title: Wedelolactone Regulates Lipid Metabolism and Improves Hepatic Steatosis Partly by AMPK Activation and Up-Regulation of Expression of PPARα/LPL and LDLR.
abstract: Hyperlipidemia is considered one of the greatest risk factors of cardiovascular diseases. We investigated the anti-hyperlipidemic effect and the underlying mechanism of wedelolactone, a plant-derived coumestan, in HepG2 cells and high-fat diet (HFD)-induced hyperlipidemic hamsters. We showed that in cultured HepG2 cells, wedelolactone up-regulated protein levels of adenosine monophosphate activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPARα) as well as the gene expression of AMPK, PPARα, lipoprotein lipase (LPL), and the low-density lipoprotein receptor (LDLR). Meanwhile, administration of wedelolactone for 4 weeks decreased the lipid profiles of plasma and liver in HFD-induced hyperlipidemic hamsters, including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C). The activation of AMPK and up-regulation of PPARα was also observed with wedelolactone treatment. Furthermore, wedelolactone also increased the activities of superoxidase dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the level of the lipid peroxidation product malondialdehyde (MDA) in the liver, therefore decreasing the activity of alanine aminotransferase (ALT). In conclusion, we provide novel experimental evidence that wedelolactone possesses lipid-lowering and steatosis-improving effects, and the underlying mechanism is, at least in part, mediated by the activation of AMPK and the up-regulation of PPARα/LPL and LDLR.
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, Fujian, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, Fujian, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Peng
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, Fujian, China.
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Zhongshan Hospital, Xiamen, Fujian, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Xu
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, Fujian, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Luo
authors.affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Chiral Drugs, Xiamen, Fujian, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D003374:Coumarins / Q000494:pharmacology*; D006224:Cricetinae; D004789:Enzyme Activation; D005234:Fatty Liver / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D011973:Receptors, LDL / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D003374:Coumarins; D011973:Receptors, LDL; C051122:wedelolactone; D000263:Adenylate Kinase; D008071:Lipoprotein Lipase