title: An experimental study on amelioration of dyslipidemia-induced atherosclesis by Clematichinenoside through regulating Peroxisome proliferator-activated receptor-α mediated apolipoprotein A-I, A-II and C-III.
abstract: Prevention or amelioration the prevalence of atherosclerosis has been an effective strategy in the management of cardiovascular diseases. The aim of the study was to scrutinize the effect of Clematichinenoside (AR) on dyslipidemia-induced atherosclerosis and explore its capability on expression of Peroxisome proliferator-activated receptor-α (PPAR-alpha), apolipoprotein A-I (APOA1) and A-II (APOA2), and suppression of apolipoprotein C-III (APOC3) genes and proteins. In the present study, we investigated atherosclerosis effect of AR using a combination of high-fat diet and balloon injury model in rabbits. The levels of biochemical indicators were evaluated in plasma, liver and HepG2 cells using immunoassay technology. In order to expose the underlying mechanism, we evaluated the regulation of PPAR-alpha, APOA1, APOA2 and APOC3 expressions by AR, and we further evaluated the interactions between them after transfection with shRNA (shPPAR-alpha) and, the action of PPAR-alpha in HepG2 cells. We could find that AR markedly promoted the PPAR-alpha transfer from cytoplasm to nucleus which resulted in the alteration of APOA1, APOA2 and APOC3 expressions in HepG2 cells. Moreover, AR significantly reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) levels, and elevated high-density lipoprotein cholesterol (HDL-C) level, which play an important role in dyslipidemia-induced atherosclerosis. In conclusion, AR ameliorated atherosclerosis via the regulation of hepatic lipid metabolism, and AR also contributed to the activation of PPAR-alpha, APOA1, APOA2 and APOC3. Therefore, AR could be a potential therapeutic agent in the treatment of atherosclerosis.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacochemistry, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Mengchen
authors.initials: M
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yunmanlicpu@hotmail.com.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D016633:Apolipoprotein A-II / Q000378:metabolism*; D053305:Apolipoprotein C-III / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000097:blood
chemical_list: C505693:APOA1 protein, human; C115794:APOA2 protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D053305:Apolipoprotein C-III; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D012503:Saponins; D014280:Triglycerides; C581539:clematichinenoside
keywords: Apolipoproteins; Atherosclerosis; Clematichinenoside; HepG2; Lipids; Peroxisome proliferator activated-receptor-α