Relation of Intestinal Bacteria to Pharmacological Effects of Glycosides

Abstract

Popular natural glycosides such as glycyrrhizin (GL, licorice), barbaloin (aloe) and baicalin (BG, Scutellaria baicalensis) were studied regarding their metabolic fates and actions in relation to intestinal bacteia by using germ-free and gnotobiote rats. When GL was administered orally, the aglycone, glycyrrhetic acid (GA), was not detected in the plasma or intestinal contents of germ-free rats, but was detected in considerable amounts in the plasma and intestinal contents of conventional and gnotobiote rats, associated with the human intestinal bacterium Eubacterium sp. strain GLH capable of hydrolyzing GL to GA. GL was not detected in the plasma of the three groups of rats after oral administration. GL was effective in the conventional and gnotobiote rats with liver injury caused experimentally by carbon tetrachloride, but not in germfree rats with liver injury. These results indicate that orally administered GL is a prodrug and activated to GA by intestinal bacteria. Barbaloin, a laxative, was ineffective in conventional rats, but showed strong purgative action to gnotobiote rats associated with the human intestinal bacterium Eubacterium sp. strain BAR, which is capable of transforming barbaloin to aloe-emodin anthrone. Barbaloin is also a prodrug and activated to aloe-emodin anthrone by human intestinal bacteria. Animal differences in the laxative effect of barbaloin are due to species differences in intestinal bacteria. When BG was administered orally to conventional rats, BG, but not the aglycone baicalein (B), was found in the plasma. However, when BG was administered to germ-free rats, both BG and B were hardly detected in the plasma. Even after oral administration of B, BG was detected, but not B. These findings suggest that BG is a prodrug hydrolyzed to B by intestinal bacteria, and then conjugated to BG from the absorbed B in the body.