Regulation of antioxidant system, lipids and fatty acid β-oxidation contributes to the cardioprotective effect of sodium tanshinone IIA sulphonate in isoproterenol-induced myocardial infarction in rats

• We employed ISO-treated rats to ascertain the strong protective action of STS, and to elucidate its potential mechanisms.
• STS possesses the property to enhance endogenous antioxidant system by up-regulation of HO-1 expression through the ERK/Nrf2 pathway.
• STS exerts the beneficial action to modulate dyslipidemia by down-regulation of CPT1 expression through the AMPK/ACC pathway.

ObjectiveMyocardial infarction (MI) is a cause of high morbidity and mortality in the world. Sodium tanshinone IIA sulphonate (STS) has been well used in Oriental medicine for treating cardiovascular diseases, however, the underlying mechanisms remain unclear. Alterations of circulating lipid profiles, increased fatty acid β-oxidation and oxidative stress play most important roles in the pathogenesis of MI. The present study aims to elucidate whether STS possesses cardioprotective effect against MI driven by isoproterenol (ISO), and to investigate its potential mechanisms of action.MethodsMI was induced by subcutaneous injection of ISO (85 mg/kg at interval of 24 h for 2 consecutive days) to rats. The rats were randomly divided into 6 groups: (1) control; (2) ISO; (3) STS (16 mg/kg) +control; (4–6) STS (16, 8, 4 mg/kg) +ISO.ResultsOur study showed that STS could ameliorate cardiac dysfunction and variation of myocardial zymogram, up-regulate antioxidant systems, and maintain the levels of circulating lipids driven by supramaximal doses ISO as well. Moreover, modulation of redox-sensitive extracellular signal-regulated kinase1/2 (ERK1/2)/Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and AMP-activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC)/carnitine palmitoyltransferase (CPT) 1 pathways were involved in STS induced cardioprotection.ConclusionsSTS exerts strong favorable cardioprotective action. Additionally, the properties of STS, such as anti-dyslipidemia, anti-oxidant and inhibition of fatty acid β-oxidation, may be the mechanisms underlying the observed results.