Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms.

[BACKGROUND] Metabolic reprogramming is a hallmark of cancer development. By regulating energy and nutrient metabolism, it shapes an immunosuppressive tumor microenvironment (TME) that supports rapid tumor proliferation and promotes cancer progression. Ginsenosides, the major active components of Panax ginseng, have recently been found not only to directly inhibit tumor cell proliferation and induce apoptosis, but also to remodel the TME through metabolic regulation in both tumor and immune cells, thereby enhancing antitumor immune responses. However, the underlying mechanisms have not been fully elucidated.

[PURPOSE] This study systematically summarizes the metabolic targets and regulatory mechanisms of ginsenosides in key pathways of metabolic reprogramming involving glucose, lipid, amino acid, and nucleotide metabolism, aiming to provide a theoretical basis and new perspectives for tumor metabolism-based immunotherapy.

[METHODS] Using "ginsenoside", "glucose metabolism", "Warburg effect", "lipid metabolism", "fatty acid", "cholesterol", "amino acid metabolism", "nucleotide metabolism", " tumor" and combinations of these keywords in PubMed, Web of Science, and CNKI.

[RESULTS] Ginsenosides primarily restore immune cell function by reversing the Warburg effect, suppressing fatty acid synthesis and oxidation, downregulating cholesterol and arachidonic acid metabolism, and inhibiting the depletion of glutamine and tryptophan as well as the catabolism of arginine. In addition, ginsenosides downregulate purine and pyrimidine biosynthesis, thereby limiting tumor cell proliferation.

[CONCLUSIONS] Ginsenosides alleviate the immunosuppressive state of the TME and restore immune effector cell functions through multidimensional metabolic regulation. In the future, it is necessary to conduct further clinical investigations and develop metabolism-targeted ginsenoside delivery systems to ultimately achieve precise cancer therapy.