title: Danhong injection attenuates isoproterenol-induced cardiac hypertrophy by regulating p38 and NF-κb pathway.
abstract: BACKGROUND
  Danhong injection (DHI), derived from Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Salvia militiorrhiza Bunge), is an extensively-used Chinese material standardized clinical product for treatment of cardiovascular diseases.
  
  
  OBJECTIVE
  Cardiac hypertrophy (CH) is an adaptive response of cardiomyocytes. Long-lasting cardiac hypertrophy results in the loss of compensation by cardiomyocytes which could ultimately develop into heart failure. In the present study, we aimed to investigate the effect and exact mechanisms of DHI on isoproterenol (ISO)-induced CH.
  
  
  METHODS
  H9c2 cells and male Wistar rats were stimulated by ISO in the present study to establish CH models in vitro and in vivo. CCk-8 assay, Western blot, real time-polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA) and Echocardiography were used in the present study.
  
  
  RESULTS
  DHI significantly attenuated ISO-induced CH of H9c2 cells (p<0.01). DHI decreased ISO-induced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) elevation both at the mRNA and protein levels (p<0.05 and p<0.01, respectively). Western blot showed that DHI down-regulated the phosphorylation of p38. Furthermore, we found that DHI inhibited the nuclear translocation and activation of NF-κb. Echocardiography from ISO-induced CH rats showed that DHI significantly decreased left ventricle (LV) mass, the thickness of the LV end-systolic posterior wall (LVPWs), and the LV end-diastolic posterior wall (LVPWd) elevated by ISO (p<0.01 and p<0.05, respectively).
  
  
  CONCLUSIONS
  These data demonstrate that DHI might exert anti-cardiac hypertrophic effects by regulating p38 and NF-κb pathway.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: haoping_mao@126.com.
authors.forename: Hao-Ping
authors.initials: HP
authors.lastname: Mao
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: wangxingye420@163.com.
authors.forename: Xing-Ye
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: 1083747849@qq.com.
authors.forename: Yun Hang
authors.initials: YH
authors.lastname: Gao
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Yan-Xu
authors.initials: YX
authors.lastname: Chang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: 18502295944@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: nzc601@sina.com.
authors.forename: Zi-Chang
authors.initials: ZC
authors.lastname: Niu
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: aijuqing1987@163.com.
authors.forename: Ju-Qing
authors.initials: JQ
authors.lastname: Ai
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, and Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: gaoxiumei@tjutcm.edu.cn.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Gao
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000188:drug therapy*; D031187:Carthamus tinctorius / Q000737:chemistry*; D002460:Cell Line; D035264:Flowers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D048051:p38 Mitogen-Activated Protein Kinases; D007545:Isoproterenol
keywords: Cardiac hypertrophy; Danhong injection; NF-κb; p38