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To evaluate the hepatoprotective effect of Red Ginseng (RG), we isolated a main constituent 20(S)-ginsenoside Rg3 from RG, and its metabolite 20(S)-ginsenoside Rh2 by human intestinal microflora, and investigated their hepatoprotective activities in tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity of HepG2 cells and mice. When HepG2 cells were treated with t-BHP, its cytotoxicity was significantly increased. 20(S)-Ginsenoside Rh2 potently protected its cytotoxicity, but 20(S)-ginsenoside Rg3 weakly protected it. Intraperitoneally and orally administered 20(S)-ginsenoside Rh2 to t-BHP-injured mice significantly inhibited the increase of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Orally administered 20(S)-ginsenoside Rg3 also showed the inhibition against the increase of ALT and AST of t-BHP-induced mice. However, intraperitoneally administered 20(S)-ginsenoside Rg3 could not inhibit the elevation of serum ALT and AST activities. These results suggest that 20(S)-ginsenoside Rg3 a main component of RG may be a prodrug for hepatotoxicity.
Lee et al. (Sat,) studied this question.