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GW24-e1859 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 myocardial infarction
  1. Zhu Xinyuan,
  2. Zi-Long Zhang,
  3. Pei Li,
  4. Wen-Yi Liang,
  5. Xue-Ru Feng,
  6. Mei-Lin Liu
  1. Peking University First Hospital

Abstract

Objectives 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 the inhibition of endoplasmic reticulum stress (ERS) and oxidative stress involved in the regulation of apoptosis in cardiac myocytes.

Methods A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Pigs were randomised into 6 study groups: Group S, sham (n = 6); Group C, myocardial infarction controls (n = 8); Group L, MI + low-dose Shenyuan (240 mg/kg•d, n = 6); Group M, MI + medium-dose Shenyuan (320 mg/kg•d, n = 6); Group H, MI + high-dose Shenyuan (400 mg/kg•d, n = 6); Group B, MI + Metoprolol Tartrate (1 mg/kg•d, n = 6). The treatment of Shenyuan or Metoprolol started at one week before MI and continued for another two weeks after MI.

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 the less release of cardiac enzymes and limit of infarct size. Besides, in group H, the levels of MDA, 8-iso-prostaglandin F2a, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, and cleaved caspase-3, and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were increased (p < 0.05). In groups M and L, some results did not reach statistically significant difference. With respect to cardiac function, there was no statistically significant difference between treatment groups and group C.

Conclusions Shenyuan treatment, which started at one week before MI and continued for another two weeks after MI, significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, and then suppressed activation of caspase-3, thus exerting an anti-apoptotic effect in pigs with a large anterior wall MI. This was accompanied by less release of cardiac enzymes, and limit of infarct size. Shenyuan treatment inhibited apoptosis and might have a therapeutic role in improving the natural history of MI.

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