title: 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 300 mg/kg/day) for 10 weeks. Serum lipid profile was assessed at 0, 4.5, and 10 weeks. 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 24 h, with or without pretreatment with UA (5, 10 or 20 μM) for 16 h, autophagy inhibitor 3-MA 5 mM for 2 h, or SIRT1 inhibitor EX-527 10 μM for 2 h. 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.
authors: Department of Pharmacology, Qingdao University Medical College, Boya Building Room 422, 308 Ningxia Road, Qingdao, 266071, Shandong, China.
authors: Qixiao
authors: Q
authors: Jiang
authors: Department of Pharmacology, Qingdao University Medical College, Boya Building Room 422, 308 Ningxia Road, Qingdao, 266071, Shandong, China.
authors: Ranran
authors: R
authors: Hao
authors: The Institute of Human Nutrition Medical College, 38 Dengzhou Road, Qingdao, 266071, Shandong, China.
authors: Wencheng
authors: W
authors: Wang
authors: Department of Pharmacology, Qingdao University Medical College, Boya Building Room 422, 308 Ningxia Road, Qingdao, 266071, Shandong, China.
authors: Hui
authors: H
authors: Gao
authors: Department of Pharmacology, Qingdao University Medical College, Boya Building Room 422, 308 Ningxia Road, Qingdao, 266071, Shandong, China. cbwang666@126.com.
authors: Chunbo
authors: C
authors: Wang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5 / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity; D008297:Male; D011784:Quail / Q000378:metabolism; D056564:Sirtuin 1 / Q000096:biosynthesis*; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000071187:Autophagy-Related Protein 5; D008077:Lipoproteins, LDL; D056564:Sirtuin 1; D014315:Triterpenes; D000097245:Ursolic Acid; C502778:ATG5 protein, human; C099252:oxidized low density lipoprotein; C447939:SIRT1 protein, human
keywords: Atg5; Atherosclerosis; Autophagy; SIRT1; Ursolic acid