Mechanistic insights on mogrosides as bifunctional regulators of metabolic reprogramming and immune modulation in tumor microenvironment

Metabolic reprogramming and immune evasion are interconnected hallmarks of cancer that sustain tumor progression and therapeutic resistance. This review summarizes current mechanistic evidence supporting the therapeutic potential of mogrosides, derived from the fruits of Siraitia grosvenorii , as multi-functional agents with dual roles in regulating tumor metabolism and immune responses. Mechanistically, mogrosides are potent AMPK activators that attenuate the Warburg effect, suppress PI3K/AKT/mTOR signaling, and inhibit de novo lipogenesis. Also, mogrosides suppress lactate accumulation within the tumor microenvironment. In parallel, they modulate immune responses through inhibition of STAT3 and NF-κB signaling pathways, resulting in reduced pro-inflammatory cytokine production and decreased PD-L1 expression. Additionally, mogrosides interfere with oncogenic signaling cascades including JAK/STAT3 and MAPK/ERK that regulate proliferation and survival. They further suppress epithelial–mesenchymal transition and matrix metalloproteinase expression, limiting metastatic potential. By simultaneously targeting metabolic plasticity and immune suppression, mogrosides represent promising adjuvant candidates in cancer therapy; however, further clinical investigations are required to validate their translational potential.