Walnut peptide and ginseng Rg1 co-treatment prevents the loss of neurons and cognitive decline in mouse model with memory impairment

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.