PHARMACOLOGICAL STUDIES ON IRIDOID COMPOUNDS. III. THE CHOLERETIC MECHANISM OF IRIDOID COMPOUNDS

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We made a study on choleretic property and mechanism of action of iridoid compounds as well as dehydrocholate (DHC), cholate (CA), and salicylate (SA), examining their effects on factors such as bile flow, bile acids, electrolytes (Na^+, K^+, Cl^-, and HCO_3^-), and their metabolites. Each sample showed a characteristic property, respectively. Genipin and patrinoside decreased biliary concentrations of bile acids, Na^+, Cl^-, and HCO_3^-, corresponding to their rapid choleretic actions which were due to bile acidsindependent fraction. The choleretic action of DHC is approximately twice as potent as that of CA. Their actions were due to bile acids-dependent fraction. CA gave a marked increase in Na^+ concentration but DHC did not. And both compounds gave a marked diminution in Cl^- concentration and weakly decreased HCO_3^- concentration. SA showed a weak and durable choleretic action and also gave a marked increase in HCO_3^- concentration. The main metabolite detected from the bile given genipin was genipin-1-O-glucuronic acid (GGA). The periodical pattern of GGA level in bile was in agreement with that of genipininduced choleretic action, and quantitatively cation-anion gap produced was nearly compensated by biliary concentration of GGA. From our various results, the choleretic mechanism of iridoid compounds is considered to be as follows : The hemiacetal moiety of them undergoes conjugation in the liver to give glucuronide. Glucuronide thus formed is secreted into the biliary tree being coupled mainly with Na^+ and water is passively excreted.
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PHARMACOLOGICAL STUDIES ON IRIDOID COMPOUNDS. III. THE CHOLERETIC MECHANISM OF IRIDOID COMPOUNDS

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