四君子汤非多糖功效组分的体外人源肠、肝微粒体代谢研究  

In vitro metabolism of non-polysaccharide components in Sijunzi Decoction by human intestinal and liver microsomes

作　　者：沈怡 马萍 董邦健 彭崇胜[1] 李晓波[1] SHEN Yi;MA Ping;DONG Bang-jian;PENG Chong-sheng;LI Xiao-bo(School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China)

机构地区：[1]上海交通大学药学院,上海200240

出　　处：《中草药》2023年第15期4905-4919,共15页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81973441)。

摘　　要：目的对四君子汤非多糖组分的主要活性成分进行人源肠、肝微粒体中的代谢过程研究,明确其在肠、肝中的代谢轮廓及代谢差异,为其临床应用提供科学证据。方法应用Acquity UPLC I-class/VION IMS QTOF技术分析四君子汤非多糖组分中主要活性成分(异甘草苷、甘草素、甘草酸、甘草次酸、人参皂苷Rb_(1)、人参皂苷CK、白术内酯Ⅲ)在人源肠、肝微粒体孵育体系下的代谢产物以及代谢转化途径。结果甘草酸、甘草次酸在人源肠、肝微粒体中均以Ⅰ相代谢为主;而甘草素、异甘草苷、人参皂苷Rb_(1)、人参皂苷CK则以肠Ⅱ相代谢为主。白术内酯Ⅲ在肠、肝微粒体中代谢均不显著,而四君子汤非多糖功效组分中其他化合物在肠微粒体中代谢速度均比在肝微粒体中更快。此外,甘草皂苷、人参皂苷主要进行脱糖基反应;异甘草苷以脱糖、羟基化等反应为主;甘草素则以葡萄糖醛酸结合为主;白术内酯Ⅲ则主要发生水解、羟基化反应。结论阐明了四君子汤非多糖组分中主要活性成分在人体肠道及肝脏中的代谢轮廓及代谢差异,为后续进行四君子汤非多糖功效组分的药效研究提供了数据支持,也为中药复方的功效组分研究提供了思路和策略。Objective To study the metabolism of non-polysaccharide components of Sijunzi Decoction(四君子汤)in human intestinal and liver microsomes,clarify their metabolic profiles and metabolic differences,and provide support for their clinical application.Methods Acquity UPLC I-class/VION IMS QTOF was applied to analyze the metabolites and metabolic transformation of non-polysaccharide components(isoliquiritin,liquiritigenin,glycyrrhizic acid,glycyrrhetinic acid,ginsenoside Rb1,ginsenoside CK,atractylenolide Ⅲ)of Sijunzi Decoction in human intestinal and liver microsomes.Results Glycyrrhizic acid and glycyrrhetinic acid were mainly metabolized by phase Ⅰ in human intestinal and liver microsomes,while isoliquiritin,liquiritigenin,ginsenoside Rb1,and ginsenoside CK were mainly metabolized by phase Ⅱ in human intestinal microsomes.Atractylenolide Ⅲ was less metabolized in both intestinal and liver microsomes,while other compounds in the non-polysaccharide components of Sijunzi Decoction were metabolized more rapidly in human intestinal microsomes than in liver microsomes.Glycyrrhizic acid and ginsenoside mainly underwent deglycosylation.Isoliquiritin mainly underwent deglycosylation and hydroxylation.Liquiritigenin mainly took combination reaction with glucuronic acid.Atractylenolide Ⅲ mainly underwent hydrolysis and hydroxylation.Conclusion This study elucidates the metabolic profiles and metabolic differences of the non-polysaccharide components of Sijunzi Decoction in human intestinal and liver microsomes,which is important for clarifying the metabolic transformation process of Sijunzi Decoction in the body,and also provides ideas and strategies for traditional Chinese medicine prescriptions.

关 键 词：四君子汤 人源肠微粒体 人源肝微粒体 体外代谢 异甘草苷 甘草素 甘草酸 甘草次酸 人参皂苷Rb_(1) 人参皂苷CK 白术内酯Ⅲ 

分 类 号：R285.61[医药卫生—中药学]