Investigation of the intervention mechanism of total flavonoids of Polygonum divaricatum L. on MPTP-induced Parkinson's disease mice based on the interaction between metabolomics and gut microbial diversity.

Parkinson's disease (PD) is a complex neurodegenerative disorder, and much evidence has shown that the diversity of gut flora is related to its pathogenesis. Therefore, the aim of this study was to investigate the mechanism of action of total flavonoids of Polygonum divaricatum L. (TFP) on PD treatment from the perspective of gut microbiology and metabolomics. In this study, the MPTP-induced mouse model was used to evaluate the therapeutic potential of TFP in PD. The main components of TFP were quantified by the LC-MS/MS technique. Following TFP treatment, we evaluated motor function in PD mice through behavioral tests, and then conducted H&E staining, IHC, ELISA, Western blotting, 16S rDNA sequencing, and metabolomics analyses to elucidate the underlying mechanisms of TFP's therapeutic effects. As a result, TFP significantly alleviated pathological symptoms in PD mice. The 16S rDNA gene sequencing results showed that TFP elevated the relative abundance of the beneficial genera Lactobacillus and Bacteroides and decreased the relative abundance of the pathogenic genera Desulfovibrio and Escherichia-Shigella. Metabolomics analysis indicated that TFP modulates key pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and primary bile acid biosynthesis, via differential metabolites such as tyrosine, 7-ketolithocholic acid, and ursodeoxycholic acid. Correlation analysis further revealed significant associations between these altered gut microbes and specific metabolites. In conclusion, our findings demonstrate that TFP alleviates the typical pathological changes and intestinal dysfunction in PD mice, and its mechanism is potentially mediated through the remodeling of gut microbiota and associated metabolic functions.