Garlic extract diallyl sulfide protects against dilated cardiomyopathy through inhibition of oxidative stress and apoptosis in mice
Abstract Background: Diallyl sulfide (DAS) is an active ingredient in garlic that is induced when the garlic is chopped and ground. DAS has been found to act as a competitive inhibitor of CYP2E1, which is a member of the cytochrome P450 enzyme family and catalyses the metabolism of various substrates.CYP2E1 is upregulated in multiple heart diseases and causes damage mainly through the production of ROS. In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and CYP2E1 knockdown can attenuate the pathological development of DCM. Nevertheless, Targeted inhibition of CYP2E1 for the treatment of dilated cardiomyopathy (DCM) remain limited. The aim of this study was to investigate the therapeutic effect of DAS on cardiomyopathy and its possible molecular mechanisms, and provide new clues and approaches for the clinical treatment of cardiomyopathy and heart failure.Methods: Echocardiography were performed to identify mouse heart function and structure. histological analysis and RT-PCR were conducted to investigate that improved Myocardial morphology and fibrosis and measurement of reactive oxygen species (ROS) and tunel Assay were used to detected DAS inhibit ROS production and myocyte apoptosis in cTnTR141W DCM mice. Western Blot were performed to investigate the mechanism of apoptosis pathway.Results: Diallyl sulfide (DAS), a competitive inhibitor of CYP2E1, improves the typical DCM phenotype, including chamber dilation, wall thinning, fibrosis, poor myofibril organization and decreased ventricular blood ejection, by inhibiting ROS production and myocyte apoptosis in cTnTR141W DCM mice.Conclusions: Our results suggest that inhibition of CYP2E1 might be a valuable therapeutic strategy to control the development of heart diseases associated with CYP2E1 overexpression. Moreover, the development of DAS analogues with superior inhibitory properties and lower substrate potential for CYP2E1 might be beneficial for patients with heart disease.