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

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. 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 μg/mL) and gallic acid (5 μg/mL), a major component of these extracts, against AAPH-induced oxidative cell damage in human umbilical vein endothelial cells (ECs). 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 PGI2 and IL-1β in response to AAPH exposure was positively correlated with cytotoxicity and negatively with TS extracts concentrations. In addition, gallic acid also suppressed PGI2 and IL-1β 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. 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.