PROTECTIVE EFFECTS OF LEONURINE IN NEONATAL RAT HYPOXIC CARDIOMYOCYTES AND RAT INFARCTED HEART

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Abstract
1. Previous studies have shown that extracts of Herba leonuri, predominantly containing the phytochemical components leonurine and stachydrine, provide protective effects in the ischaemic myocardium by acting as free radical scavengers and inhibiting the formation of reactive oxygen species. 2. The present study was designed to investigate the cardioprotective effects of 10(-6) mol/L leonurine on neonatal rat cardiomyocytes treated with hypoxia plus serum deprivation, a component of ischaemia, and to determine the mechanisms underlying the protective effects with regard to cardiac anti-oxidant enzymes and apoptosis genes. Cardiomyocytes were treated with leonurine 8 h prior to exposure to hypoxia. In addition, we investigated the effects of 7.5 and 15 mg/kg leonurine, administered to rats i.p. for 7 days prior to left coronary artery ligation, on subsequent infarct size of the ischaemic heart. 3. Leonurine significantly increased the viability of cardiomyocytes injured by hypoxia. In the leonurine-treated group, gene expression levels of pro-apoptotic genes, namely Bax and Fas, were significantly downregulated (by 0.95- and 0.72-fold, respectively; P < 0.001) compared with the hypoxic control group, whereas the expression of Bcl-2 and Bcl-xl was upregulated following leonurine treatment (by 1.03- and 1.07-fold, respectively; P < 0.05). Correspondingly, leonurine treatment increased Bcl-2 protein levels and decreased Bax protein levels. Assays investigating cardiac anti-oxidant enzymes provided further evidence for a protective effect of leonurine, as indicated by the induction of the anti-oxidant enzymes superoxide dismutase and catalase. Furthermore, leonurine decreased infarct size in ischaemic rat heart. 4. The results of the present study suggest that the mechanisms of action of leonurine in hypoxic neonatal rat cardiomyocytes and infarcted rat heart may be related to its anti-oxidant and anti-apoptotic properties.