Geniposide against atherosclerosis by inhibiting the formation of foam cell and lowering reverse lipid transport via p38/MAPK signaling pathways

Abstract Geniposide, the main medicinal ingredient of Gardenia jasminoides Ellis, is known to be a resistant agent to atherosclerosis. Some reports its mechanism against atherosclerosis remains completely unclear. Herein, we have investigated the protective effect of geniposide against atherosclerosis as well as clarified the mechanisms related with inhibiting the formation of foam cells and lowering reverse lipid transport via p38/MAPK signaling pathways. Macrophage Raw264.7 was induced by lysophosphatidic acid (LPA) to form foam cell as a cell model. ApoE−/- mice were fed with a high-fat diet for 16 weeks to cause atherosclerosis in carotid artery. After treatment with geniposide, CCK-8, oil red O stain, qRT-PCR and western blot were carried out to explore the effect of geniposide. Morphological changes, histological analyses were used to evaluate atherosclerosis in ApoE–/– mice. Geniposide significantly reduced serum total cholesterol (TC), triglyceride (TG) and LDL cholesterol levels in ApoE−/- mice compared with vehicle control. Meanwhile, geniposide dose dependently inhibited the development of atherosclerosis in ApoE−/- mice. Furthermore, geniposide observably inhibited the formation of foam cells induced by LPA, down-regulated the mRNA and protein levels of SR-A and up-regulated the mRNA and protein levels of ABCA1 or SR-B1 in vitro via inhibition of the p38MAPK and AKT signaling pathways. Our study shows that geniposide protected against atherosclerosis and inhibited the formation of foam cells by regulating the equilibrium on expression of diverse lipid transporters in cytomembrane which related with p38MAPK and AKT signaling pathways. Geniposide is a potential therapeutic drug for atherosclerosis.