Transport and metabolism of flavonoids from Chinese herbal remedy Xiaochaihu-tang across human intestinal Caco-2 cell monolayers  

作　　者：Jie-yu DAI Jun-ling YANG Chuan LI 

机构地区：[1]Shanghai Center for DMPK Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2008年第9期1086-1093,共8页中国药理学报（英文版）

基　　金：Supported by the National Natural Science Foundation of China （No 30271596）, the Chinese Ministry of Science and Technology （No 2004CB518902 and 2005CB523403）, and the Science ＆ Technology Commission of Shanghai Municipality （No 01DJ19008 and 04DZ19215）. Chuan LI designed research; Jie-yu DAI and Jun-ling YANG performed research;Chuan LI, Jie-yu DAI, and Junling YANG analyzed data; Chuan LI wrote the paper.

摘　　要：Aim： To investigate the limiting factors for oral bioavailability of flavonoids derived from the Chinese herbal remedy Xiaochaihu-tang. The investigational flavonoids included baicalin, wogonoside, oroxylin-A 7-O-β-D-glucopyranosiduronide, liquiritin, liquiritin apioside, isoliquiritin, and isoliquiritin apioside, as well as their aglycones baicalein, wogonin, oroxylin-A, liquiritigenin, and isoliquiritigenin. Methods： Caco-2 cell monolayers were used and the apparent permeability both in apical to basolateral and basolateral to apical directions was measured for each investigational compound. Meanwhile, chemoinformatics was carried out to provide insight into the mechanism governing the permeability. In addition, carrier-mediated transport with or without inhibitors, as well as the metabolism by conjugation, was also examined with Ca- co-2 cell monolayers for the flavonoids. Results： The investigational flavonoid aglycones exhibited favorable membrane permeability, but efficient glucuronidation and/or sulfation by the enterocytes may limit their bioavailability. For the flavonoid glycosides, their poor membrane permeability was found to be caused by high hydrogen-bonding potential. Among the glycosides, oroxylin-A 7-O-β- D-glucopyranosiduronide, isoliquiritin, and isoliquiritin apioside were transported under the mediation of the efflux transporters multidrug resistance-associated protein and/or P-glycoprotein. Conclusion： The limiting factors of oral bioavailability for the flavonoids derived from Xiaochaihu-tang appeared to include poor membrane permeability, significant efflux, and efficient intestinal metabolism by conjugation.Aim： To investigate the limiting factors for oral bioavailability of flavonoids derived from the Chinese herbal remedy Xiaochaihu-tang. The investigational flavonoids included baicalin, wogonoside, oroxylin-A 7-O-β-D-glucopyranosiduronide, liquiritin, liquiritin apioside, isoliquiritin, and isoliquiritin apioside, as well as their aglycones baicalein, wogonin, oroxylin-A, liquiritigenin, and isoliquiritigenin. Methods： Caco-2 cell monolayers were used and the apparent permeability both in apical to basolateral and basolateral to apical directions was measured for each investigational compound. Meanwhile, chemoinformatics was carried out to provide insight into the mechanism governing the permeability. In addition, carrier-mediated transport with or without inhibitors, as well as the metabolism by conjugation, was also examined with Ca- co-2 cell monolayers for the flavonoids. Results： The investigational flavonoid aglycones exhibited favorable membrane permeability, but efficient glucuronidation and/or sulfation by the enterocytes may limit their bioavailability. For the flavonoid glycosides, their poor membrane permeability was found to be caused by high hydrogen-bonding potential. Among the glycosides, oroxylin-A 7-O-β- D-glucopyranosiduronide, isoliquiritin, and isoliquiritin apioside were transported under the mediation of the efflux transporters multidrug resistance-associated protein and/or P-glycoprotein. Conclusion： The limiting factors of oral bioavailability for the flavonoids derived from Xiaochaihu-tang appeared to include poor membrane permeability, significant efflux, and efficient intestinal metabolism by conjugation.

关 键 词：Caco-2 cell monolayer CHEMOINFORMATICS TRANSPORT EFFLUX METABOLISM flavonoid Xiaochaihu-tang. 

分 类 号：R96[医药卫生—药理学]