title: In vivo and in vitro protective effects of pentamethylquercetin on cardiac hypertrophy.
abstract: OBJECTIVE
  To investigate the in vivo and in vitro protective effects of pentamethylquercetin (PMQ), a member of polymethoxy flavonoids (PMFs), on cardiac hypertrophy.
  
  
  METHODS
  An in vivo cardiac hypertrophy model established by abdominal aorta banding technique in rats was treated with PMQ in increasing dosages (2.5, 5, and 10 mg x kg(-1) x d(-1)). An in vitro cardiomyocyte hypertrophy model was induced by treating neonatal cardiomyocytes with endothelin-1 (ET-1, 0.1 μM). An in vitro fibrosis model was developed in cardiac fibroblasts by aldosterone (Ald, 20 nM) and treated with PMQ (0.3, 1, 3 and 10 μM). Hemodynamic, morphological, histological, and biochemical changes were evaluated at corresponding time points.
  
  
  RESULTS
  The abdominal aorta constriction (AAC) rats demonstrated a significantly elevated blood pressure and profound systolic and diastolic cardiac dysfunction. The resultant cardiac hypertrophy and heart failure were characterized by a significant increase in the heart and lung indices (3.51 ± 0.30 vs 2.35 ± 0.24, 5.58 ± 0.85 vs 3.94 ± 0.54; both P < 0.01), cardiomyocyte cross-sectional areas (153 ± 33% vs 100 ± 5%, P < 0.01) and myocardial fibrosis (9.09 ± 1.30% vs 1.49 ± 0.20%, P < 0.01) with concomitant elevation of B-type natriuretic peptide and cardiac collagen mRNA level. Daily oral administration of PMQ (2.5, 5, and 10 mg/kg for 7 weeks) prevented the foregoing histology, gene and protein changes secondary to AAC procedure. In addition, the up-regulated inflammation factors such as TNF-α and IL-6, and the down-regulated PPAR α and PPAR β were normalizd by PMQ treatment.
  
  
  CONCLUSIONS
  PMQ has significant protective effects on cardiac hypertrophy through up-regulating the mRNA and protein levels of PPAR α and PPAR β involved in the process of inflammation response and cardiac fibrosis.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Han
authors.forename: Wei-Qin
authors.initials: WQ
authors.lastname: Yang
authors.forename: Man-Wen
authors.initials: MW
authors.lastname: Jin
mesh_terms: D000450:Aldosterone / Q000009:adverse effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D019332:Endothelin-1; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D048068:PPAR-beta / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C548139:3,3',4',5,7-pentamethylquercetin; D002316:Cardiotonic Agents; D019332:Endothelin-1; D015850:Interleukin-6; D047493:PPAR alpha; D048068:PPAR-beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D003094:Collagen; D011794:Quercetin