Pretreatment with a traditional Chinese formula, guanxin II, reduces cardiac apoptosis via the Akt survival pathway in rats with myocardial ischemia.
Guanxin II (GXII) is a traditional Chinese formula to treat coronary heart disease in China. Previous studies indicate cardioprotection of GXII are related to cardiomyocyte apoptosis. Akt is necessary and sufficient for inhibition of apoptosis in cardiomyocytes. Our aim was to examine whether or not the antiapoptotic mechanisms of GXII are related to the Akt pathway. Male Sprague-Dawley rats were randomly assigned to four groups: GXII administered at 2.5 or 0.5 g raw materials/kg, the vehicle control and sham-operated oral 0.9% NaCl. They were pretreated once a day for 15 consecutive days by gavage. Thirty min after the last administration, the left anterior descending coronary artery was occluded to induce myocardial ischemia except for the sham-operated rats. Compared with rats receiving vehicle, those rats pretreated with GXII at 2.5 g/kg significantly reduced infarct size and decrease apoptosis. Furthermore, GXII (2.5 g/kg) significantly activated Akt kinase, increased the Bcl-2/Bax ratio, inhibited cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation. GXII at 0.5 g/kg have no noticeable effect on these parameters. Meanwhile, GXII at 2.5 g/kg did not change myocardial blood flow of ischemic zone, indicating a direct action on cardiomyocytes. These results suggest GXII at 2.5 g/kg ensures the survival of myocardium by enhancing the Akt-mediated antiapoptosis pathway. The findings provide new evidence of the effective and safe therapy with GXII for patients with chronic coronary heart disease.
Laboratory of Ethnopharmacology and Institute of Integrated Medicine, Xiangya Hospital, Central South University, Changsha, China. tcmhuangx59@163.com
Xi
X
Huang
Xue-Ya
XY
Zhang
Feng
F
Qin
Xiao-Yu
XY
Wang
Ping
P
Ren
Zhao-Qian
ZQ
Liu
Hong-Hao
HH
Zhou
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C539574:guanxin No. 2; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9