EXPRESSION OF THE ANTIMETASTATIC EFFECT INDUCED BY JUZEN-TAIHO-TO IS BASED ON THE CONTENT OF SHIMOTSU-TO CONSTITUENTS

We investigated the inhibitory effect of oral administration of Juzen- taiho-to, a Kampo Japanese herbal medicine, and its related formulatio ns on the experimental liver and lung metastasis of tumor cells in viv o. Oral administration of Juzen-taiho-to for 7d before tumor inoculati on significantly reduced the number of liver metastatic colonies of co lon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral adminis tration for this same period before tumor inoculation also significant ly inhibited lung metastasis of B16-BL6 melanoma cells, Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Sh ikunshi-to prescriptions together with two crude drugs (Cinnamomi Cort ex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a signifi cant reduction in the number of metastatic felonies and the liver weig ht as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect, Unsei-in containing four Shimotsu-to consti tuents was also active in inhibiting liver metastasis. Toki-shakuyaku- san and Ninjin-yoei-to, which include all Shimotsu-to constituents exc ept Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, w hich contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably thr ough an inhibitory mechanism different from Juzen-taiho-to. These resu lts suggest that the anti-metastatic effect of Juzen-taiho-to is partl y associated with its Shimotsu-to-derived constituents.