculenta Linn: A review. Journal of Pharmacognosy and Phytochemistry, 8(6), 1945–1948. Vasant, O. K., Vijay, B. G., Virbhadrappa, S. R., Dilip, N. T., Ramahari, M. V., & Laxamanrao, B. S. (2012). Antihypertensive and Diuretic Effects of the Aqueous Extract of Colocasia esculenta Linn. Leaves in Experimental Paradigms. Iranian Journal of Pharmaceutical Research, 11(2), 621–634. PMID: 24250487; PMCID: PMC3832168. Rebecca Nakaziba, Sharon Bright Amanya, Crispin Duncan Sesaazi, Frederick Byarugaba, Jasper Ogwal-Okeng, Paul E. Alele, "Antimicrobial Bioactivity and GC-MS Analysis of Different Extracts of Corchorus olitorius L Leaves", The Scientific World Journal, vol. 2022, Article ID 3382302, 9 pages, 2022. https://doi.org/10.1155/2022/3382302 Ramirez, Karol; Quesada-Yamasaki, Daniel and Fornaguera-Trias, Jaime.A Protocol to Perform Systemic Lipopolysacharide (LPS) Challenge in Rats. Odovtos [online]. 2019, vol.21, n.1, pp.53–66. ISSN 2215–3411. http://dx.doi.org/10.15517/ijds.v0i0.35510 . Nyonseu Nzebang DC, Ngaha Njila MI, Bend EF, Oundoum Oundoum PC, Koloko BL, Bogning Zangueu C, Belle Ekedi P, Sameza M, Massoma Lembè D. Evaluation of the toxicity of Colocasia esculenta (Aracaceae): Preliminary study of leaves infected by Phytophthora colocasiae on wistar albinos rats. Biomed Pharmacother. 2018;99:1009–1013. doi: 10.1016/j.biopha.2017.12.061. Epub 2018 Feb 20. PMID: 29665641. Varshney R and Kale RF (1990). Effect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes. Int. J. Radiation Biol. 58: 733–743 Adam-vizi V., Seregi M., (1982): Receptor dependent stimulatory effect of noradrenaline on Na+/K + ATPase in rat brain homogenate: Role of lipid peroxidation. Biochem.Pharmacol., 31: 2231–2236 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973;179(4073):588 – 90. doi: 10.1126/science.179.4073.588 . PMID: 4686466. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67–78. doi: 10.1016/0304-4165(79)90289-7 . PMID: 760819. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170–3175. [PubMed] [Google Scholar] Harold J. Strecker, Glutamic dehydrogenase,Archives of Biochemistry and Biophysics, Volume 46, Issue 1,1953,Pages 128–140, ISSN 0003-9861. https://doi.org/10.1016/0003-9861(53)90176-3 . https://www.sciencedirect.com/science/article/pii/0003986153901763 Kraeuter, A. K., Guest, P. C., & Sarnyai, Z. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods in molecular biology (Clifton, N.J.) , 1916, 105–111. https://doi.org/10.1007/978-1-4939-8994-2_10 Lucas Silva Tortorelli, Engelke, D. S., Lunardi, P., Souza, T. M. E., Santos-Junior, J. G., Gonçalves, C. A., et al. (2015). Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression. Behavioural Brain Research, 287, 226–229. https://doi.org/10.1016/j.bbr.2015.03.054 . Meng, H. W., Kim, J. H., Kim, H. Y., Lee, A. Y., & Cho, E. J. (2023). Paeoniflorin Attenuates Lipopolysaccharide-Induced Cognitive Dysfunction by Inhibition of Amyloidogenesis in Mice. International journal of molecular sciences, 24(5), 4838. https://doi.org/10.3390/ijms24054838 Bhattacharyya, A., Chattopadhyay, R., Mitra, S., & Crowe, S. E. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological reviews, 94(2), 329–354. https://doi.org/10.1152/physrev.00040.2012 Kesherwani, R., Kumar, R., Minhas, U., & Rizvi, S. I. (2021). Euglena tuba extract provides protection against lipopolysaccharide-induced inflammatory response and oxidative stress in mice. Biologia, 76(2), 793–798. https://doi.org/10.2478/s11756-020-00623-7 Alagan, A., Jantan, I., Kumolosasi, E., Ogawa, S., Abdullah, M. A., & Azmi, N. (2019). Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats. Frontiers in Pharmacology, 10, Article 632. https://doi.org/10.3389/fphar.2019.00632 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 May, 2024 Reviews received at journal 17 May, 2024 Reviewers agreed at journal 13 May, 2024 Reviews received at journal 12 May, 2024 Reviewers agreed at journal 11 May, 2024 Reviewers invited by journal 10 May, 2024 Editor assigned by journal 30 Apr, 2024 Submission checks completed at journal 30 Apr, 2024 First submitted to journal 22 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4308560","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298884358,"identity":"0861378c-e453-44c5-991b-3b90e9f7cf3f","order_by":0,"name":"Jacob Adewale Siyanbade","email":"data:image/png;base64,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","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":true,"prefix":"","firstName":"Jacob","middleName":"Adewale","lastName":"Siyanbade","suffix":""},{"id":298884362,"identity":"d1e2f90d-2b33-4985-b409-9a72425377bb","order_by":1,"name":"Kingsley Afoke Iteire","email":"","orcid":"","institution":"University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Kingsley","middleName":"Afoke","lastName":"Iteire","suffix":""},{"id":298884366,"identity":"a986eb78-a44d-4a19-9f41-90cace980ec1","order_by":2,"name":"Sunday Aderemi Adelakun","email":"","orcid":"","institution":"Federal University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Sunday","middleName":"Aderemi","lastName":"Adelakun","suffix":""},{"id":298884370,"identity":"30df98b2-f9c3-45d0-aeba-5a99c8beca4a","order_by":3,"name":"Kayode Adedoyin Adebisi","email":"","orcid":"","institution":"University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Kayode","middleName":"Adedoyin","lastName":"Adebisi","suffix":""},{"id":298884373,"identity":"7a1214af-de12-44d4-9efd-be0575d402f0","order_by":4,"name":"Bankole Japhet Leko","email":"","orcid":"","institution":"University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Bankole","middleName":"Japhet","lastName":"Leko","suffix":""},{"id":298884376,"identity":"9a078fdc-333b-4c2b-9ee0-2c7fa017bd26","order_by":5,"name":"Tolulope Samuel Oladele","email":"","orcid":"","institution":"University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Tolulope","middleName":"Samuel","lastName":"Oladele","suffix":""},{"id":298884379,"identity":"1806935d-b9c4-44c2-93fd-05c751d89f38","order_by":6,"name":"Oluwafunmbi Ebenezer Ogunmiluyi","email":"","orcid":"","institution":"Federal University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Oluwafunmbi","middleName":"Ebenezer","lastName":"Ogunmiluyi","suffix":""},{"id":298884383,"identity":"30cd890e-d5cd-4017-98a3-c223c40b0dd6","order_by":7,"name":"Kolade Pelumi Folorunso","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Kolade","middleName":"Pelumi","lastName":"Folorunso","suffix":""},{"id":298884387,"identity":"03298652-b4ce-43b3-87cf-3c31dcf3e3cf","order_by":8,"name":"Hezekiah Omotayo Afolabi","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Hezekiah","middleName":"Omotayo","lastName":"Afolabi","suffix":""}],"badges":[],"createdAt":"2024-04-23 01:25:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4308560/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4308560/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56034355,"identity":"388210c0-a031-4f56-a2a6-07503be356e1","added_by":"auto","created_at":"2024-05-07 18:28:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":888613,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4308560/v1/06eac8ec-a7f7-4801-b162-615a7c2b21c1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ameliorative Effects of Aqueous Extract of Colocasia esculenta Leaf Against Lipopolysaccharide-Induced Prefrontal cortex damage in Mice","fulltext":[{"header":"Highlights","content":"\u003col\u003e\n \u003cli\u003eIntraperitoneal administration of Lipopolysaccharide induced damages to the Prefrontal Cortex of mouse\u003c/li\u003e\n \u003cli\u003eAqueous extract of Colocasia esculenta leaf exhibited antioxidant property\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAqueous extract of Colocasia esculenta leaf ameliorated pathological changes in the Prefrontal cortex.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAqueous extract of Colocasia esculenta leaf has therapeutic potential of mitigating Alzheimer\u0026rsquo;s disease-like pathology and preserving brain morphology.\u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAqueous extract of Colocasia esculenta leaf improved cognitive function.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"1. Background","content":"\u003cp\u003eThe brain is composed of million folds of interconnected cells; the neurons are the most important cells in the brain and any disruptions in these connections lead to brain pathologies, particularly neurodegenerative diseases (NDs) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Alzheimer\u0026rsquo;s disease (AD) is the commonest neurodegenerative disease making up to72% of dementia cases and affects over 50\u0026nbsp;million people worldwide. Its incidence in developing countries has been predicted to increase significantly by 2050 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Many factors contribute to Alzheimer\u0026rsquo;s disease (AD) of which neuroinflammation, oxidative stress, and vascular dysfunctions have been implicated as key factors. Microbial virulence factors, including lipopolysaccharides (LPS), are associated neuroinflammation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. LPSs have been linked to increased Aβ production and tau proteins, whose levels are always elevated in the brain of Alzheimer\u0026rsquo;s disease (AD) patients [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Prefrontal cortex plays spectacular roles in cognition and dementia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and recent studies have significantly increased our understanding of the crucial roles it plays in memory tasks [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMedicinal plants and their extracts have shown diverse biological activities, making them valuable alternative therapies. A systematic approach to evaluating plant products, rooted in phytomedicine, is crucial for the ideal development of new drugs from plants and one of such plants is the \u003cem\u003eColocasia esculent\u003c/em\u003e Linn leaf. \u003cem\u003eColocasia esculenta\u003c/em\u003e (CE), Linn (Family: Araceae), commonly known as \u003cem\u003eTaro\u003c/em\u003e, has been used traditionally for treating different medical conditions [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Some of the implicated phytoconstituents of the leaf include but are not limited to; β-sitosterol, steroids and flavonoids [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, limited information exists on its neuroprotective and neuromodulatory properties [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The current research aimed to assess these aspects, recognizing the sparse data on neuromodulatory effects of AECEL in phytomedicine.\u003c/p\u003e"},{"header":"2.0. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Chemical and reagents\u003c/h2\u003e \u003cp\u003eCommercial kits and reagents for enzyme activity (AChE assay) and protein analysis (ELISA) were purchased from Randox Laboratories Limited (Co Antrim, United Kingdom) and e-bioscience (Inc., San Diego., USA), respectively. Buffers, chemicals, and histological reagents were obtained from Boston Bioproducts, and Sigma-Aldrich Chemical Co ((St. Louis, MO USA). Lipopolysaccharide (5mg of LPS) was gotten from Sigma-Aldrich, USA and donepezil tablets were procured from and Uche Care Pharmacy Ltd, Ondo, Nigeria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Collection and Preparation of Crude AECEL\u003c/h2\u003e \u003cp\u003eFresh \u003cem\u003eColocasia\u003c/em\u003e leaves were harvested from a farm settlement and authenticated with the voucher specimen LHO 840 at the University Department of Botany Herbarium. \u003cem\u003eColocasia esculenta\u003c/em\u003e leaves were washed and subjected to a moderated drying process. The dried leaves were ground into powder form utilizing a grinding machine, (600g) and soaked in distilled water for 48 hours (2 days). Filtration through muslin cloth was conducted to eliminate insoluble particles and impurities. The resultant solution was filtered using Whatman filter paper (No. 1), and the filtrate was concentrated with a rotary evaporator at 20\u0026ndash;28\u0026deg;C. The concentrated crude aqueous extract was stored at a temperature of 4\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u0026deg;C before being reconstituted for administration [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Source of Animals\u003c/h2\u003e \u003cp\u003eForty-two (42) healthy adult (aged: 6-8weeks) Swiss male albino mice with body weights ranging between 18\u0026thinsp;\u0026minus;\u0026thinsp;22g were purchased from the University of Medical Science breeding colony. All the mice were housed in temperature-controlled plastic cages. A 12\u0026thinsp;\u0026minus;\u0026thinsp;hour light\u0026thinsp;\u0026minus;\u0026thinsp;dark cycle was maintained with lights on at 7:00 a.m and food (grower marsh - pellets) and water were provided ad libitum. All the mice were subjected to a 14-day period of acclimatization and all protocols followed the guidelines of the research and ethical committee of the University with index number (UNIMED-AREC/Apv/2023/039).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. LPS-induction\u003c/h2\u003e \u003cp\u003eThe mice were treated with intraperitoneal (IP) injections of 0.5 mg/kg of LPS (E. \u003cem\u003ecoli\u003c/em\u003e O111:B4, Sigma-Aldrich, USA) for seven consecutive days to induce PFC-damage. LPS was prepared using the protocol outlined by Ram\u0026iacute;rez et al. (2019) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Treatment protocol\u003c/h2\u003e \u003cp\u003eTreatment was commenced 48 hours after the induction, for 28 consecutive days following this order of administration; the animals were divided into six groups (Groups A, B, C, D, E, F) Group A (normal control) received distilled water (0.2ml/kg b.w) as a placebo throughout the treatment period. Group B (negative control), the LPS-induced model group, was orally administered distilled water only (0.2ml/kg b.w). Groups C, D, and E, which represent LPS-induced models, received oral AECEL at doses of 400mg/kg/day, 600mg/kg/day, and 800mg/kg/day, respectively. Group F (positive control) consisted of LPS-induced model mice that received oral donepezil (DPZ) at a dose of 2.5mg/kg/day. All the groups were treated once daily under the same housing conditions for a period of 28 days and daily animal weight measurement was ensured using a sensitive weighing scale (Infitek, USA). The LD50 of AECEL has been estimated to be about 4000mg/kg by Nyonseu- Nzebang et al (2018) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Neurobehavioral tests\u003c/h2\u003e \u003cp\u003eNeurobehavioral tests, including Y-Maze, and novel object recognition tests, were carried out to assess lipopolysaccharide-induced neurotoxicity, as well as the ability of AECEL to mitigate neurodegeneration across experimental groups. The assessment was performed before LPS-induction; 24hours post LPS-induction, 14th day of AECEL- treatment and 28th day of AECEL-treatment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7. Sample preparation\u003c/h2\u003e \u003cp\u003eThe animals were sacrificed 24hours post treatment via cervical dislocation. The brains were removed and placed immediately in ice-cold isotonic saline and stored in a freezer. Later the prefrontal cortex was dissected and minced into small pieces, and then homogenized with ten volumes of phosphate buffer (0.1mol/L, PH\u0026thinsp;=\u0026thinsp;7.4) using a WiseTis\u0026reg; (HG-15A) homogenizer. The homogenates were subsequently centrifuged at 13,000 rpm for 10 min and the resulted supernatant was used for the estimation of antioxidant parameters such as reduced Glutathione (GSH), glutathione peroxidise (Gpx), Superoxide dismutase (SOD), Glutamate dehydrogenase (DGH) and Malondialdehyde (MDA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8. Histological analysis\u003c/h2\u003e \u003cp\u003eThe brain tissues were fixed for 48 hours in 10% neutral buffered formalin. Coronal sections of the prefrontal cortex were obtained and the tissue was preserved in 10% neutral buffered formalin and Paraffin wax-embedded blocks for H\u0026amp;E staining were made. Haematoxylin-eosin (H\u0026amp;E) and Bielschowsky staining procedures were performed on the tissue samples.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.9. Determination of Malondialdehyde (MDA) and Glutathione peroxidise (Gpx) Activity assay\u003c/h2\u003e \u003cp\u003eThis was carried out by the Varshney and Kale (1990) procedure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and MDA level was calculated using the method of Adam-Vizi and Seregi (1982) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. And GPx estimation was done according to the method of Rotruck and colleagues (1973) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.10. Determination of reduced Glutathione (GSH) and Superoxide dismutase (SOD) activity\u003c/h2\u003e \u003cp\u003eReduced glutathione assay was done using the protocol of Moron et al. (1979) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. And SOD activity was determined using the method of Misra and Fridovich (1972) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.12. Determination of Glutamate Dehydrogenase (GDH)\u003c/h2\u003e \u003cp\u003eGDH activity assay was done using the method described by Strecker (1953) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e2.13. Neuroinflammatory markers\u003c/h2\u003e \u003cp\u003eFor TNF-α; Elisa kit was used and the assay employs the quantitative sandwich enzyme immunoassay technique. While for the determination of Interleukin-6, the kit uses Sandwich-ELISA principle.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e2.14. Statistical Analysis\u003c/h2\u003e \u003cp\u003eThe results were reported as the mean and standard error of the mean (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M). GraphPad 9 Software (San Diego, USA) was used to analyse the numbers and evaluate the significant differences; comparisons of means between two experimental groups were made using one-way ANOVA with the Newman-Keuls multiple comparison significant difference test and differences were considered significant at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3.0 Results","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Effect of AECEL on the Y-maze test in LPS-induced neuroinflammation\u003c/h2\u003e \u003cp\u003eThis study revealed a significant reduction (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the percentage alternation (%ALTERN) in the LPS-only treated group (Group B) compared to that in Group A. Conversely, groups treated with AECEL (Groups C, D \u0026amp; E) exhibited a significant dose-dependent increase in %ALTERN [Figure\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e], surpassing Group A and the LPS\u0026thinsp;+\u0026thinsp;DPZ (Group F) treatment groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Effect of AECEL on LPS-induced behavioural in the Novel Object Recognition Test\u003c/h2\u003e \u003cp\u003eThe time spent with the familiar object (TWFO) significantly increased, while the time spent with the novel object (TWNO) decreased in the LPS-exposed group compared to group A (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, in the LPS\u0026thinsp;+\u0026thinsp;400 mg AECEL, LPS\u0026thinsp;+\u0026thinsp;600 mg AECEL, and LPS\u0026thinsp;+\u0026thinsp;800 mg AECEL treatment groups, TWFO decreased, and TWNO increased significantly compared to both group A and LPS\u0026thinsp;+\u0026thinsp;DPZ group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e]. Compared with those in the other treatment groups, TWNO in group A and LPS\u0026thinsp;+\u0026thinsp;DPZ group significantly increased. These findings suggest that AECEL treatment, particularly at a 400 mg/kg bw dose, may have a significant impact on the cognitive aspects of mice affected by LPS exposure.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Effect of AECEL treatment on oxidative stress and antioxidant parameters\u003c/h2\u003e \u003cp\u003eThe study revealed a significant increase in brain MDA level in mice exposed to LPS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but posttreatment with AECEL and DPZ resulted in a significant decrease compared to group B (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Interestingly, the LPS\u0026thinsp;+\u0026thinsp;600mg AECEL and LPS\u0026thinsp;+\u0026thinsp;800mg AECEL treatments had nonsignificantly lower values than the LPS\u0026thinsp;+\u0026thinsp;400mg AECEL treatment (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The LPS\u0026thinsp;+\u0026thinsp;400 mg AECEL, LPS\u0026thinsp;+\u0026thinsp;600mg AECEL and LPS\u0026thinsp;+\u0026thinsp;800 mg AECEL treatment groups had significantly greater values than the LPS\u0026thinsp;+\u0026thinsp;DPZ treatment group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e].\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\u003eEffect of AECEL on LPS-induced oxidative stress\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTreatment groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDA\u003c/p\u003e \u003cp\u003e(nmol/g tissue)\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGDH\u003c/p\u003e \u003cp\u003e(nmol/g tissue)\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSOD\u003c/p\u003e \u003cp\u003e(nmol/g tissue)\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGPx\u003c/p\u003e \u003cp\u003e(nmol/g tissue)\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGSH (nmol/gtissue)\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA: Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.90\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e40.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB: LPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.08\u0026thinsp;\u0026plusmn;\u0026thinsp;6.10*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC:LPS\u0026thinsp;+\u0026thinsp;400mgCE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54.46\u0026thinsp;\u0026plusmn;\u0026thinsp;2.57\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e19.19\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD:LPS\u0026thinsp;+\u0026thinsp;600mgCE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e23.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE:LPS\u0026thinsp;+\u0026thinsp;800mgCE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3.72\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e19.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF:LPS\u0026thinsp;+\u0026thinsp;DPZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.32\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e35.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cb\u003eThe data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M, n\u0026thinsp;=\u0026thinsp;10 in each group, *: represents a significant difference from the control, α: represents a significant difference from LPS, β: represents a significant difference from DPZ (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), one-way ANOVA followed by Tukey\u0026rsquo;s post hoc test.\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\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\u003eEffect of AECEL on LPS-induced Neuroinflammation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTreatment groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eInflammatory parameters\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIL-6 (pg/ml)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTNF-α (pg/ml)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA: Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e86.92\u0026thinsp;\u0026plusmn;\u0026thinsp;29.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e49.46\u0026thinsp;\u0026plusmn;\u0026thinsp;7.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB: LPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e265.00\u0026thinsp;\u0026plusmn;\u0026thinsp;14.30*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e130.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.60*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC: LPS\u0026thinsp;+\u0026thinsp;400 mg CE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e163.70\u0026thinsp;\u0026plusmn;\u0026thinsp;9.34\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e92.68\u0026thinsp;\u0026plusmn;\u0026thinsp;7.00\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD: LPS\u0026thinsp;+\u0026thinsp;600 mg CE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e181.20\u0026thinsp;\u0026plusmn;\u0026thinsp;26.24\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e95.86\u0026thinsp;\u0026plusmn;\u0026thinsp;9.17\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE: LPS\u0026thinsp;+\u0026thinsp;800 mg CE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e185.90\u0026thinsp;\u0026plusmn;\u0026thinsp;16.34\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e101.90\u0026thinsp;\u0026plusmn;\u0026thinsp;11.07\u003csup\u003eαβ\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF: LPS\u0026thinsp;+\u0026thinsp;DPZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e86.57\u0026thinsp;\u0026plusmn;\u0026thinsp;6.91\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e64.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cb\u003eThe data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.E.M, n\u0026thinsp;=\u0026thinsp;10 in each group, *: represents a significant difference from the control, α: represents a significant difference from LPS, β: represents a significant difference from DPZ (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), one-way ANOVA followed by Tukey\u0026rsquo;s post hoc test.\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe brain SOD, GPx, and GSH quantities were significantly reduced in the LPS-exposed group than in group A (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but compared with LPS treatment alone, AECEL treatment significantly increased the levels of these antioxidant enzymes levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Notably, the values in the LPS\u0026thinsp;+\u0026thinsp;DPZ treatment group were significantly greater than in LPS\u0026thinsp;+\u0026thinsp;400mg AECEL, LPS\u0026thinsp;+\u0026thinsp;600mg AECEL, and LPS\u0026thinsp;+\u0026thinsp;800mg AECEL groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. These findings suggest that AECEL treatment can reverse LPS-induced oxidative-stress, as indicated by the modulation of MDA, SOD, GPx, and GSH levels.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Effect of AECEL treatment on inflammatory makers\u003c/h2\u003e \u003cp\u003eIn mice exposed to LPS, there was a significant increase (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in IL-6 and TNF-α levels. However, treatment with AECEL resulted in a significant decrease in elevated brain IL-6 and TNF-α levels compared to those in LPS-only group and DPZ-treated mice (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Among the AECEL treatment groups; LPS\u0026thinsp;+\u0026thinsp;600mg AECEL groups showed nonsignificant greater IL-6 and TNF-α levels than the LPS\u0026thinsp;+\u0026thinsp;800mg AECEL group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These findings suggest that AECEL administration effectively reduces inflammatory markers in LPS-only exposed mice in a dose-dependent manner.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Haematoxylin and Eosin staining of the Prefrontal cortex of experimental mice\u003c/h2\u003e \u003cp\u003e \u003cb\u003ePlate 1a,b\u003c/b\u003e, Representative photomicrographs of a coronal section of H and E stained prefrontal morphology of the experimental mice showed the Pia Matter (\u003cb\u003eblack arrow\u003c/b\u003e), the Cortical Layer (\u003cb\u003eCL\u003c/b\u003e), Blood capillaries (\u003cb\u003ebc\u003c/b\u003e) and the White Matter (\u003cb\u003ewm\u003c/b\u003e)\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eControl\u003c/strong\u003e \u003cp\u003eThe prefrontal cortex isfilled with well stained neuronal cells (\u003cb\u003egreen arrows\u003c/b\u003e), with no apparent alterations in histoarchitecture.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eLPS-only: The prefrontal cortex showed signs of degenerative changes in the neurons and numerous cellular degenerations, as indicated by poorly stained nuclei (\u003cb\u003egreen arrows\u003c/b\u003e), cytoplasmic vacuolation (\u003cb\u003ered arrows\u003c/b\u003e), irregular shapes of some neuroglial cells (\u003cb\u003eyellow arrows\u003c/b\u003e), and pyknotic nuclei in some cells (\u003cb\u003eblue arrows).\u003c/b\u003e\u003c/p\u003e \u003cp\u003eLPS\u0026thinsp;+\u0026thinsp;400mg AECEL: The prefrontal cortex showed moderate degeneration of neuronal cells (\u003cb\u003egreen arrows\u003c/b\u003e) with cytoplasmic vacuolation (\u003cb\u003ered arrows\u003c/b\u003e), and the stroma appeared normal.\u003c/p\u003e \u003cp\u003eLPS\u0026thinsp;+\u0026thinsp;600mg AECEL: The prefrontal cortex showed normal laminae and pyramidal neuronal cells (\u003cb\u003egreen arrows\u003c/b\u003e), and the stroma appeared normal.\u003c/p\u003e \u003cp\u003eLPS\u0026thinsp;+\u0026thinsp;800mg AECEL: The prefrontal cortex sections of the animals showed a proper and normal layout of cortical neuronal cells (\u003cb\u003egreen arrows\u003c/b\u003e) from the outermost molecular layer to the innermost multiform layer, with slight dilation (\u003cb\u003ered arrow\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eLPS\u0026thinsp;+\u0026thinsp;DPZ: Several normal neuronal cells (\u003cb\u003egreen arrows\u003c/b\u003e) exhibited cytoplasmic vacuolation (\u003cb\u003ered arrows\u003c/b\u003e), and the stroma appeared normal. These findings imply that the plant extract, particularly at higher doses, may mitigate degenerative changes in the prefrontal cortex, emphasizing its potential therapeutic effects.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Bielschowsky silver staining of the Prefrontal cortex of experimental mice\u003c/h2\u003e \u003cp\u003ePlate 2 Bielschowsky silver staining of the experimental groups after treatment with LPS\u0026thinsp;+\u0026thinsp;400mg AECEL, LPS\u0026thinsp;+\u0026thinsp;600mg AECEL, LPS\u0026thinsp;+\u0026thinsp;800mg AECEL, or LPS\u0026thinsp;+\u0026thinsp;DPZ revealed neuritic plaques (\u003cb\u003ered arrows\u003c/b\u003e) Dissolutions (d), argyrophilic structures (\u003cb\u003eyellow arrows\u003c/b\u003e) and fibrillary amyloid deposits (f) were absent in the control group, but were present to varying degrees in the other groups. These results suggest that the administration of the plant extract and donepezil may influence the presence of these neurodegenerative markers, indicating a potential impact on Alzheimer's disease-like pathology.\u003c/p\u003e \u003c/div\u003e"},{"header":"4.0. Discussion","content":"\u003cp\u003eThe Y-maze test which measures the frequency of alternations, serves as an indicator of cognitive function in rodents [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Prior to LPS-induction (day 0), the mice showed no memory or cognitive deficits. After exposure to LPS, there was a significant decrease in alternation frequency, indicating reduced locomotive ability, consistent with findings on LPS-induced hypolocomotion behavior in mice by Lucas et al., (2015) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Posttreatment with varying doses of AECEL (400, 600, and 800mg/kg bw) alleviated the cognitive deficits induced by LPS. Notably, the alternation frequency was greatest in the LPS\u0026thinsp;+\u0026thinsp;400mg AECEL/kg bw group, suggesting that AECEL has the potential to improve cognitive function in LPS-treated mice, with the 400 mg/kgbw dose showing the most significant improvement.\u003c/p\u003e \u003cp\u003eNovel Object Recognition test assessed memory functions and preferences for new objects in the experimental mice. Following AECEL administration, mice in the LPS-only group showed a preference for the familiar object, spending more time with it than the novel objects when compared with the animals in group A, LPS\u0026thinsp;+\u0026thinsp;DPZ, and AECEL treated groups. Conversely, treatment with AECEL (400, 600, and 800 mg/kgbw) exhibited better preference for the novel object, indicating improved recognition memory compared to that of the LPS-only group. This finding aligns with the findings of Meng et al., (2023) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] who reported that the ability to perceive novel objects was reduced by LPS injection in mice, which improved with Paeoniflorin treatment. Notably, the 400 mg/kgbw AECEL group showed greater preference for the novel object than the groups treated with the other doses (600 and 800 mg/kgbw). The observed preferences suggest that AECEL has the potential to enhance recognition memory in LPS-injected animals, making it a potential treatment for dementia and related diseases.\u003c/p\u003e \u003cp\u003eReactive oxygen species (ROS) can induce reversible or irreversible changes in enzymes and proteins. Glutathione (GSH), a crucial antioxidant, neutralizes cellular H2O2, O2, and lipid hydroperoxides [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In this study, mice treated with LPS alone exhibited increased malondialdehyde (MDA) levels, indicating elevated oxidative stress, and reduced levels of glutamate dehydrogenase (GDH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH), suggesting impaired antioxidant defenses. Treatment with various doses of AECEL (400, 600, and 800 mg/kg bw) significantly decreased the MDA levels and increased the activities of GDH, SOD, GPx, and GSH compared to those in the LPS-only group. This finding suggests that AECEL has potential to mitigate LPS-induced oxidative stress in animals, which is relevant to other disease models. Notably, the 400 mg/kg group showed significant mitigation of oxidative stress compared to the other treatment groups, with the LPS\u0026thinsp;+\u0026thinsp;800 mg/kg group showing a similar effect. This study aligns with the results of Kesherwani et al., 2021 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] who reported that Euglena tuba extract effectively halted the generation of free radical and increase the level of inflammatory cytokines in an LPS-induced mouse model. Compared with those of control animals, LPS-treated animals exhibited elevated inflammatory cytokine production. Treating LPS with AECEL (400\u0026ndash;800 mg/kgbw) significantly reduced cytokine levels, similar to the effects of DPZ in the LPS\u0026thinsp;+\u0026thinsp;DPZ groups. This finding suggests that AECEL has anti-inflammatory properties and is potentially therapeutic for dementia-induced neurological inflammation. Kesherwani et al. (2021) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] reported comparable findings for Euglena tuba extract, indicating its efficacy in countering free radicals and increasing inflammatory cytokines in an LPS-induced mouse model.\u003c/p\u003e \u003cp\u003eFrom the Haematoxylin and Eosin Staining of the prefrontal cortex (Plate 1), the control group's normalcy in histoarchitecture and well-preserved neuronal and non-neuronal cell nuclei serves as a baseline for healthy prefrontal cortex morphology. In contrast, the LPS-only group displayed substantial degenerative changes, including poorly stained nuclei, cytoplasmic vacuolation, irregularly shaped neuroglial cells, and pyknotic nuclei. These pathological alterations are characteristic of Alzheimer's disease and reflect severe neuronal damage. The LPS\u0026thinsp;+\u0026thinsp;400mg AECEL group showed moderate degeneration of neuronal cells and cytoplasmic vacuolation, although the stroma appeared normal. In the LPS\u0026thinsp;+\u0026thinsp;600mg AECEL group, the prefrontal cortex exhibited normal laminae and well-shaped pyramidal neuronal cells, with a healthy stroma. The most significant improvement was observed in the LPS\u0026thinsp;+\u0026thinsp;800mg AECEL group, where a proper and normal layout of cortical neuronal cells was evident, with only slight dilation noted (Plate 1). Standard treatment group, LPS\u0026thinsp;+\u0026thinsp;DPZ, showed some improvement with several normal neuronal cells but still exhibited cytoplasmic vacuolation. The results showed that AECEL has a beneficial effect on preserving the prefrontal cortex morphology and reducing Alzheimer's disease-related changes. Bielschowsky silver staining consolidated the H\u0026amp;E stain observations; neuritic plaques (\u003cb\u003ered arrows\u003c/b\u003e) Dissolutions (d), argyrophilic structures (\u003cb\u003eyellow arrows\u003c/b\u003e) and fibrillary amyloid deposits (f) were absent in the control group, but were present at varying degrees in all the treatment groups. The findings suggest that administration of the plant extract and donepezil may influence the presence of these neurodegenerative markers, indicating a potential impact on Alzheimer's disease-like pathology.\u003c/p\u003e \u003cp\u003eThese results showed that AECEL plays a pivotal role in preserving the health of the prefrontal cortex and ameliorating Alzheimer\u0026rsquo;s disease-related changes although the corresponding histomorphological dose effect has not been established as various structures and signs of improvement were detected across the different doses. These results are similar to the previously reported results of Alagan et al., (2019) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] who reported that the administration of \u003cem\u003ePhyllanthus amarus\u003c/em\u003e extract effectively protected mice from LPS-induced memory impairment.\u003c/p\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Conclusion\u003c/h2\u003e \u003cp\u003eThe administration of lipopolysaccharide (LPS) to mice led to cognitive deficits, oxidative stress, inflammation, and histopathological changes resembling Alzheimer-like pathological changes in the PFC. However, treatment with AECEL at doses of 400 mg/kg, 600 mg/kg, and 800 mg/kg mitigated these effects, AECEL treatment also ameliorated cognitive and memory dysfunctions. AECEL demonstrated antioxidant and anti-inflammatory properties, as evidenced by decreased malondialdehyde (MDA) levels, increased antioxidant enzyme activity, and reduced inflammatory cytokines. These results highlight the therapeutic potential of AECEL in mitigating Alzheimer\u0026rsquo;s disease pathology, preserving brain morphology, and improving cognitive function. The use of natural compounds such as AECEL could offer a promising, cost-effective avenue for Alzheimer\u0026rsquo;s disease treatment, particularly in regions with limited healthcare access.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ei. AD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eii. Alzheimer\u0026rsquo;s Disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eiii. AChE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eiv. Acetylcholinesterase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ev. %ALTERN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evi. Percentage Alternation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003evii. AECEL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eviii. Aqueous Extract of Colocasia esculenta Leaf\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eix. CE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ex. Colocasia esculenta\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exi. DPZ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exii. Donepezil\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exiii. GDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exiv. Glutamate Dehydrogenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exv. GPx\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exvi. Glutathione Peroxidase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exvii. GSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exviii. Glutathione\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exix. H\u0026amp;E\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exx. Haematoxylin and Eosin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxi. IL-6\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxii. Interleukin-6\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxiii. IP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxiv. Intraperitoneal\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxv. LPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxvi. Lipopolysaccharide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxvii. MDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxviii. Malondialdehyde\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxix. NDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxx. Neurodegenerative Diseases\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxxi. PFC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxxii. Prefrontal Cortex\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxxiii. ROS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxxiv. Reactive Oxygen Species\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxxv. S.E.M\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxxvi. Standard Error of Mean\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxxvii. SOD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exxxviii. Superoxide Dismutase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exxxix. TNF-α\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exl. Tumor Necrosis Factor-alpha\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exli. TWFO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exlii. Time Spent With Familiar Object\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003exliii. TWNO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003exliv. Time Spent With Novel Object\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.A, Siyanbade: Conceptualization, Methodology, Validation, Writing-review\u0026amp;editing and Writing-original draft and Supervision. K.A, Iteire: Methodology,Project administration, Resources, Investigation, Writing-original draft and Supervision. B .J, Leko: Methodology, Project administration and Writing-original draft. S.A, Adelakun: Formal analysis, Investigation and Writing-original draft. K.A, Adebisi: Methodology, Project administration and Writing-original draft. T.S, Oladele: Methodology, Formal analysis and Writing-original draft. O.E, Ogunmiluyi: Methodology, Project administration and Writing-original draft. K.P, Folorunso: Methodology, Project administration and Writing-original draft. H.O, Afolabi: Methodology, Project administration and Writing-original draft.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe appreciate Mr. Adebayo of the Anatomy Department, University of Medical Sciences Ondo, and Mr. Ige of Obafemi Awolowo University, Ife, for all the technical support provided.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe authors declare that the data supporting the findings of this study are available within the paper and its its supplementary information files. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAyeni, E. A., Aldossary, A. M., Ayejoto, D. A., Gbadegesin, L. A., Alshehri, A. A., Alfassam, H. A., Afewerky, H. K., Almughem, F. A., Bello, S. M., \u0026amp; Tawfik, E. A. (2022). Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. International Journal of Environmental Research and Public Health, 19(19), 12495. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijerph191912495\u003c/span\u003e\u003cspan address=\"10.3390/ijerph191912495\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThakur, A. K., Kamboj, P., \u0026amp; Goswami, K. (2018). Pathophysiology and management of Alzheimer\u0026rsquo;s disease: an overview. Journal of Analytical Pharmaceutical Research, 9(2), 226\u0026ndash;235. DOI: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.15406/japIr.2018.07.00230\u003c/span\u003e\u003cspan address=\"10.15406/japIr.2018.07.00230\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSochocka, M., Zwolińska, K., \u0026amp; Leszek, J. (2017). The Infectious Etiology of Alzheimer\u0026rsquo;s Disease. Current Neuropharmacology, 15(7), 996\u0026ndash;1009. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2174/1570159X15666170313122937\u003c/span\u003e\u003cspan address=\"10.2174/1570159X15666170313122937\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzmand, M. J., \u0026amp; Rajaei, Z. (2021). Effects of crocin on spatial or aversive learning and memory impairments induced by lipopolysaccharide in rat. \u003cem\u003eAvicenna Journal of Phytomedicin\u003c/em\u003ee, 11, 79. [PubMed]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJobson DD, Hase Y, Clarkson AN, Kalaria RN. The role of the medial prefrontal cortex in cognition, ageing and dementia. Brain Commun. 2021;3(3):fcab125. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/braincomms/fcab125\u003c/span\u003e\u003cspan address=\"10.1093/braincomms/fcab125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 34222873; PMCID: PMC8249104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePreston AR, Eichenbaum H. Interplay of hippocampus and prefrontal cortex in memory. Curr Biol. 2013;23(17):R764-73. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.cub.2013.05.041\u003c/span\u003e\u003cspan address=\"10.1016/j.cub.2013.05.041\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 24028960; PMCID: PMC3789138.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSudhakar, P., Thenmozhi, V., Srivignesh, S., \u0026amp; Dhanalakshmi, M. (2020). \u003cem\u003eColocasia esculenta\u003c/em\u003e (L.) Schott: Pharmacognostic and pharmacological review. Journal of Pharmacognosy \u0026amp; Phytochemistry, 9(4), 1382\u0026ndash;1386. DOI:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.22271/phyto.2020.v9.i4s.11937\u003c/span\u003e\u003cspan address=\"10.22271/phyto.2020.v9.i4s.11937\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeerthy, S. P., \u0026amp; Dr. K Hanumanthachar Joshi. (2019). The pharmacological importance of \u003cem\u003eColocasia esculenta\u003c/em\u003e Linn: A review. Journal of Pharmacognosy and Phytochemistry, 8(6), 1945\u0026ndash;1948.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVasant, O. K., Vijay, B. G., Virbhadrappa, S. R., Dilip, N. T., Ramahari, M. V., \u0026amp; Laxamanrao, B. S. (2012). Antihypertensive and Diuretic Effects of the Aqueous Extract of \u003cem\u003eColocasia esculenta\u003c/em\u003e Linn. Leaves in Experimental Paradigms. Iranian Journal of Pharmaceutical Research, 11(2), 621\u0026ndash;634. PMID: 24250487; PMCID: PMC3832168.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRebecca Nakaziba, Sharon Bright Amanya, Crispin Duncan Sesaazi, Frederick Byarugaba, Jasper Ogwal-Okeng, Paul E. Alele, \"Antimicrobial Bioactivity and GC-MS Analysis of Different Extracts of Corchorus olitorius L Leaves\", The Scientific World Journal, vol. 2022, Article ID 3382302, 9 pages, 2022. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1155/2022/3382302\u003c/span\u003e\u003cspan address=\"10.1155/2022/3382302\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamirez, Karol; Quesada-Yamasaki, Daniel and Fornaguera-Trias, Jaime.A Protocol to Perform Systemic Lipopolysacharide (LPS) Challenge in Rats. Odovtos [online]. 2019, vol.21, n.1, pp.53\u0026ndash;66. ISSN 2215\u0026ndash;3411. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.15517/ijds.v0i0.35510\u003c/span\u003e\u003cspan address=\"10.15517/ijds.v0i0.35510\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNyonseu Nzebang DC, Ngaha Njila MI, Bend EF, Oundoum Oundoum PC, Koloko BL, Bogning Zangueu C, Belle Ekedi P, Sameza M, Massoma Lemb\u0026egrave; D. Evaluation of the toxicity of Colocasia esculenta (Aracaceae): Preliminary study of leaves infected by Phytophthora colocasiae on wistar albinos rats. Biomed Pharmacother. 2018;99:1009\u0026ndash;1013. doi: 10.1016/j.biopha.2017.12.061. Epub 2018 Feb 20. PMID: 29665641.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVarshney R and Kale RF (1990). Effect of calmodulin antagonists on radiation induced lipid peroxidation in microsomes. Int. J. Radiation Biol. 58: 733\u0026ndash;743\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdam-vizi V., Seregi M., (1982): Receptor dependent stimulatory effect of noradrenaline on Na+/K\u0026thinsp;+\u0026thinsp;ATPase in rat brain homogenate: Role of lipid peroxidation. Biochem.Pharmacol., 31: 2231\u0026ndash;2236\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973;179(4073):588\u0026thinsp;\u0026ndash;\u0026thinsp;90. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1126/science.179.4073.588\u003c/span\u003e\u003cspan address=\"10.1126/science.179.4073.588\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 4686466.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67\u0026ndash;78. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0304-4165(79)90289-7\u003c/span\u003e\u003cspan address=\"10.1016/0304-4165(79)90289-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 760819.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170\u0026ndash;3175. [PubMed] [Google Scholar]\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarold J. Strecker, Glutamic dehydrogenase,Archives of Biochemistry and Biophysics, Volume 46, Issue 1,1953,Pages 128\u0026ndash;140, ISSN 0003-9861.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0003-9861(53)90176-3\u003c/span\u003e\u003cspan address=\"10.1016/0003-9861(53)90176-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.sciencedirect.com/science/article/pii/0003986153901763\u003c/span\u003e\u003cspan address=\"https://www.sciencedirect.com/science/article/pii/0003986153901763\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKraeuter, A. K., Guest, P. C., \u0026amp; Sarnyai, Z. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. \u003cem\u003eMethods in molecular biology (Clifton, N.J.)\u003c/em\u003e, 1916, 105\u0026ndash;111. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/978-1-4939-8994-2_10\u003c/span\u003e\u003cspan address=\"10.1007/978-1-4939-8994-2_10\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLucas Silva Tortorelli, Engelke, D. S., Lunardi, P., Souza, T. M. E., Santos-Junior, J. G., Gon\u0026ccedil;alves, C. A., et al. (2015). Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression. Behavioural Brain Research, 287, 226\u0026ndash;229. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bbr.2015.03.054\u003c/span\u003e\u003cspan address=\"10.1016/j.bbr.2015.03.054\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng, H. W., Kim, J. H., Kim, H. Y., Lee, A. Y., \u0026amp; Cho, E. J. (2023). Paeoniflorin Attenuates Lipopolysaccharide-Induced Cognitive Dysfunction by Inhibition of Amyloidogenesis in Mice. International journal of molecular sciences, 24(5), 4838. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms24054838\u003c/span\u003e\u003cspan address=\"10.3390/ijms24054838\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhattacharyya, A., Chattopadhyay, R., Mitra, S., \u0026amp; Crowe, S. E. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiological reviews, 94(2), 329\u0026ndash;354. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1152/physrev.00040.2012\u003c/span\u003e\u003cspan address=\"10.1152/physrev.00040.2012\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKesherwani, R., Kumar, R., Minhas, U., \u0026amp; Rizvi, S. I. (2021). Euglena tuba extract provides protection against lipopolysaccharide-induced inflammatory response and oxidative stress in mice. Biologia, 76(2), 793\u0026ndash;798. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2478/s11756-020-00623-7\u003c/span\u003e\u003cspan address=\"10.2478/s11756-020-00623-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlagan, A., Jantan, I., Kumolosasi, E., Ogawa, S., Abdullah, M. A., \u0026amp; Azmi, N. (2019). Protective effects of Phyllanthus amarus against lipopolysaccharide-induced neuroinflammation and cognitive impairment in rats. Frontiers in Pharmacology, 10, Article 632. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fphar.2019.00632\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2019.00632\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-applied-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Applied Sciences](https://link.springer.com/journal/42452)","snPcode":"42452","submissionUrl":"https://submission.springernature.com/new-submission/42452/3","title":"Discover Applied Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Colocasia esculenta, Donepezil, Lipopolysaccharide, Prefrontal-cortex","lastPublishedDoi":"10.21203/rs.3.rs-4308560/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4308560/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe prefrontal-cortex (PFC) occupies about one-third of the total area of the cerebral cortex and it plays crucial role in Cognition and memory. This study evaluated the ameliorative effects of aqueous extract of \u003cem\u003eColocasia esculenta\u003c/em\u003e leaf (AECEL) on lipopolysaccharide-induced Prefrontal-cortex damage.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e42 Swiss male albino mice with weights ranging between 18\u0026thinsp;\u0026minus;\u0026thinsp;22g were randomized into six-groups. Group-A consisted of healthy-mice and LPS-induction in groups (B-F) was done by intraperitoneal injections of 0.5mg/kg of lipopolysaccharide (LPS) for seven days. Group-B received distilled-water; Group C- E was treated with AECEL at 400 mg/kg, 600 mg/kg and 800 mg/kg respectively, while Group F received 2.5 mg/kg of donepezil (DPZ) via oral-gavage for 28days.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSignificant increase in the brain oxidative-stress parameters was seen in the LPS-exposed groups compared to the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, compared with those in the LPS-only group, the levels of oxidative-stress parameters as well as Tumour-necrosis factor-α and interleukin-6 in the brain of AECEL-and DPZ-treated groups were significantly lower (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the Y-maze test: the percentage-alternation (%ALTERN) significantly decreased (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the LPS-only group compared to that in the control-group, but there was a significant increase in the %ALTERN in the AECEL-treated groups compared to that in the LPS-only and LPS\u0026thinsp;+\u0026thinsp;DPZ treatment groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Bielschowsky staining revealed that the LPS-only group exhibited senile-plaques and neurofibrillary-tangles.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLPS caused damage to the PFC; AECEL significantly improved cognitive function, memory, and anxiety-like behaviours.\u003c/p\u003e","manuscriptTitle":"Ameliorative Effects of Aqueous Extract of Colocasia esculenta Leaf Against Lipopolysaccharide-Induced Prefrontal cortex damage in Mice","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-07 18:28:16","doi":"10.21203/rs.3.rs-4308560/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-21T07:01:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-17T11:03:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293994780819230417024266444202940073400","date":"2024-05-13T05:53:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-12T11:02:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196466855742307658653490074461653491292","date":"2024-05-11T07:30:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-10T16:31:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-30T12:58:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-30T12:52:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Applied Sciences","date":"2024-04-23T01:13:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-applied-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Applied Sciences](https://link.springer.com/journal/42452)","snPcode":"42452","submissionUrl":"https://submission.springernature.com/new-submission/42452/3","title":"Discover Applied Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f5d65de7-910b-4ace-869a-a1534a34dd15","owner":[],"postedDate":"May 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-07-24T13:31:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-07 18:28:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4308560","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4308560","identity":"rs-4308560","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}