Cardioprotective effects of saponins from Panax japonicus on acute myocardial ischemia against oxidative stress-triggered damage and cardiac cell death in rats.
OBJECTIVE
To study the cardioprotective effects of saponins from Panax japonicus (SPJ) on acute myocardial ischemia injury rats induced by ligating of the left anterior descending branch (LAD), on the basis of this investigation, the possible mechanism of SPJ was elucidated.


METHODS
SPJ was identified by high performance liquid chromatography-evaporative light scattering detection. Male Sprague-Dawley rats (200-220g) were randomly divided into four groups: sham-operated, LAD, LAD+l-SPJ (SPJ, 50mg/kg/day, orally) and LAD+h-SPJ (SPJ, 100mg/kg/day, orally). Before operation, the foregoing groups were pretreated with homologous drug once a day for 7 days, respectively. After twelve hours in LAD, the cardioprotective effects of SPJ were evaluated by infarct size, biochemical values, hemodynamic, and histopathological observations and the antioxidative and antiapoptotic relative gene expressions.


RESULTS
SPJ significantly improved heart function and decreased infarct size; remarkably decreased levels of serum lactate dehydrogenase, creatine kinase, xanthine oxide and malondialdehyde content, increased contents of serum total antioxidant capacity, superoxide dismutase (SOD), glutathione peroxidase, catalase; quantitative real-time PCR results showed that SPJ might markedly reverse the down-regulated mRNA expressions of the SOD1, SOD2 and SOD3, ameliorate the increased Bax and caspase-3 mRNA expressions and decreased Bcl-2 mRNA expression and ratios of Bcl-2 to Bax. Histopathological observations provided supportive evidence for biochemical analyses, and with the dose of SPJ increasing, the aforesaid improvement became more and more strong.


CONCLUSIONS
The studies demonstrated that in ischemic myocardium, oxidative stress caused the overgeneration and accumulation of reactive oxygen species (ROS), which was central of cardiac ischemic injury. SPJ exerted beneficially cardioprotective effects on myocardial ischemia injury rats, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial ischemia injury and cardiac cell death.
Laboratory of Chinese Drug Pharmacology, College of Medical Sciences, China Three Gorges University, Yichang, PR China.
Haibo
H
He
Jia
J
Xu
Yuanqing
Y
Xu
Changcheng
C
Zhang
Hongwu
H
Wang
Yumin
Y
He
Ting
T
Wang
Ding
D
Yuan
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014970:Xanthines / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012503:Saponins; D014970:Xanthines; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D053148:Caspase 3