Antimetastatic Efficacy of Orally Administered Ginsenoside Rb₁ in Dependence on Intestinal Bacterial Hydrolyzing Potential and Significance of Treatment with an Active Bacterial Metabolite

Abstract

The antimetastatic effects of orally administered ginsenoside Rb₁ (Rb₁) and an active metabolite by intestinal bacteria, 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (I), were studied, by using a spontaneous metastasis model produced by subcutaneous injection of Lewis lung carcinoma (LLC) in syngeneic C57BL/6 mice. A thorough analysis of the hydrolyzing potential (transformation by intestinal bacteria) was first done and the data found were positively correlated to the antimetastatic effect of Rb₁, through the medium of I. The transformation rate by 41% fecal specimens was less than 10% and consecutive Ginseng administrations were ineffective for the mice with hydrolyzing potential of less than 10%, which limited the antimetastatic efficacy of Rb₁. In contrast, the efficacy of I was greater than that of Rb₁, and at least comparable to that of 5-FU. No effect of I on the primary tumor growth was found, indicating a specific antimetastatic activity. In a leg amputation model with the LLC-line, an effect on survival time of I (8 mg/kg/day) equal to that of 5-FU (10 mg/kg/day) was seen and 38% mice were cured as compared with 13% cured by amputation alone. These findings suggest that the active drug is the bacterial metabolite I which should be administered rather than Rb₁.

Key words

Panax ginseng - Araliaceae - ginsenoside Rb₁ - intestinal bacterial metabolite - Lewis lung carcinoma - metastasis