PROTECTION OF RAT-LIVER MICROSOMES AGAINST CARBON TETRACHLORIDE-INDUCED LIPID-PEROXIDATION BY RED GINSENG SAPONIN THROUGH CYTOCHROME-P450 INHIBITION

A possible role of cytochrome P450 (P450) inhibition by red ginseng sa ponins in carbon tetrachloride (CCI4)-induced lipid peroxidation was i nvestigated in liver microsomes prepared from male Sprague Dawley rats . The total saponin of red ginseng standardized on ginsenosides-Rbl, - Rb2, -Rc, -Rd, -Re, and -Rg1 whose composition was studied in our prev ious report was used in the present study. The standardized saponin of red ginseng showed inhibitory effects on P450-associated monooxygenas e activities in a dose-dependent manner, particularly p-nitrophenol hy droxylase activity which has been known to represent CCl4-activating P 450 2E1 enzyme. Meanwhile, silymarin enhanced the activity of P450 2E1 enzyme in liver microsomes. When the lipid peroxidation was induced b y incubating rat liver microsomes with CCI4 in the presence of NADPH, the standardized saponin significantly blocked the formation of thioba rbituric acid-reactive substances at the same concentrations showing P 450 inhibition in liver microsomes. Silymarin revealed more potent pro tection against CCI4-induced lipid peroxidation. When the lipid peroxi dation was induced by FeCl3, in which metabolic activation may not be required, only silymarin could protect the lipid peroxidation in liver microsomes. Taken together, our present results indicated that the in hibitory effects of red ginseng saponin on P450 enzymes may have a cri tical role in CCl4-induced lipid peroxidation in rat liver microsomes and that the mechanism of hepatoprotection by red ginseng saponin may be distinct from that of silymarin.