Bavachin Attenuates Cognitive Impairment in Scopolamine‐Induced Amnesia: Behavioral, Biochemical and Molecular Insights

ABSTRACT Cholinergic dysfunction is a key feature of cognitive impairment, and currently available acetylcholinesterase (AChE) inhibitors provide limited symptomatic benefit and are often associated with adverse effects. This study evaluated the cognitive‐protective effects of bavachin (BVC), a prenylated flavonoid from Psoralea corylifolia, and its interaction with Donepezil (DNP) in a scopolamine (SCP)‐induced amnesia model. Male Swiss albino mice were pretreated with BVC (10–40 mg/kg), DNP (2.5 mg/kg), or their combination for 7 days prior to SCP challenge, followed by assessment using multiple behavioral paradigms, including novel object recognition, elevated plus maze, passive avoidance, Y‐maze, and Morris water maze. BVC attenuated SCP‐induced memory deficits in a dose‐dependent manner, with the 40 mg/kg dose producing performance statistically comparable to, though not formally demonstrated to be equivalent to, the normal control across tests. Bliss independence analysis of behavioral endpoints indicated predominantly additive interactions, with occasional greater‐than‐additive trends. Biochemical evaluation demonstrated that BVC inhibits AChE in vitro (IC 50 = 27.7 µM) and attenuates SCP‐induced elevations of AChE activity ex vivo in the frontal cortex and hippocampus. Combination treatment showed a greater‐than‐additive interaction in the frontal cortex (ΔBliss = 0.054) and an approximately additive effect in the hippocampus (ΔBliss = 0.013). Molecular docking and molecular dynamics simulations further suggested stable binding of BVC within the active sites of AChE and butyrylcholinesterase (BChE). Collectively, these findings indicate that BVC attenuates cognitive deficits, at least in part, through cholinesterase inhibition, and exhibits additive effects with DNP, supporting its potential as an adjunctive candidate for cognitive disorders.