The Anti-Malarial Drug Artesunate Attenuates Cardiac Injury in a Rodent Model of Myocardial Infarction.

Abstract

Ischaemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v) and patients with severe malaria (2.4 mg/kg i.v). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischaemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA. We report here for the first time that the administration of artesunate at the onset of reperfusion attenuates the myocardial injury associated with I/R. The observed beneficial effects of artesunate are associated with i) activation of the PI3K/Akt/ERK 1/2 (RISK) pathway, ii) activation of eNOS, iii) inhibition of GSK-3β, iv) inhibition of NF-κB, and v) activation of the STAT3 (SAFE) pathway. In conclusion, as artesunate has an excellent safety profile, the above data should stimulate clinical trials in patients with acute coronary syndromes.