Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction

摘要

Ethnopharmacological relevance: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis. Materials and methods: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kgd, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kgd, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kgd, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kgd, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI. Results: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P<0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P<0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C. Conclusion: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.