Cardioprotection of Asperosaponin X on experimental myocardial ischemia injury

Background: Asperosaponin X was isolated from the roots of Dipsacus asper. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effects of Asperosaponin X in vivo and elucidated the potential mechanism in vitro. Results: Asperosaponin X significantly attenuated hypoxia-induced cytotoxicity in a concentration-dependent manner in H9c2 cells. Treatment of H9c2 cells with Asperosaponin X 5 mu M or 10 mu M blocked TNF-alpha-induced nuclear factor kappaB (NF-kappa B) phosphorylation by blocking HMGB1 expression. Treatment of rats with Asperosaponin X 10 mg/kg, (i.v.) protected the animals from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics and reduction of myocardial damage severity. Treatment with Asperosaponin X also lowered serum levels of pro-inflammatory factors and reduced High mobility group box-1 protein (HMGB1), phosphorylated I kappa B-alpha and NF-kappa B expression in ischemic myocardial tissue. Additionally, continuous i.v. of Asperosaponin X 14 days attenuated cardiac remodeling. Conclusions: These protective effects suggested that Asperosaponin X may be due to block of myocardial inflammatory cascades through an HMGB1-dependent NF-kappa B signaling pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.