Tanshinone IIA inhibits foam cell formation and alleviates atherosclerosis by regulating the Hedgehog signaling pathway through TRPM2 suppression.

The development of foam cells is crucial in the advancement of atherosclerosis (AS). Tanshinone IIA (Tan IIA), the primary lipophilic component of Salvia miltiorrhiza, has various pharmacological effects. Despite this, the precise role of Tan IIA in AS has not been fully elucidated. In this research, we employed ApoE-/- mice to establish an AS model. Oil Red O and HE staining indicated that Tan IIA obviously reduced plaque areas in both the aorta and aortic arch. Additionally, serum analysis revealed that Tan IIA notably decreased lipid and inflammatory factor levels in AS mice. In vitro studies showed that Tan IIA primarily prevented foam cell formation by enhancing cholesterol efflux rather than increasing lipid uptake. Mechanistic investigations reveal that Tan IIA suppresses the Hedgehog (Hh) signaling pathway by downregulating the expression of transient receptor potential melastatin 2 (TRPM2) and subsequently inhibiting Ca²⁺ influx. This cascade ultimately attenuates foam cell formation and impedes the progression of AS. Overall, this research provides a solid theoretical foundation for the potential application of Tan IIA in the treatment of AS.