Background: Isofraxidin is a coumarin compound mainly isolated from several traditional and functional edible plants bene cial for neurodegenerative diseases, including Sarcandra glabra and Apium graveolens, and Siberian Ginseng.Objective: This study aimed to assess effects of isofraxidin against memory impairments and cognition de cits in a scopolamine-induced mouse model.Materials & methods: Animals were randomly divided into 6 groups, control, vehicle, donepezil (10 mg/kg, p.o.), and isofraxidin (3, 10, and 30 mg/kg, p.o.). Isofraxidin or donepezil was administered for 44 days, once per day. The scopolamine insults (1 mg/kg, i.p.) was given from the 21 st day, once per day. Morris water maze test and Y-maze test were used for the behavioral test. After that, brain samples were collected for analysis.Results: Firstly, isofraxidin signi cantly improved scopolamine-induced behavioral impairments and cognition de cits in Morris water maze and Y-maze test. Then, isofraxidin facilitated cholinergic activity via inhibiting acetylcholinesterase (AChE) activity. Besides, isofraxidin decreased lipid peroxidation level but enhanced levels of glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, isofraxidin suppressed the expression of in ammatory mediators and cytokines. Further investigations showed that isofraxidin up-regulated expression of brain-derived neurotrophic factor (BDNF), and promoted phosphorylation of tropomyosin-related kinase B (TrkB), cyclic AMP-response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK).Discussion & Conclusion: These results suggested that isofraxidin ameliorated scopolamine-induced cognitive and memory impairments, possibly through regulating AChE activity, suppressing oxidative stress and in ammatory response, and modulating BDNF-CREB-ERK pathways.