Smilax china Root Extract Detoxifies Nicotine by Reducing Reactive Oxygen Species and Inducing CYP2A6

Abstract

Resveratrol has a beneficial effect of lowering reactive oxygen species (ROS) and reduces cellular oxidative stress. We hypothesized that ethanol extract of Smilax china root (EESC) rich in resveratrol (RES) and oxyresveratrol (OXY) could reduce ROS caused by nicotine and promoting nicotine turnover by induction of CYP2A6. The amount of cotinine converted from nicotine was quantified by the direct barbiturate assay method. Expression of CYP2A6 was unregulated by RES, OXY, or EESC, respectively. Pretreatment of RES (50, 100, and 250 mu M), OXY (50, 100, and 250 mu M), and RES+OXY (50 and 100 mu M) inhibited cytotoxicity and ROS production caused by nicotine in a dose-dependent manner. EESC pretreatment (1.8 mg/mL) increased cell viability by 1.5-fold higher than the control (nicotine only), and lowered cellular ROS levels. A significant amount of the conversion of nicotine to cotinine was observed in EESC pretreatment by CYP2A6 induction in HepG2 cells. These results suggested that hepatic induction of CYP2A6 and ROS reduction by EESC activate nicotine metabolism and reduce cellular oxidative stress.