Pharmacological Mechanisms Involved In Myocardioprotective, Serum Lipid-regulatory And Vasorelaxant Actions Of Puerarin

1 Cardioprotective Effect of Puerarin on Isoproterenol-mediated Myocardial Injury in RatsIn China, Puerarin, one of the bioactive isoflavones isolated from Pueraria lobata (Willd.) Ohwi, has been widely used in treatment of cardiovascular diseases in clinical settimg. It has been demonstrated to have prominent pharmacological effects on myocardial infarction, however, in which mechanisms involved have not been totally elucidated. Cycooxygenase-2 (COX-2) and nitric oxide synthase (NOS) play important roles in myocardial infarction. We hypothesize that the cardioprotection of puerarin partly benefits from its regulation of NO system that is NOS isoforms-specific and COX-2. A rat model of acute myocardial injury is induced by subcutaneous injection of isoproterenol (ISO, 150 mg /kg/day for three days). In the therapeutic group, puerarin (100 mg/kg/day) was intraperitoneally injected 7 days prior to isoproterenol administration and the same dose was continued during isoproterenol administration. 24 hours after the last ISO administration, the myocardial state was demonstrated by electrocardiography in Lead II , serum LDH and CK activity, the content of MDA and left ventricular weight/body weight ratio. Left ventricular NOS isoforms and COX-2 levels were determined by western blotting or real-time RT-PCR. ST-segment elevation, increase of serum LDH and CK activity and high mortality were detected in rats only injected with isoproterenol. Whereas, pre-and co-treatment of puerarin can restore them normal. For the gene expression of three isoforms NOS, nNOS (neuronal), iNOS (inducible) and eNOS (endothelial), puerarin administration prevented the downregulation of eNOS level induced by ISO. There was no significant effect on the downregulation of nNOS and the upregulation of iNOS. Similar results were obtained from the Western blot analysis. For the inflammatory pathway, both COX-2 and tumor necrosis factor-alpha...