Ginsenosides modulate immunity via TLR4/MyD88/NF-κB pathway and gut microbiota

Background: Ginsenosides, the primary active compounds in Panax ginseng C. A. Mey., are well known for their potent immunomodulatory effects. However, their precise mechanisms, particularly concerning the "intestinalmetabolism-immune axis", have yet to be fully elucidated. Purpose: This study aims to investigate how ginsenosides protect immune function through the regulation of the gut-metabolism-immune axis. Study design: A CTX-induced immunodeficient mouse model was established to assess the effects of ginsenosides on immune function, gut microbiota, and metabolic pathways. Methods: The immune organ indices (spleen and thymus), levels of immune cytokines (TNF-alpha, IFN-gamma, IL-6, IL-1(3), and immunoglobulins (IgM, IgA) were assessed. Intestinal microbial diversity was analyzed using 16S rRNA sequencing, and metabolomics was employed to identify disruptions in amino acid and lipid metabolic pathways. Spearman correlation analysis and Western blotting were conducted to explore the involvement of the TLR4/ MyD88/NF-kappa B signaling pathway. Results: Ginsenosides significantly restored immune organ indices and enhanced cytokines and immunoglobulins. 16S rRNA sequencing revealed an increase in probiotic levels and a reduction in potentially harmful bacteria, thereby enhancing intestinal microbiota diversity. Metabolomics analysis showed that ginsenosides ameliorated CTX-induced metabolic disorders and stimulated the production of short-chain fatty acids (SCFAs) and bile acids. Western blot analysis confirmed the upregulation of TLR4, MyD88, and NF-kappa B p-p65 expression. Conclusion: This study systematically elucidates the mechanism by which ginsenosides enhance immune function by regulating gut microbiota, restoring metabolic balance, and activating the TLR4/MyD88/NF-kappa B signaling pathway. These findings provide a molecular foundation for the potential use of ginsenosides in the prevention and treatment of immune-related diseases.