Akao T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Biol Pharm Bull. 1999 Aug;22(8):787-93. doi: 10.1248/bpb.22.787.
Ruminococcus sp. PO1-3, an intestinal bacterium isolated from human feces, metabolized glycyrrhizin (GL) to glycyrrhetic acid (GA) and GA to 3-oxo-glycyrrhetic acid (3-oxo-GA) and possessed GL beta-D-glucuronidase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) involved in the metabolism of GL. This bacterial growth was enhanced by GL at a concentration of 0.4 mm and was suppressed by GA at concentration of 1.0 mM. Chenodeoxycholic acid, deoxycholic acid and lithocholic acid among the bile acids added to this bacterium suppressed the growth and GL beta-D-glucuronidase activity and 3beta-HSD activity incident to it at a concentration of 1.0 mM, while cholic acid, hyodeoxycholic acid and glycine and taurin conjugates of cholic acid, chenodeoxycholic acid, deoxycholic acid and lithocholic acid had almost no effect on this bacterium at a concentration of 0.2 to 1.0 mm. However, these enzyme activities of this sonicated bacteria were inhibited by all of these bile acids. Although each bile acid and GL added to bacteria at the same time suppressed the growth and the amount of metabolite GA by all bile acids used except cholic acid, taurocholic acid and taurodeoxycholic acid with GL, a combination of each bile acid and GA eased the growth inhibition caused by GA at a concentration of 0.2 mM and enhanced the amount of metabolite 3-oxo-GA by the glycine conjugate of bile acids with GA. GL or GA added after 6 h culture with each of these bile acids and bacteria was metabolized to a relatively large amount of GA by chenodeoxycholic acid and lithocholic acid and their glycine and taurine conjugates, glycocholic acid and taurodeoxycholic acid, or had almost no effect on the amount of metabolite 3-oxo-GA, respectively. These results showed that although GL added after the exposure to bile acid and GA and bile acid added at the same time as bacteria had different bile acid action, these conditions enhanced the amount of metabolite GA from GL and metabolite 3-oxo-GA from GA.
从人粪便中分离出的肠道细菌瘤胃球菌属PO1-3,可将甘草甜素(GL)代谢为甘草次酸(GA),并将GA代谢为3-氧代甘草次酸(3-氧代-GA),且拥有参与GL代谢的GLβ-D-葡萄糖醛酸酶和3β-羟基类固醇脱氢酶(3β-HSD)。该细菌在0.4 mM浓度的GL作用下生长增强,而在1.0 mM浓度的GA作用下生长受到抑制。添加到该细菌中的胆汁酸中,鹅去氧胆酸、脱氧胆酸和石胆酸在1.0 mM浓度时抑制其生长以及与之相关的GLβ-D-葡萄糖醛酸酶活性和3β-HSD活性,而胆酸、猪去氧胆酸以及胆酸、鹅去氧胆酸、脱氧胆酸和石胆酸的甘氨酸和牛磺酸共轭物在0.2至1.0 mM浓度时对该细菌几乎没有影响。然而,这些经超声处理的细菌的这些酶活性受到所有这些胆汁酸的抑制。尽管同时添加到细菌中的每种胆汁酸和GL除了胆酸、牛磺胆酸和牛磺脱氧胆酸与GL外,均抑制了所有所用胆汁酸的生长和代谢产物GA的量,但每种胆汁酸与GA的组合在0.2 mM浓度时减轻了GA引起的生长抑制,并增加了胆汁酸与GA的甘氨酸共轭物代谢产物3-氧代-GA的量。在与这些胆汁酸和细菌一起培养6小时后添加GL或GA,鹅去氧胆酸和石胆酸及其甘氨酸和牛磺酸共轭物、甘氨胆酸和牛磺脱氧胆酸可将其代谢为相对大量的GA,或者分别对代谢产物3-氧代-GA的量几乎没有影响。这些结果表明,尽管在暴露于胆汁酸后添加GL以及与细菌同时添加胆汁酸具有不同的胆汁酸作用,但这些条件增加了GL代谢产物GA和GA代谢产物3-氧代-GA的量。