The choleretic mechanism of coumarin compounds and phenolic compounds

Abstract

In this work, the choleretic properties and mechanism of coumarin compounds and phenolic compounds were studied by examining their effects on parameters such as bile flow, bile acids, electrolytes, and biliary metabolites. Choleretic intensity and property of each sample was far different. The choleretic efficacy of 6, 7-dimethylesculetin (6, 7-DME) was far weaker than that of 4-methylumbelliferone (4-MU). 4-Hydroxybenzyl alcohol (4-HBA), isoeugenol, vanillin, paeonol, and phenolphthalein accelerated bile secretion, but 4 (β-D-glucopyranosyloxy)-benzyl alcohol, safrole, and arbutin did not. 4-MU and 4-HBA underwent conjugation in the liver to give mainly a glucuronide and their metabolites were rapidly excreted into bile, but 6, 7-DME was converted into some metabolites which were excreted little by little over a long period of time. The biliary gap between cations (Na+, K+) and anions (Cl−, HCO3−, bile acids) produced after intravenous administration of 4-MU, 6, 7-DME, and 4-HBA was substantially offset by biliary concentrations of their metabolites. It was suggested that a hydroxyl group which can be mainly converted into a glucuronide is necessary in exerting a strong choleretic action. The choleretic mechanism of coumarin compounds and phenolic compounds is considered to be as follows: Their metabolites (mainly glucuronide) are actively secreted into the biliary tree as an organic anion coupled with Na+ or K+, and water is passively excreted. © 1981, The Pharmaceutical Society of Japan. All rights reserved.