Abstract
BackgroundTraditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms.MethodologyPaeonol (80 mg kg−1) and danshensu (160 mg kg−1) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg−1) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg−1) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed.Principal FindingsInduction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups.Conclusions/SignificanceThis study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.
Highlights
Ischemic heart disease (IHD) is the most serious crimes against human life, claiming 17 million lives per year [1]
The mean body weight of rats at the end of experiment period in all experimental groups had no significant change (Table 1), ISO treated rats showed a slight reduction in body weight which was not significant
Rats administered with ISO showed a significant (P,0.001) increase in the level of thiobarbituric acid reactive substances (TBARS) while there was a significant (P,0.001) decrease in GSH, superoxide dismutase (SOD), CAT, glutathione peroxidase (GPx), glutathione reductase (GR) and GST as compared to control groups
Summary
Ischemic heart disease (IHD) is the most serious crimes against human life, claiming 17 million lives per year [1]. Myocardial infarction (MI) is a common and life-threatening manifestation of IHD. It occurs when myocardial ischemia surpasses the critical threshold level for an extended time, resulting in irreversible necrosis of the myocardium [3]. It has been suggested that oxidative stress produced by free radicals or reactive oxygen species (ROS), as evidenced by marked increase in production of lipid peroxidative products associated with decreased levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), plays a major role in myocardial damage during MI [5]. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms
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