Antimutagenicity of Japanese traditional herbs, gennoshoko, yomogi, senburi and iwa-tobacco.

The multistage induction theory is generally regarded as the mechanism of carcinogenesis. In order to prevent the initiation stage of carcinogenesis, it is meaningful to discover the functional components of edible plants. The objective of this research was to test the antimutagenicity of the functional components of several typical traditional herbs used in Japan. The traditional herbs, gennoshoko (Geranium nepalense var. thunbergii), yomogi (Artemisia vulgaris var. indica), senburi (Swertia japonica), iwa-tobacco (Conandron ramondioides), sarunokoshikake (Elfvingia applanata), kanzo (Glycyeehiza uralensis Fisch) and matatabi (Actinidia polygama) were examined by Ames mutagenesis assay test with Salmonella typhimurium TA98 and TA100 against mutagens, Trp-P-1, Trp-P-2 and B(a)P. The water-soluble components or volatile oil of the herbs were extracted in boiling water. The extracts of gennoshoko showed strong antimutagenicity against B(a)P with S. typhimurium TA98 and TA100, as well as Trp-P-1 and Trp-P-2 with S. typhimurium TA98. Yomogi, senburi and iwa-tobacco were also proved to have good antimutagenicity against Trp-P-1 and Trp-P-2 with S. typhimurium TA98, but weaker antimutagenicity against B(a)P. Other herbs did not show any obvious antimutagenicity against these mutagens. In addition, the volatile oil of yomogi also had remarkable antimutagenic effect against the mutagens we used with S. typhimurium TA98.

Metabolism of [6,7-3H, 35S] estradiol 17-sulfate in rats.

To confirm whether or not the sulfo group of estradiol 17-sulfate (ES) is removed during in vivo metabolism in rats, the doubly labeled conjugate [6,7-3H, 35S] ES was injected into rats, and its biliary and urinary metabolites were determined by reverse isotope dilution method (RIDM). In male rats, the major radioactivity was detected in biliary disulfate fraction, which was composed of mainly ES and its two minor metabolites, 2-hydroxyestradiol 17-sulfate (2-OH-ES) and 2-methoxyestradiol 17-sulfate (2-MeO-ES). In female rats, in contrast, the radioactivity was dispersed into three fractions:biliary monosulfate, biliary disulfate, and urinary monosulfate fractions (Frs.) In both monosulfate Frs., 7beta-hydroxyestradiol 17-sulfate was detected as the major metabolite followed by 6alpha-, 6beta-, and 15beta-hydroxyestradiol 17-sulfates. Like male rats, 2-OH-ES and 2-Meo-ES as the minor products were detected in biliary disulfate fraction. The isotope ratios of ES and its metabolites in both sexes were essentially the same as that of the dose except that of 6alpha-hydroxylated metabolite, which may be derived from the loss of the tritium labeled at C6. These results confirm the occurrence of the direct metabolism of ES in rats.

On the structures of hydroxylated metabolites of estradiol 17-sulfate by rat liver microsomes.

The metabolism of estradiol 17-sulfate (ES) by hepatic microsomes of female rats produced four new metabolites in addition to 2- and 4-hydroxyestradiol 17-sulfates (2- and 4-OH-ES), which were detected on an HPLC chromatogram. By comparison with synthetic specimens, three of these compounds were identified as 6alpha-, 6beta-, and 7beta-hydroxyestradiol 17-sulfates. To elucidate the structure of the remaining metabolite, a large-scale incubation of ES was carried out, followed by isolation using preparative HPLC to give the single material, which was assigned as 15beta-hydroxyestradiol 17-sulfate by instrumental analyses. On the other hand, when ES was incubated with the microsomes of male rats, 2-OH-ES was produced accompanied by two minor products: 4-OH-ES and a metabolite of unknown structure. The results show clearly that the metabolism of ES by rat hepatic microsomes is remarkably different between the sexes.