Salvianolic acid monomers against metastasis: Decoding the multilayered interception of EMT, angiogenesis and immune...

Salvianolic acids (SAs), a water‑soluble active component extracted from the traditional Chinese herb Salvia miltiorrhiza, have attracted considerable attention as an anti‑tumor agent. Accumulating evidence demonstrates that SAs potently inhibit tumor‑cell migration, invasion and metastasis through multiple signaling pathways and molecular targets. First, SAs remodel the extracellular matrix and suppress matrix metalloproteinase activities, thereby attenuating the epithelial‑mesenchymal transition and the associated stem‑like properties of cancer cells. Second, SAs block tumor angiogenesis, depriving tumors of essential nutrients and routes for metastasis. Third, SAs reprogram the tumor microenvironment by modulating immune cells, enhancing immune cell infiltration and relieving immunosuppression, ultimately curbing tumor progression. Fourth, SAs target metastatic cellular plasticity and therapy resistance by disrupting cytoskeletal reorganization, impairing cell motility and reversing drug‑resistant phenotypes, thereby enhancing cancer treatment efficacy with reduced toxicity. At the molecular level, SAs suppress the PI3K/AKT, MAPK and TGF‑β1/Smad signaling cascades, thereby diminishing the invasive and migratory capacity of tumor cells. In this review, recent advances in understanding the anti‑metastatic effects and underlying mechanisms of SAs were systematically summarized, the challenges hindering their clinical translation were discussed and future directions that may facilitate their development as a promising anti‑metastatic therapeutic agent were outlined.