Gypenoside granules alleviate vascular smooth muscle cell phenotypic switching in atherosclerosis through impeding MAPK/KLF4 pathway

• Gypenosides granules attenuated atherosclerosis progression. • Gypenosides granules enhanced plaque stability. • Gypenosides granules inhibited phenotypic switching of VSMC. • Gypenosides granules inhibited MAPK/KLF4 pathway. Phenotypic switching of vascular smooth muscle cells (VSMCs) is crucial in atherosclerosis. Gypenoside granules, used clinically for hyperlipidemia, show significant atheroprotective effects, but their impact on VSMC phenotypic switching is unclear. This study evaluated the effects and mechanisms of gypenoside granules on VSMC phenotypic switching. Using ApoE −/− mice on a high-fat diet, the study found that gypenoside granules reduced blood lipid levels, decreased necrotic core areas, increased fibrous cap thickness, and inhibited inflammation. In PDGF-BB-induced VSMCs, gypenoside granules suppressed phenotypic switching, proliferation, and migration by downregulating KLF4 expression. The beneficial effects were reversed by KLF4 overexpression. HPLC analysis identified ten key components in the granules. These findings suggest that gypenoside granules may alleviate atherosclerosis by modulating the MAPK/KLF4 pathway and could serve as an alternative treatment for the disease.