title: Elatoside C protects the heart from ischaemia/reperfusion injury through the modulation of oxidative stress and intracellular Ca²⁺ homeostasis.
abstract: BACKGROUND
  We have previously shown that Elatoside C reduces cardiomyocyte apoptosis during ischaemia/reperfusion (I/R). Here, we investigated whether Elatoside C improves heart function in isolated rat hearts subjected to I/R and elucidated the potential mechanisms involved in Elatoside C-induced protection.
  
  
  RESULTS
  Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of Elatoside C. We found that Elatoside C significantly attenuated cardiac dysfunction and depressed oxidative stress induced by I/R. Consistently, Elatoside C prevented I/R-induced mitochondrial dysfunction, which was evident by the inhibition of mitochondrial ROS production, mitochondrial permeability transition pore (mPTP) opening, cytochrome c release from the mitochondria and Bax translocation. Moreover, Elatoside C improved abnormal calcium handling during I/R, including increasing sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) activity, alleviating [Ca(2+)]ER depletion, and reducing the expression levels of ER stress protein markers. All of these protective effects of Elatoside C were partially abolished by the PI3K/Akt inhibitor LY294002, ERK1/2 inhibitor PD98059, and JAK2/STAT3 inhibitor AG490. Further assessment in isolated cardiomyocytes showed that Elatoside C maintained the Ca(2+) transients and cell shortening against I/R.
  
  
  CONCLUSIONS
  Elatoside C protects against cardiac injury during I/R by attenuating oxidative stress and [Ca(2+)]i overload through the activation of both the reperfusion injury salvage kinase (RISK) pathway (including PI3K/Akt and ERK1/2) and the survivor activating factor enhancement (SAFE) pathway (including JAK2/STAT3) and, subsequently, inhibiting the opening of mPTPs.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Min
authors: M
authors: Wang
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunguibo@126.com.
authors: Gui-Bo
authors: GB
authors: Sun
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Jing-Yi
authors: JY
authors: Zhang
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Yun
authors: Y
authors: Luo
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Ying-Li
authors: YL
authors: Yu
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Xu-Dong
authors: XD
authors: Xu
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors: Xiang-Bao
authors: XB
authors: Meng
authors: Harbin University of Commerce, Harbin 150076, Heilongjiang, PR China.
authors: Miao-di
authors: MD
authors: Zhang
authors: Harbin University of Commerce, Harbin 150076, Heilongjiang, PR China.
authors: Wen-Bin
authors: WB
authors: Lin
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: sunsubmit@163.com.
authors: Xiao-Bo
authors: XB
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D006706:Homeostasis / Q000187:drug effects*; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology*
chemical_list: D012503:Saponins; C000601129:elatoside C; D002118:Calcium
keywords: Calcium overload; Elatoside C; Ischaemia/reperfusion; Oxidative stress