Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats  

作　　者：ZHAO Wei-Man JIANG Shu-Wen CHEN Yang ZHONG Ze-Yu WANG Zhong-Jian ZHANG Mian LI Ying XU Ping LIU Li LIU Xiao-Dong 

机构地区：[1]State Key Laboratory of Natural Medicines,Department of Complex Prescription of TCM,China Pharmaceutical University

出　　处：《Chinese Journal of Natural Medicines》2015年第7期540-549,共10页中国天然药物（英文版）

基　　金：supported by funding from the National Basic Research Program of China(973 Program)(Nos.2011CB505300,2011CB505303)

摘　　要：The present study was designed to investigate the effects of Laminaria japonica(Laminaria) on pharmacokinetics of glycyrrhetinic acid(GA) following oral administration of Liquorice extract in rats.Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract,respectively,plasma samples were obtained at various times and the concentrations of GA,liquiritigenin,and isoliquiritigenin were measured by LC-MS.The effects of Laminaria extract on pharmacokinetics of GA were also investigated,following single-dose and multidose of glycyrrhizic acid(GL).The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model.The metabolism of GL to GA in the contents of small and large intestines was also studied.The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA,accompanied by a shorter Tmax.Similar alteration was observed following multidose administration.However,pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria.Similarly,Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed.The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum,but did not affect the intestinal absorption of GA.It was found that Laminaria enhanced the metabolism of GL to GA in large intestine.In conclusion,Laminaria increased plasma exposures of GA following oral administration of liquorice or GL,which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.The present study was designed to investigate the effects of Laminaria japonica （Laminaria） on pharmacokinetics of glycyrrhetinic acid （GA） following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid （GL）. The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter T~. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

关 键 词：PHARMACOKINETICS LIQUORICE Laminaria japonica Glycyrrhizic acid Glycyrrhetinic acid In situ single-pass intestinal perfusion Intestinal contents 

分 类 号：R969.1[医药卫生—药理学]