Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2pathway.
Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2(cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2pathway.
Department of Pharmacology, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004, China; Ningxia Hui Medicine Modern Engineering Research Center and Collaborative Innovation Center, Ningxia Medical University, Yinchuan 750004, China.
Ru
R
Zhou
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Qingbin
Q
Xu
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Yehua
Y
Xu
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Aiqin
A
Xiong
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
Yang
Y
Wang
Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750004, China. Electronic address: xu-qb@163.com.
Ping
P
Ma
D000318:Adrenergic beta-Agonists / Q000633:toxicity; D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000502:physiology*; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D011807:Quinolizines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000093842:Matrines
D000318:Adrenergic beta-Agonists; D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D051546:Cyclooxygenase 2; D011464:Epoprostenol; D007545:Isoproterenol; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines
Cyclooxygenase-1; Cyclooxygenase-2; Cytosolic phospholipase A(2); Heart failue; Isoproterenol; Oxymatrine; Prostacyclin synthase