Total saponins from Aralia taibaiensis protect against myocardial ischemia/reperfusion injury through AMPK pathway.
It was previously shown that total saponins extracted from Aralia taibaiensis (sAT) have potent antioxidant activities for treating diabetes mellitus and attenuate d-galactose-induced aging. Since diabetes mellitus and aging are closely associated with cardiac dysfunction, particularly ischemic heart disease, sAT may have potential protective activity against myocardial ischemia/reperfusion injury (MI/RI). However, the anti-MI/RI effects of sAT have yet to be examined, and the possible molecular mechanisms remain to be determined. The present study was undertaken to investigate the anti-MI/RI activities of sAT and to elucidate the mechanisms underlying these effects in rats using TUNEL and Hoechst 33258 staining. The results confirmed the cardioprotective effects in vivo and elucidated the potential molecular mechanisms of sAT in vitro. Pretreatment with sAT significantly reduced infarct size, decreased the levels of lactate dehydrogenase and creatine kinase in the serum and blocked apoptosis. In addition, sAT inhibited A/R-induced apoptosis by decreasing DNA strand breaks, caspase-3 activity and cytochrome c release in H9c2 cells. Furthermore, sAT markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase and elevated the Bcl2/Bcl-2-associated X protein ratio. These effects were blocked by compound C. The results suggested that sAT pretreatment exerts protective effects on myocardial cells in vitro and in vivo against MI/RI-induced apoptosis by activating AMPK pathway.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Jiajia
J
Yan
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Jialin
J
Duan
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Xiaoxiao
X
Wu
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Chao
C
Guo
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Ying
Y
Yin
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Yanrong
Y
Zhu
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Tianxin
T
Hu
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Guo
G
Wei
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Aidong
A
Wen
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Miaomiao
M
Xi
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D027983:Aralia / Q000737:chemistry*; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003402:Creatine Kinase / Q000097:blood; D045304:Cytochromes c / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D055372:AMP-Activated Protein Kinases; D003402:Creatine Kinase; D053148:Caspase 3