title: Cyclovirobuxinum D alleviates cardiac hypertrophy in hyperthyroid rats by preventing apoptosis of cardiac cells and inhibiting the p38 mitogen-activated protein kinase signaling pathway.
abstract: OBJECTIVE
  To investigate the underlying mechanisms of cyclovirobuxinum D (Cvb-D) on alleviating cardiac hypertrophy in rats.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into 5 groups: control group; levothyroxine-induced cardiac hypertrophy group (model); levothyroxine-induced cardiac hypertrophy + Cvb-D group (Cvb-D); levothyroxine-induced cardiac hypertrophy + captopril group (captopril); levothyroxine-induced cardiac hypertrophy + SB203580 group (SB203580), n=10 for each group. Rats were daily administered the respective drugs continuously for14 days by gastric gavage. A rat model of cardiac hypertrophy was established by intraperitoneal injection of levothyroxine to investigate whether Cvb-D protects against cardiac hypertrophy by inhibiting the p38 mitogen-activated protein kinase (MAPK) signaling pathway and preventing apoptosis of cardiac cells.
  
  
  RESULTS
  Treatment with Cvb-D significantly deceased left ventricle hypertrophy, improved the histopathology, hemodynamic conditions, and cardiac function in rats with cardiac hypertrophy. Compared with the normal control group, in rats with cardiac hypertrophy, expression of bax in the heart and phospho-p38 MAPK protein levels were significantly up-regulated (P<0.01 or 0.05), whereas the bcl-2 protein level was down-regulated (P<0.01). In contrast, Cvb-D treatment reversed the changes in bax and phospho-p38 MAPK protein levels but increased the bcl-2 protein level (P<0.01 or 0.05), and these effects were similar to those of captopril and SB203580 (a specific p38MAPK inhibitor) treatment. Furthermore, both Cvb-D, captopril and SB203580 reduced mRNA expression of p38α, p38β, c-fos, and c-jun mRNA, and Cvb-D had a stronger effect (P<0.01).
  
  
  CONCLUSIONS
  These results demonstrate that Cvb-D protects against cardiac hypertrophy, which is possibly mediated by prevention of cardiac cell apoptosis and inhibition of the p38MAPK signaling pathway.
authors.affiliation: The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.|Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Jun-Biao
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. zhoujiuyao@tom.com.|Science and Technology Park Co., Ltd., Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. zhoujiuyao@tom.com.
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006980:Hyperthyroidism / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D005227:Fatty Acids; D012333:RNA, Messenger; C524545:cyclovirobuxinum D; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chinese medicine; apotosis; cyclovirobuxinum D; hypertrophic cardiomyopathy; p38 mitogen-activated protein kinase