Abstract
BackgroundDanshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been used for treating heart disease for several thousand years in China. It has been found that a Danshen and Gegen decoction (DG) exhibiting an anti-atherosclerosis effect, which improves the patients’ heart function recovery. Pre-treatment with DG was reported to have protective effects on myocardium against ischemia/reperfusion injury. In the present study, we aim to investigate the post-treatment effect of DG on ischemic-reperfusion injuries ex vivo or in vitro and the underlying mechanisms involved.MethodsThe rat heart function in an ischemia and reperfusion (I/R) model was explored by examining three parameters including contractile force, coronary flow rate and the release of heart specific enzymes within the heart perfusate. In vitro model of hypoxia and reoxygenation (H/R), the protective effect of DG on damaged cardiomyocytes was investigated by examining the cell structure integrity, the apoptosis and the functionality of mitochondria.ResultsOur results showed that DG significantly improved rat heart function after I/R challenge and suppressed the release of enzymes by damaged heart muscles in a dose-dependent manner. DG also significantly inhibited the death of cardiomyocytes, H9c2 cells, with a H/R challenge. It obviously decreased cell apoptosis, protected the mitochondrial function and cell membrane skeleton integrity on H9c2 cells. The cardio-protection was also found to be related to a decrease in intracellular calcium accumulation within H9c2 cells after I/R challenge.ConclusionThe potential application of DG in treating rat hearts with an I/R injury has been implied in this study. Our results suggested that DG decoction could act as an anti-apoptotic and anti-ion stunning agent to protect hearts against an I/R injury.
Highlights
Danshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been used for treating heart disease for several thousand years in China
The myocardial tissue is typically aerobic and its metabolism is closely dependent upon oxygen availability which is confirmed by the abundance of mitochondria and myoglobin in the cardiomyocytes [1]
Once the blood flow to the myocardial tissue is blocked and the oxygen shortage environment is subsequently induced, serious cardiac damage will happen in the ischemic region for the decrease of energy supply and acidosis inducing by anaerobic glycolysis [3,4], the notable decrease of intracellular pH value and the increase of intracellular calcium ion concentration ([Ca2+]i) [5,6,7]
Summary
Danshen (Salviae Miltiorrhizae Radix) and Gegen (Puerariae Lobatae Radix) have been used for treating heart disease for several thousand years in China. The decrease contractile force or ventricular akinesis for the myocardium damage disturbs the normal blood circulation, which intensifies the heart tissue injury [1,9] In this case, a series of cardiac injury events will happen, such as a decrease in the energy-supplying substances (such as ATP, phocereatin and glycogen), an increase in lactate production and acidosis for anaerobic glycolysis [6,7], an accumulation of the substrates for generating superoxide (O2- ) and hydrogen peroxide, a notable decrease of the intracellular pH value and an increase of intracellular calcium ion concentration ([Ca2+]i) [5,6,7]. Those damage-related factors can directly initiate the myocardium apoptosis pathway to intense cell dysfunction and demise [12,16]
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