Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite

Author(s): Hasegawa H, Uchiyama M


The antimetastatic effects of orally administered ginsenoside Rb1 (Rb1) and an active metabolite by intestinal bacteria, 20-O-beta-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 S-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.

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