36. Novel antioxidant action of dibenzo[a,c]cyclooctadiene derivatives from Fructus Schisandrae (Wuweizi).

Kam Ming Ko and Siu Po Ip

Department of Biochemistry and Hong Kong Traditional Chinese Medicine Research Center, the Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong

Using a rodent model of carbon tetrachloride (CCl4) hepatotoxicity for measuring in vivo antioxidant activities, a lignan-enriched extract of Fructus Schisandrae was found to enhance hepatic gluthione status in rats. The beneficial effect of the lignan-enriched Fructus Schisandrae extract on hepatic glutathione status was envidenced by a generalized protection against hepatotoxicity induced by CCl4, cadmium chloride and aflatoxin b1. The mechanism of Fructus Schisandrae-induced enhancement of hepatic glutathione status possibly involves the factilitation of reduced glutathione (GSH) regeneration through the glutathione reductase-catalyzed and NADPH-mediated reaction. Pretreatment of animals with the lignan-enriched extract of Fructus Schisandrae was also found to protect against free radical-induced tissue damage in the heart and skeletal muscle. Activity-directed fractionation of lignan-enriched extract resulted in the isolation of schisandrin B, a dibenzo[a,c] cyclooctadiene derivative, which was found to enhance the functioning of the glutathione antioxidant/detoxification system in mouse liver. The crucial antioxidant action of schisandrin B is likely mediated by enhancing the mitochrondrial glutathion redox status. Preliminary structure-activity-relationship studies indicated that the methylenedioxy group of the liqnoid molecule may be an important structural determinant for enhancing the hepatic mitochrondrial GSH level. The ability of Fructus Schisandrae derived lignans to produce a sustainable and GSH-mediated antioxidant effect on various tissues suggests their use for the prevention of free radical-mediated disease.

Keywords: Schisandra chinensis; glutathione; antioxidant; mitochondria; heart; liver