Objective(s): Annona muricata” (soursop) is a medicinal plant with diverse ornamental, consumptive, and pharmacological importance. This study was designed for its anti-amnesic potential in mice. Materials and Methods: The crude extract was fractionated with n-hexane, ethyl acetate, and aqueous methanol. The crude and fractions were tested in vitro for the anti-oxidant radical scavenging activity (DPPH), total flavonoid and phenolic content, and their acetylcholinesterase inhibitory activity. Thinlayer chromatography was used to determine the phytochemicals contained in the fractions and their purity. Neurobehavioral models like the Open Field Test, Novel Object Recognition Test, Y-Maze, and Morris Water Maze were used to evaluate the action of AMME (Annona muricata methanol extract) and AMAMF (Annona muricata aqueous methanol fraction). Results: The AMME and AMAMF significantly reduced the serum levels of myeloperoxidase and arginine (P<0.05). They also modulate the hippocampal and prefrontal acetylcholinesterase and glutamic acid decarboxylase activities (P<0.05). The 25 mg/kg AMAMF significantly affected short-term memory (P<0.05). The AMAMF and AMME significantly enhanced the prefrontal and hippocampal tissue levels of glutathione and superoxide dismutase. During the in vitro AchE assay on all fractions, the AMME and AMAMF consistently showed the greatest percentage of inhibitory activity. They inhibited 50% of the AchE enzymes with the lowest concentration. Conclusion: The study showed the neuroprotective effects of AMME and AMAMF in memory impairment models. The extracts showed potent AChE inhibition and positive effects on memory and anti-oxidant enzyme levels.

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