Reduction of rat cardiac hypertrophy by osthol is related to regulation of cardiac oxidative stress and lipid metabolism.
The objective of this study was to examine the therapeutic effect of osthol, a coumarin compound isolated from the fruit of Cnidium monnieri (L.) Cusson, on cardiac hypertrophy in rats and investigate its potential mechanisms. The rats with cardiac hypertrophy induced by renovascular hypertension were given osthol orally by gavage for 4 weeks. The results showed that in the osthol 20 mg/kg group, the blood pressure, heart weight index and myocardial malondialdehyde content were lowered (p < 0.001, p = 0.002 and p = 0.025, respectively), the myocardial superoxide dismutase and glutathione peroxidase contents were increased (p < 0.001), and the elevated unesterified fatty acids and triacylglycerols in myocardial tissues were decreased (p = 0.017 and p = 0.004, respectively). At the same time, the myocardial peroxisome proliferator-activated receptor (PPAR)-α and carnitine palmitoyltransferase (CPT)-1a mRNA expressions were increased and the myocardial diacylglycerol acyltransferase (DGAT) mRNA expression was decreased in the osthol 20 mg/kg group (p < 0.001). Osthol treatment was associated with a decreased cross-sectional area of cardiomyocytes (p < 0.001). These findings suggest that osthol may exert a therapeutic effect on cardiac hypertrophy in rats, and its mechanisms may be related to the improvement of myocardial oxidative stress and lipid metabolism via regulation of PPARα-mediated target gene expressions including an increase in CPT-1a mRNA expression and a decrease in DGAT mRNA expression.
Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Feng
F
Zhou
Wen
W
Zhong
Jie
J
Xue
Zhen-lun
ZL
Gu
Mei-lin
ML
Xie
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D031048:Cnidium / Q000737:chemistry; D003374:Coumarins / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D003374:Coumarins; D012333:RNA, Messenger; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D051048:Diacylglycerol O-Acyltransferase; D002334:Carnitine O-Palmitoyltransferase; C046627:osthol