Bushen Yinao pill improves cognitive function in Alzheimer's disease rats by regulating PI3K/Akt pathway and intestinal microbiota.

Abstract

Bushen Yinao Pill (BSYN), a traditional Chinese medicine (TCM), is commonly employed to treat forgetfulness and kidney deficiency. The objective of this research was to explore the curative effect of BSYN in Alzheimer's disease (AD) rats and to delve into its underlying mechanism of action. The chemical composition of BSYN was examined by means of UPLC-Q-TOF-MS/MS. The rat model of AD was established using Aβ, alumina, and D-galactose. Through the Morris Water Maze test (MWM), cognitive function was evaluated. To observe the pathological changes in the hippocampus, Hematoxylin and eosin (HE) staining was applied. The oxidative stress level and cholinergic nerve factors were measured using the enzyme-linked immunosorbent assay (ELISA). Moreover, Western blot was utilized for detecting proteins related to the PI3K/Akt pathway. Gut microbiota composition was analyzed using 16S rDNA sequencing. In total, 203 compounds of BSYN were identified. BSYN significantly improved cognitive performance, reduced hippocampal histopathological damage, and restored markers of oxidative stress. Additionally, BSYN modulated the PI3K/Akt pathway by enhancing p-PI3K and p-Akt expression and downregulating GSK-3β. Gut microbiota analysis revealed that BSYN restored microbial diversity and composition, increasing beneficial bacteria such as Lactobacillus while reducing pro-inflammatory genera like Lachnospiraceae NK4A136. In conclusion, the study revealed that BSYN can improve AD-like pathology in rats by modulating several aspects. These findings provide a mechanistic basis for BSYN's therapeutic potential in AD and support its further development as a novel intervention for neurodegenerative diseases.