Key result
Pretreatment with the combination of paeonol and danshensu significantly reduced myocardial infarct size to 18.64% compared to 33.63% with isoproterenol alone (P<0.001).
Why the study?
Does the combination of paeonol and danshensu prevent isoproterenol-induced myocardial injury in rats?
Does the combination of paeonol and danshensu prevent isoproterenol-induced myocardial injury in rats?
Absolute Event Rate: 18.64% vs 33.63%
p-value: p=<0.001
The combination of paeonol and danshensu provides synergistic cardioprotection against isoproterenol-induced myocardial infarction in rats via antioxidant and anti-apoptotic mechanisms.
Should not change clinical practice for myocardial injury prevention; hypothesis-generating in rat models and requires human trials.
BACKGROUND: Traditional 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. METHODOLOGY: Paeonol (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 FINDINGS: Induction 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/SIGNIFICANCE: This 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.
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Li et al. (2012) studied Isoproterenol-induced myocardial injury (n=40). Paeonol and danshensu combination vs. Isoproterenol alone was evaluated on Myocardial infarct size (p=<0.001). Pretreatment with the combination of paeonol and danshensu significantly reduced myocardial infarct size to 18.64% compared to 33.63% with isoproterenol alone (P<0.001).
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