甘草查尔酮 B 在体外的渗透和代谢研究
In vitro investigation of permeability and metabolism of licoricidin.
机构信息
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100000, China.
出版信息
Life Sci. 2019 Oct 1;234:116770. doi: 10.1016/j.lfs.2019.116770. Epub 2019 Aug 14.
UNLABELLED
Aim Licoricidin has multiple pharmacological activities. The present study was designed to investigate the permeability and pharmacokinetic behavior of licoricidin using in vitro models.
MATERIAL AND METHODS
First, human liver microsomes and recombinant human supersomes were used to investigate the interactions between metabolic enzymes and licoricidin. In addition, rat, minipig, rabbit, dog, monkey, and human liver microsomes were used to determine metabolic differences among species. The parallel artificial membrane permeability assay (PAMPA) was used to explore licoricidin permeability behavior.
KEY FINDINGS
At 100 μM, licoricidin strongly inhibited CYP2C9, CYP2C19, CYP3A4, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17. Licoricidin metabolism exhibited considerable differences among species; dog, pig, and rat liver microsomes showed higher metabolic capacity than the other species. Seven licoricidin metabolites were identified by liquid chromatography-tandem mass spectrometry, and hydration and hydroxylation were the major metabolic pathways. The PAMPA permeability of licoricidin was moderate at both pH 4.0 and 7.4.
SIGNIFICANCE
The present study will support further pharmacological or toxicological research on licoricidin.
目的
甘草查尔酮 A 具有多种药理活性。本研究旨在通过体外模型研究甘草查尔酮 A 的通透性和药代动力学行为。
材料和方法
首先，用人肝微粒体和重组人超微粒体研究代谢酶与甘草查尔酮 A 之间的相互作用。此外，还使用大鼠、小型猪、兔、犬、猴和人肝微粒体来确定种间代谢差异。采用平行人工膜渗透测定法（PAMPA）来探讨甘草查尔酮 A 的渗透行为。
主要发现
在 100μM 时，甘草查尔酮 A 强烈抑制 CYP2C9、CYP2C19、CYP3A4、UGT1A3、UGT1A6、UGT1A7、UGT1A8、UGT1A9、UGT2B4、UGT2B7、UGT2B15 和 UGT2B17。甘草查尔酮 A 的代谢在种间存在显著差异；狗、猪和大鼠肝微粒体显示出比其他物种更高的代谢能力。通过液相色谱-串联质谱法鉴定了 7 种甘草查尔酮 A 的代谢产物，水合和羟化是主要的代谢途径。甘草查尔酮 A 在 pH 值为 4.0 和 7.4 时的 PAMPA 通透性均为中等。
意义
本研究将为甘草查尔酮 A 的进一步药理学或毒理学研究提供支持。
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