Piperlonguminine attenuates atherosclerosis in mice via phenotype switching inhibition of vascular smooth muscle cells.

Phenotypic switching of vascular smooth muscle cells (VSMCs) plays diverse roles in the development of atherosclerosis. These cells are a primary contributor to plaque formation and can transition between contractile and synthetic states in response to inflammation or oxidized low-density lipoproteins, exacerbating atherosclerosis. Piperlonguminine (PLG), a bioactive compound obtained from Piper longum L., is commonly used as traditional Mongolian medicine. To elucidate the effects and mechanisms of PLG on atherosclerosis via inhibition of the phenotype switch of VSMCs, we investigated the effects of PLG in the phenotypic transformation, proliferation, and migration of VSMCs. From the view of the symptoms of atherosclerosis, PLG alleviated the pathological changes of atherosclerosis; downregulated total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels; and decreased the levels of inflammatory cytokines. PLG regulated VSMC phenotypic switch proteins and also inhibited the proliferation and migration of VSMCs. Matrix metalloproteinases (MMPs) play a fundamental role in the phenotypic switch of VSMCs. The expression of MMP-2 and MMP-9 was assessed to elucidate the effects of PLG. PLG reduced the expression of MMP-2 and MMP-9 to inhibit the proliferation and migration of VSMCs. The findings collectively illustrate that PLG inhibited the phenotypic transformation, proliferation, and migration of VSMCs, thereby impeding the advancement of atherosclerosis. This inhibition was, in part, linked to reduced MMP-2 and MMP-9 expression.