基于超高效液相色谱-质谱联用技术的人参皂苷体外Ⅰ相代谢研究

发布时间：2018-08-20 14:02

【摘要】：口服药物必须经过胃肠道的吸收代谢等过程才能进入体内发挥疗效,但是药物体内代谢的复杂性使其研究相对困难。因此,建立药物的体外代谢模型研究其代谢产物及代谢规律是简单且必要的实验手段。本研究采用离体肠道菌厌氧培养法对人参皂苷提取物进行体外培养,利用超高效液相色谱-质谱联用法(UPLC/MS)检测分析肠内菌代谢产物。通过比较代谢前后的化学指纹图,共检测到25种三醇型、15种二醇型人参皂苷体外肠内菌代谢物和1种齐墩果酸型体外肠内菌代谢物,这些代谢物主要通过去糖基作用产生,同时包括部分氧化还原反应。实验进一步对人参皂苷的主要肠内菌代谢物(包括Rh_1、Rh_2、Compound K、F1)进行体外肝细胞色素P450酶(CYP450)代谢研究,均检测到氧化还原反应代谢产物。结果表明,人参皂苷类成分在肠道菌群作用下主要产生去糖基化产物,而在CYP450作用下主要产生羟基化等氧化还原反应产物。该结果可为人参皂苷类成分的体内代谢研究提供重要参考。
[Abstract]:Oral drugs must go through the process of gastrointestinal absorption and metabolism in order to enter the body to play a therapeutic effect, but the complexity of drug metabolism in vivo makes it relatively difficult to study. Therefore, it is a simple and necessary experimental method to establish drug metabolism model in vitro to study its metabolites and metabolic laws. In this study, ginsenoside extracts were cultured in vitro by anaerobic culture of isolated intestinal bacteria, and the metabolites of intestinal bacteria were detected and analyzed by ultra-high performance liquid chromatography-mass spectrometry (UPLC/MS). By comparing the chemical fingerprinting before and after metabolism, a total of 25 triol type ginsenoside metabolites and 1 oleanolic acid type intestinal bacteria metabolites were detected in vitro. These metabolites were mainly produced by deglycosylation. It also includes partial redox reactions. The main metabolites of ginsenoside in intestinal bacteria (including Rh _ 1 Rh _ 2H _ 2Compound KF _ 1) were further studied on the metabolism of hepatocyte cytochrome P450 enzyme (CYP450) in vitro. All the metabolites of redox reaction were detected. The results showed that ginsenosides mainly produced deglycosylation products under the action of intestinal flora, while hydroxylation and other redox products were mainly produced under the action of CYP450. The results can provide an important reference for the study of ginsenosides metabolism in vivo.
【作者单位】：中国科学院长春应用化学研究所;中国科学技术大学;
【基金】：国家自然科学基金重点项目(81530094);国家自然科学基金面上项目(81573574、81473537)资助
【分类号】：O657.63;R965

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