Ethanol extract from Epimedium brevicornum attenuates left ventricular dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with congestive heart failure

Abstract

Epimedium, a traditional Chinese herb, has been used for the remedy of coronary heart disease, impotence and osteoporosis in traditional oriental medicine. However, despite extensive pharmacological studies, the molecular mechanism of the anti-heart failure effect of epimedium is little known. In the present study, we investigated the pharmacological action mechanism of ethanol extract of epimedium (EPI-ext) on isoproterenol-induced congestive heart failure (CHF) in rats. Isoproterenol administration resulted in severe heart failure, as shown by the increased levels of left ventricular (LV) weight index and heart rate, as well as LV end diastolic pressure, and by the decreased levels of LV systolic pressure, maximal rate of LV pressure rise, and maximal rate of LV pressure decline. EPI-ext dose-dependently reversed the changes of these cardiac morphometric and hemodynamic parameters. In addition, EPI-ext significantly inhibited the serum levels of tumor necrosis factor alpha, norepinephrine, angiotensin II and brain natriuretic peptide in rats with CHF and improved the histological changes including cadiocyte hypertrophy, cadiocyte degeneration, inflammatory infiltration, and cardiac desmoplasia. Furthermore, the expression and activities of matrix metalloproteinase-2 and -9, which regulate collagen production, were also blocked by EPI-ext. Moreover, myocardial apoptosis was remarkably attenuated by EPI-ext through the regulating Bcl-2/Bax axle. In conclusion, EPI-ext ameliorates LV dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with CHF.