Ginsenoside Rk3 Alleviates Neuroinflammation and Gastrointestinal Dysfunction in Parkinson's Disease via Modulation...

Accumulating evidence links gut microbiota dysbiosis and metabolic disorders to the pathogenesis of Parkinson's disease (PD). Ginsenoside Rk3 (Rk3), a rare ginseng saponin, possesses anti-inflammatory and microbiota-modulating properties. However, its role in the regulation of the gut-brain axis remains unclear. In this study, the key gut microbial species and microbial metabolites associated with the PD-protective effects of Rk3 was explored using rotenone-induced PD mouse model through behavioral experiments, multiomics analysis and targeted bacteria/metabolites supplementation. Rk3 could restore the intestinal microbial homeostasis by enriching Lactobacillus murinus and Clostridium, and delay PD progression by lightening neuroinflammation in a gut microbiota-dependent manner. Crucially, Rk3 significantly increased levels of microbial metabolite butyrate, which could protect dopaminergic neurons and mitigate neuroinflammation by inhibiting histone deacetylase (HDAC) activity and activating the JAK/STAT3 signaling pathway. Overall, Rk3 delays PD progression via intestinal microbial homeostasis remodeling, highlighting its therapeutic potential for neurodegenerative disorders mediated by the gut-brain axis.