Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer’s disease (AD). Our quantitative preliminary study revealed the presence of several neuroprotective flavonoids in Cajanus cajan seed extract. Hence, this study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Adult mice were first pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days. Scopolamine an anti-muscarinic agent (1mg/kg) was given an hour after CC pretreatment from days 3 to 16. The mice were subjected to behavioural tests (open field test (OFT), Y-maze test (YMT) or Morris water maze task (MWM). Animals were euthanized on day 16 and biochemical analysis was carried on the brain tissue to assay for biomarkers of oxidative stress and cholinergic system. Molecular docking analysis was also done to investigate the possible mechanism(s) through which CC exerts its anti-amnesic action. The results showed that the pre-administration of CC ameliorated working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. CC improved cholinergic function via attenuation of scopolamine-induced increase in acetylcholinesterase activity in the hippocampus. Furthermore, CC attenuated scopolamine-induced oxidative stress and increased nitrite generation in the hippocampus evidenced in significant increase in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) levels. Phytochemicals obtained from CC displayed significant interaction at the M1 muscarinic acetylcholine receptor, alpha-7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets which suggests the involvement of these target proteins in the activity of CC. Findings obtained from this study showed that CC improved working memory and learning through enhancement of cholinergic systems and reduction in amyloidogenesis.
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