SIRT1/Atg5/autophagy are involved in the antiatherosclerosis effects of ursolic acid.

Abstract

The purpose of this study was to investigate the antiatherosclerosis effects of ursolic acid (UA) in high-fat diet-fed quails (Coturnix coturnix) and potential mechanism. Quails were treated with high-fat diet (14% pork oil, 1% cholesterol w/w) with or without UA (50, 150, or 300mg/kg/day) for 10 weeks. Serum lipid profile was assessed at 0, 4.5, and 10weeks. After 10 weeks, serum antioxidant status and morphology of aorta were assessed. Additionally, human umbilical vein endothelial cells (HUVECs) were exposed to 100 μg/ml oxidized low-density lipoprotein (ox-LDL) for 24h, with or without pretreatment with UA (5, 10 or 20μM) for 16h, autophagy inhibitor 3-MA 5mM for 2h, or SIRT1 inhibitor EX-527 10μM for 2h. Cell viability and oxidative stress status were assessed and autophagy status was determined. Acetylation of lysine residue on Atg5 was assessed with immunoprecipitation. In results, high-fat diet negatively affected serum lipid profile and antioxidant status in quails and induced significant histological changes. Cotreatment with UA remarkably alleviated such changes. In HUVECs, ox-LDL treatment induced significant cytotoxicity along with oxidative stress, while UA cotreatment alleviated such changes significantly. UA treatment induced autophagy, enhanced SIRT1 expression, and decreased acetylation of lysine residue on Atg5. Cotreatment with 3-MA or EX-527 effectively abolished UA's protective effects. In summary, UA exerted antiatherosclerosis effects in quails and protected HUVECs from ox-LDL induced cytotoxicity, and the mechanism is associated with increased SIRT1 expression, decreased Atg5 acetylation on lysine residue, and increased autophagy.