title: Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Wei-Man
authors.initials: WM
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ze-Yu
authors.initials: ZY
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China. Electronic address: liulee@yeah.net.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, China. Electronic address: xdliu@cpu.edu.cn.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004347:Drug Interactions; D006034:Glycyrrhetinic Acid / Q000097:blood*; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007795:Laminaria; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid
keywords: Glycyrrhetinic acid; Glycyrrhizic acid; In situ single-pass intestinal perfusion; Intestinal contents; Laminaria japonica; Liquorice; Pharmacokinetics