title: Icariin Attenuates High-cholesterol Diet Induced Atherosclerosis in Rats by Inhibition of Inflammatory Response and p38 MAPK Signaling Pathway.
abstract: Icariin is a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim and has been reported to be effective for the treatment of a variety of cardiovascular diseases. The aim of the present study was to investigate the effect and mechanism of icariin on atherosclerosis (AS) using a high-cholesterol diet (HCD)-induced rat model. Seventy male Wistar rats were divided into five groups: 20 in the control group, 20 in the AS group, 10 in the simvastatin group, 10 in the low-dose icariin group, and 10 in the high-dose icariin group. A HCD and vitamin D3 were administered to establish AS rat model. The five groups of rats received daily intragastric administration of normal saline, simvastatin, or icariin (30 mg/kg/d, 60 mg/kg/d) for 4 weeks. The levels of blood lipids, superoxide dismutase (SOD), and malonaldehyde (MDA) were measured. The mRNA levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were analyzed by real-time RT-PCR, and the serum levels of IL-6 and TNF-α were measured using ELISA kit. In addition, the expression of phosphorylated p38 (p-p38) MAPK was detected by Western blot analysis. The results indicated that AS rat models were successfully constructed. In the AS group, the levels of blood lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), and MDA were significantly increased, while high-density lipoprotein-cholesterol (HDL-C) and SOD were significantly decreased, compared with those in the control group. However, icariin succeeded in improving these biochemical parameters towards the normal values in the control group. In the simvastatin group and the icariin groups, the serum levels of IL-6 and TNF-α and the related tissue mRNA levels, as well as the expression of p-p38 MAPK, were markedly reduced compared with the AS group. In conclusion, the present study indicated that icariin inhibited the HCD-induced dyslipidemia in rats, the mechanisms may be associated with the anti-inflammation, anti-oxidative stress, and downregulation of p-p38 MAPK by icariin.
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.|School of Pharmaceutics and Food Science, Tonghua Normal University, Tonghua, Jilin, 134002, People's Republic of China.
authors: Yanwu
authors: Y
authors: Hu
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.
authors: Bo
authors: B
authors: Sun
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.
authors: Kai
authors: K
authors: Liu
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.
authors: Mengtong
authors: M
authors: Yan
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.
authors: Yang
authors: Y
authors: Zhang
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China.
authors: Chunsheng
authors: C
authors: Miao
authors: Department of Experimental Pharmacology and Toxicology, School of Medicine, Jilin University, Fujin Road 1266, Changchun, Jilin, 130021, People's Republic of China. renlqjlu@163.com.
authors: Liqun
authors: L
authors: Ren
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000139:chemically induced / Q000188:drug therapy*; D002784:Cholesterol / Q000009:adverse effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D050171:Dyslipidemias / Q000188:drug therapy / Q000517:prevention & control*; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008055:Lipids / Q000097:blood; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D015850:Interleukin-6; D008055:Lipids; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002784:Cholesterol; D019821:Simvastatin; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases; C056599:icariin
keywords: atherosclerosis; dyslipidemia; icariin; inflammation; oxidative stress; p38 MAPK