Antioxidant activities of aqueous leaf extracts of Toona sinensis on free radical-induced endothelial cell damage

Ethnopharmacological relavence: In Taiwan, Toona sinensis (Toona sinensis) is well known as a traditional Chinese medicine, while the underlying pharmacological mechanisms of this drug are still a matter of debate. Materials and methods: The purpose of this study was to evaluate the protective effects of non-cytotoxic concentrations of aqueous leaf extracts of Toona sinensis (TS extracts; 50-100 mu g/mL) and gallic acid (5 mu g/mL), a major component of these extracts, against AAPH-induced oxidative cell damage in human umbilical vein endothelial cells (ECs). Results: Exposure of ECs to AAPH (15 mM) decreased cell viability from 100% to 43%. However, ECs were pre-incubated with TS extracts prior to AAPH induction resulted in increased resistance to oxidative stress and cell viability in a dose-dependent manner. An increase in ECs-derived PGI(2) and IL-1 beta in response to AAPH exposure was positively correlated with cytotoxicity and negatively with IS extracts concentrations. In addition, gallic acid also suppressed PGI(2) and IL-1 beta production in AAPH-induced ECs. Notably, TS extracts/gallic acid treatment significantly inhibited ROS generation, MDA formation, SOD/catalase activity, and Bax/Bcl-2 dysregulation in AAPH-stimulated ECs. Pretreatment of ECs with TS extracts/gallic acid also suppressed AAPH-induced cell surface expression and secretion of VCAM-1, ICAM-1 and E-selectin, which was associated with abridged adhesion of U937 leukocytes to ECs. Moreover, TS extracts/gallic acid treatment significantly inhibited the AAPH-mediated up regulation of PAI-1 and down regulation of t-PA in ECs, which may decrease fibrinolytic activity. Conclusions: Therefore, Toona sinensis may possess antioxidant properties that protect endothelial cells from oxidative stress. Our results also support the traditional use of Toona sinensis in the treatment of free radical-related diseases and atherosclerosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.