摘要In study,we investigated the effect of treatment with combination of walnut peptides with molecular weight<3 kDa and ginsenoside Rg1(<3 kDa+Rg1)on scopolamine-induced cognitive impairment in mice and the mechanism of brain-derived neurotrophic factor(BDNF)/tyrosine kinase B(TrKB)/cAMP response element-binding protein(CREB)signaling pathway in PC12 cells.In behavioral experiments,<3 kDa+Rg1 treatment improved the memorizing ability of mice.Treatment with<3 kDa+Rg1 significantly regulated the function of neurotransmitters and effectively improved the morphology of the neurons determined by hematoxylin and eosin(H&E),Nissl,and Golgi staining.Additionally,immunohistochemistry showed that the<3 kDa+Rg1 treatment significantly decreased acetylcholinesterase(AChE)activity and increased choline acetyl transferase(ChAT)content in the hippocampus.The treatment upregulated vesicular acetylcholine transporter(VAChT),activated the BDNF/TrKB/CREB signaling pathway,improved the remodeling of dendritic spines,and enhanced cholinergic functions.In the scopolamine-induced PC12 cells,combination treatment increased thioredoxin-1(Trx-1)expression after administering TrKB and activated signaling pathway.The results showed combination of<3 kDa+Rg1 activated the BDNF/TrKB/CREB signaling pathway by regulating function of neurotransmitters and enhanced cholinergic function to decrease cognitive impairment.