Synergistic Regulation of Glucolipid Metabolism by Ginseng Polysaccharides and Ginsenosides: Divergent Microbiota Modulation and Convergent Activation of Intestinal Gluconeogenesis

Abstract

Ginseng polysaccharides (GPS) and ginsenosides are two major bioactive components of Panax ginseng, both exhibiting regulatory effects on glucolipid metabolism. Traditional research has focused on individual components, but recent evidence suggests that they may exert synergistic effects mediated by the gut microbiota [1,2]. This review systematically summarizes the mechanisms by which GPS and ginsenosides cooperatively regulate glucolipid metabolism via the gut–organ axis. The gut– organ axis is defined as the bidirectional communication network linking the gut microbiota (via its metabolites, such as short‑chain fatty acids and succinate) to distal organs (liver, pancreas, and brain). The available evidence indicates that GPS act as prebiotics, modulating gut microbiota composition, promoting short‑chain fatty acids (SCFAs) production, and enhancing the biotransformation of ginsenosides [1,6]. Ginsenosides are metabolized by the gut microbiota into highly active metabolites (e.g., Compound K) and differentially enrich Proteobacteria and succinate [2,8]. GPS and ginsenosides jointly activate intestinal gluconeogenesis (IGN) through complementary pathways (SCFAs via FFAR2/FFAR3, succinate via SUCNR1), and the resulting portal vein glucose signal further influences systemic energy homeostasis via the gut‑liver and gut‑brain axes [2,8]. This "divergent microbiota modulation–convergent target engagement" synergistic pattern provides a mechanistic explanation for the multi‑component metabolic regulation of ginseng and offers a new mechanistic perspective for the health management of metabolic diseases.