P1‐207: NEUROPROTECTIVE EFFECT OF POLYPHENOLIC RICH EXTRACT OF AEGLE MARMELOS IN ALZHEIMER'S DISEASE LIKE PATHOLOGY VIA MAINTAINING OXIDATIVE BALANCE AND ACETYLCHOLINE LEVEL

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative mental disorder amongst aging people which is associated with impairment in cognitive functions. Free radicals as well as cholinergic deficit neuron within nucleus basalis magnocellularis further attributed with aggregation of β amyloid contributes as an essential hallmark in AD. Hydroethanolic extract of Aegle marmelos (HEAM) fruit pulp was quantitatively estimated for individual polyphenolic compounds by HPLC-DAD analysis which exhibited the presence of rich amount of chlorogenic acid, protocatechuic acid and caffeic acid. In present study we estimated the neuropharmacological potential of HEAM on hippocampal memory deficit induced by scopolamine injection in rodents. Swiss albino mice were orally preadministered with HEAM (200, 400, and 600 mg/kg) and Donepezil (1mg/kg) for 21days. To assess cognitive function, Elevated plus maze and Hebbs William maze task were performed for consecutively 2 days. Homogenized brain hippocampus was used for enzymatic antioxidant level, AChE inhibitory activity determination as well as gene expression determination. Scopolamine injection elevated the TL (transfer latency) and TRC (Time taken to reach the reward chamber), which were significantly reversed by pretreatment with HEAM in a dose dependent manner. In addition, acetylcholinesterase activity, enzymatic and nonenzymatic oxidant-antioxidant balance level, neurogenesis and their concerning pathways were markedly distorted by scopolamine in hippocampal region, whereas those impairments were significantly ameliorated with HEAM pretreatment. Brain derived neurotrophic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) gene expression were accelerated by HEAM preadminstration. Molecular docking studies exhibited the highest binding affinity of chlorogenic acid towards acetylcholinesterase receptor with docking score -8.13. The current findings advocates that HEAM could be a strong neuroprotective agent against cognitive deficit associated with AD and its possible underlying mechanism might be improving brain cholinergic status through CREB-BDNF pathway as well as oxidative balance.