Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimer's disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat. The effects of EEPEr and EEPEu fruits (i.e., 100 and 200 mg/kg b.w.) were examined in Swiss albino male rats for 12 days and its effect on cognitive functions, brain antioxidant enzymes, and AChE activity determined. Learning and memory enhancing activity of EEPE fruit was examined by using passive avoidance test and rewarded alternation test. Antioxidant potentiality was evaluated by measuring the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase, reduced glutathione (GSH), glutathione-S-transferase, and the contents of thiobarbituric acid reactive substances (TBARS) in entire brain tissue homogenates. AChE activity was determined using colorimetric method. Administration of the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.01) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.05, p < 0.001) increased step-through latency in rats on 6th, 11th, and 12th day with respect to the control group. For aforementioned doses, the percentage of memory retention (MR) was considerably (p < 0.05, p < 0.01) increased in rats on 10th, 11th, and 12th days with respect to the control group. The extract, particularly highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit markedly (p < 0.05) and lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit significantly (p < 0.01) increased the correct responses in rats on 6th, and 12th day related to the control group. In case of this test, the percentage of MR was significantly (p < 0.05, p < 0.01) increased in rats treated with aforementioned doses on 12th day with respect to the control group. The highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit suggestively (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit suggestively (p < 0.05, p < 0.01, p < 0.001) increased the levels of SOD, CAT, GSH, GSH-Px and expressively (p < 0.01) decreased the TBARS level compared to the control group. Treatment with the highest dose (i.e., 200 mg/kg b.w.) of EEPEr fruit significantly (p < 0.05) and both lowest and highest doses (i.e., 100 and 200 mg/kg b.w.) of EEPEu fruit markedly (p < 0.01, p < 0.001) decreased the level of AChE activity compared to that of the control group. The present study shows that EEPE fruit possesses an excellent source for natural cognitive enhancer which could be developed in the treatment of AD and other neurodegenerative diseases.

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