The modulatory role of prime identified compounds in Geophila repens in mitigating scopolamine-induced neurotoxicity in experimental rats of Alzheimer's disease via attenuation of cholinesterase, β-secretase, MAPt levels and inhibition of oxidative stress imparts inflammation
| Autor: | Purusottam Banjare, Satish Kanhar, Atish Kumar Sahoo, Partha Pratim Roy, Sandeep Kumar Swain, Umesh Chandra Dash, Jagneshwar Dandapat |
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| Rok vydání: | 2022 |
| Předmět: |
Mydriatics
Antioxidant Aché medicine.medical_treatment Scopolamine tau Proteins Pharmacology medicine.disease_cause Neuroprotection Neurochemical Alzheimer Disease Memory Drug Discovery medicine Animals Neuroinflammation Cholinesterase Inflammation Memory Disorders biology Chemistry Neurotoxicity medicine.disease language.human_language Rats Oxidative Stress Neuroprotective Agents Gene Expression Regulation language biology.protein Cholinesterase Inhibitors Amyloid Precursor Protein Secretases Agaricales Oxidative stress |
| Zdroj: | Journal of Ethnopharmacology. 282:114637 |
| ISSN: | 0378-8741 |
| Popis: | Ethnopharmacological relevance Geophila repens (L.) I.M. Johnst (Rubiaceae) is a small perennial creeper native to India, China, and other countries in Southeast Asia. The hot decoction of leaves is used orally for memory enhancing by the local folk of Andhra Pradesh, India. The ethnomedicinal claim of G. repens as memory enhancer was initially studied by the authors. Results demonstrated the important antioxidant and anticholinesterase activities of isolated molecule Pentylcurcumene and bioactive hydroalcohol extract of leaves of G. repens (GRHA). Aim of the study Based on the previous findings, additional research is needed to examine the efficacy of GRHA for memory enhancing properties. We therefore investigated the modulatory role of prime identified compounds in GRHA in mitigating scopolamine-induced neurotoxicity in experimental rats of Alzheimer's disease (AD) via attenuation of cholinesterase, β-secretase, MAPt levels and inhibition of oxidative stress imparts inflammation. Methods Scopolamine (3 mg/kg) induced experimental rats of AD were treated with GRHA (300, 400 mg/kg) for 14 days. During the experimental period, elevated T-maze and locomotion-activity were performed to assess learning and memory efficacy of GRHA. At the end of the experiment, biochemical, neurochemical, neuroinflammation and histopathological observation of brain cortex were examined. GC-MS/MS analysis reported 31 compounds, among them 8 bioactive compounds possess antioxidant, neuroinflammation, neuroprotective activities, and were considered for docking analysis towards cholinesterase, β-secretase activities in AD. Results GRHA 400 significantly improved learning and memory impairment with the improvement of oxidative stress (MDA, SOD, GSH, CAT), DNA damage (8-OHdG), neurochemical (AChE, BuChE, BACE1, BACE2, MAPt), neuroinflammation (IL-6, TNF-α) markers in neurotoxic rats. Docking studies of 8 compounds demonstrated negative binding energies for cholinesterase and β-secretase indicating high affinity for target enzymes in AD. Test results were corroborated by the improvement of cellular tissue architecture of brain cortex in AD rats. Conclusion Synergistic action of genistin, quercetin-3-D-galactoside, 9,12,15-octadecatrienoic-acid methyl-ester, phytol, retinal, stigmasterol, n-hexadecanoic acid, β-sitosterol in GRHA restores memory-deficits via attenuation of cholinesterase, β-secretase, MAPt level and inhibition of oxidative-stress imparts inflammation in AD. |
| Databáze: | OpenAIRE |
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