title: Puerarin inhibits angiotensin II-induced cardiac hypertrophy via the redox-sensitive ERK1/2, p38 and NF-κB pathways.
abstract: OBJECTIVE
  To investigate the effects of puerarin (Pue), an isoflavone derived from Kudzu roots, on angiotensin II (Ang II)-induced hypertrophy of cardiomyocytes in vivo and in vitro.
  
  
  METHODS
  C57BL/6J mice were infused with Ang II and treated with Pue (100 mg·kg(-1)·d(-1), po) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were assessed. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were determined, and heart morphometry was assessed. Expression of fetal-type genes (ANP, BNP and β-MHC) in left ventricles was measured using semi-quantitative RT-PCR. Mouse primary cardiomyocytes were treated with Pue (50, 100, 200 μmol/L), then exposed to Ang II (1 μmol/L). ROS level was examined with flow cytometry, the binding activity of NF-κB was determined using EMSA. Western blot was used to measure the levels of ERK1/2, p38 and NF-κB pathway proteins. [(3)H]leucine incorporation was used to measure the rate of protein synthesis.
  
  
  RESULTS
  Oral administration of Pue significantly suppressed Ang II-induced increases in the myocyte surface area, HW/BW, LVW/BW, SBP and left ventricular wall thickness. Furthermore, Pue significantly suppressed Ang II-induced increases in ANP, BNP and β-MHC expression in the left ventricles in vivo. Treatment of cardiomyocytes with Pue (50-500 μmol/L) did not affect the viability of cardiomyocytes in vitro. Pretreatment of cardiomyocytes with Pue dose-dependently inhibited Ang II-induced increases in ROS production, NF-κB binding activity, protein synthesis and cell breadth. Furthermore, pretreatment with Pue significantly suppressed Ang II-induced activation of ERK1/2, p38 and the NF-κB pathway proteins and the expression of ANP and β-MHC in cardiomyocytes. The positive drug valsartan exerted similar effects on Ang II-induced cardiac hypertrophy in vivo and in vitro.
  
  
  CONCLUSIONS
  Pue attenuates Ang II-induced cardiac hypertrophy by inhibiting activation of the redox-sensitive ERK1/2, p38 and the NF-κB pathways.
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: The 4th Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Shi-qi
authors.initials: SQ
authors.lastname: Pan
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Shi-fen
authors.initials: SF
authors.lastname: Pan
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Xiu-min
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Qi-yang
authors.initials: QY
authors.lastname: He
mesh_terms: D000284:Administration, Oral; D000804:Angiotensin II; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D014463:Ultrasonography; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D020257:Ventricular Remodeling / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D007529:Isoflavones; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D014633:Valine; C033607:puerarin