Acanthopanax senticosus Harms improves Parkinson's disease by regulating gut microbial structure and metabolic disorders

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease, with an increasing prevalence as the population ages, posing a serious threat to human health, but the pathogenesis remains uncertain. Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) (aqueous ethanol extract), a Chinese herbal medicine, provides obvious and noticeable therapeutic effects on PD. To further investigate the ASH's mechanism of action in treating PD, the structural and functional gut microbiota, as well as intestinal metabolite before and after ASH intervention in the PD mice model, were examined utilizing metagenomics and fecal metabolomics analysis. α-syn transgenic mice were randomly divided into a model and ASH groups, with C57BL/6 mice as a control. The ASH group was gavaged with ASH (45.5 mg/kg/d for 20d). The time of pole climbing and autonomous activity were used to assess motor ability. The gut microbiota's structure, composition, and function were evaluated using Illumina sequencing. Fecal metabolites were identified using UHPLC-MS/MS to construct intestinal metabolites. The findings of this experiment demonstrate that ASH may reduce the climbing time of PD model mice while increasing the number of autonomous movements. The results of metagenomics analysis revealed that ASH could up-regulated Firmicutes and down-regulated Actinobacteria at the phylum level, while Clostridium was up-regulated and Akkermansia was down-regulated at the genus level; it could also recall 49 species from the phylum Firmicutes, Actinobacteria, and Tenericutes. Simultaneously, metabolomics analysis revealed that alpha-Linolenic acid metabolism might be a key metabolic pathway for ASH to impact in PD. Furthermore, metagenomics function analysis and metabolic pathway enrichment analysis revealed that ASH might influence unsaturated fatty acid synthesis and purine metabolism pathways. These metabolic pathways are connected to ALA, Palmitic acid, Adenine, and 16 species of Firmicutes, Actinobacteria, and Tenericutes. Finally, these results indicate that ASH may alleviate the movement disorder of the PD model, which may be connected to the regulation of gut microbiota structure and function as well as the modulation of metabolic disorders by ASH.