|
Glycosides of herbal medicines, such as glycyrrhizin, ginsenosides, kalopanaxsaponins, rutin and ponicirin, were studied regrading their metabolic fates and pharmacological actions in relation to intestinal bacterial using germ-free, gnotobiotic and conventional animals. When glycyrrhizin (GL) was orally administered, 18β-glycyrrhetinic acid (GA), not GL, was detected in plasma and intestinal contents of gnotobiotic and conventional rats. However, GA could not be detected in germ-free rats. When GL incubated with human intestinal bacteria, it was directly metabolized to GA (＞95%) or via 18 β-glycrrhetinic acid-3- β-D-glucuronide (＜5%). Orally administered GL was effective in gnotobiotic and conventional rats for liver injury induced by carbon tetrachloride, but was not effective in germ-free rats. When ginseng saponins were orally administered to human beings, compound K was active for tumor metastasis and allergy. When kalopanaxsaponins were incubated with human intestinal microflora, they were metabolized to kalopanaxsaponin, A, kalopanaxsaponin I and hederagenin. These metabolites were active for rheumatoid arthritis and diabetic mellitus while the other kalopanxsaponins were not. When flavonoid glycosides were orally administered to animals, aglycones and/or phenolic acids were detected in the urine. The metabolic pathways proceeded by intestinal bacteria rather than by liver or blood enzymes. These metabolites were active for rheumatoid arthritis and diabetic mellitus while the other kalopanxsaponins were not. When flavonoid glycosides were orally administered to animals, aglycones and/or phenolic acids were detected in the urine. The metabolic pathways proceeded by intestinal bacteria rather than by liver or blood enzymes. These metabolites, aglycones and phenolic acids, showed antitumor, antiinflammatory and antiplatelet aggregation activities. These findings suggest that glycosides of herbal medicines are prodrugs.
|