A Comparison of the Antihepatotoxic Activity between Glycyrrhizin and Glycyrrhetinic Acid

Abstract

A comparison of antihepatotoxic activities between glycyrrhizin (18β-GL) and its genuine aglycone, glycyrrhetinic acid (18β-GA), was carried out using in vivo and in vitro assay methods. The oral administration of 18β-GA at 1, 24, and 48 h before D-galactosamine (GalN) treatment significantly reduced the increase of serum transaminase activities 24 h after GalN treatment, whereas 18β-GL did not inhibit the increase of serum transaminase activities. The intraperitoneal administration of 18β-GA 1 h before GalN treatment restored the increase of serum transaminase activities with lower doses than 18β-GL. In CCl₄-induced cytotoxicity of primary cultured rat hepatocytes, 18β-GA protected the CCl₄-induced leakage of transaminase at doses of 5 to 50 µg/ ml, whereas 18β-GL inhibited slightly the leakage at a dose of 1000 µ/ml. In the same way, 18α-GA, the a-isomer of 18β-GA, reduced the CCl₄-induced cytotoxicity more strongly than 18α-GL. Furthermore, the adsorbability of 18α,β-GA on primary cultured rat hepatocytes was higher than that of 18α,β-GL. These results suggest that 18α,β-GA is a more potent antihepatotoxic agent than 18α,β-GL, and that the potency of the antihepatotoxic compounds parallels their adsorbability in hepatocytes.

Key words

18α,β-Glycyrrhizin - 18α,β-glycyrrhetinic acid - galactosamine - carbon tetrachloride - liver injury - rat hepatocytes - adsorbability