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吉林化工学院学报, 2025, 42(1): 11-22     https://doi.org/10.16039/j.cnki.cn22-1249.2025.01.003
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龙胆泻肝汤的体外肝微粒体代谢研究
张冉冉1,张艳2*,杨秀东1*
(1.吉林化工学院 化学与制药工程学院,吉林 吉林132022;2.嘉兴大学 医学院,浙江 嘉兴 314001)
Study on Liver Microsomal Metabolism in Vitro of Longdan Xiegan Decoction
ZHANG Ranran1,ZHANG Yan2*,YANG Xiudong1*
(1.School of Chemical and Pharmaceutical Engineering, Jilin University of Chemical Technology, Jilin City 132000, China:2.School of Medicine ,Jiaxing University,Jiaxing 314001 .China)
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摘要 探究龙胆泻肝汤中药物成分在体外肝微粒体代谢模型中的转化情况。首先,利用龙胆、黄苓、栀子、地黄、泽泻、车前子、当归、川木通、柴胡和甘草进行药物制备,并通过煎制、冷却、复煎、浓缩、真空干燥等步骤得到龙胆泻肝汤粉末。其次,利用大鼠肝组织制备肝微粒体,包括肝脏灌洗、离心、过滤、沉淀等步骤,最终得到含有 20%甘油的肝微粒体酶。而后,构建体外肝微粒体酶孵育体系,在150μL的反应体系中加人微粒体蛋白、NADPH、氯化镁和底物,在不同时间节点下进行采样操作,并对样品分别进行HPLC和 MS分析。HPLC结果显示,随着孵育时间的延长,部分药物成分发生转化,推测可能形成新的代谢产物。MS分析鉴定出龙胆苦苷、京尼平苷、京尼平苷酸,黄芩苷,柴胡皂苷A和柴胡皂苷D等原型物质,并推测出黄芩苷可能发生的代谢途径。综上所述,构建了体外肝微粒体代谢模型,结合HPLC-MS技术,对龙胆泻肝汤的肝微粒体的代谢过程进行了初步模拟和研究,为进一步探究其药效机制提供了参考。
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张冉冉
张艳
杨秀东
关键词:  龙胆泻肝汤   肝微粒体   毒性机制    
Abstract: The aim was to investigate the transformation of drug components in Longdan Xiegan Decoction in liver microsomal metabolism model in vitro. Firstly, Gentiana manshurica Kitag, Bupleurum chinense DC, Scutellaria baicalensis Georgi, Gardenia jasminoides Ellis, Rehmannia glutinosa Libosch, Alisma orientale, Plantago asiatica L, Angelica sinensis (Oliv.) Diels, Aristolochia manshuriensis Kom and Glycyrrhiza uralensis Fisch were used to prepare the decoction, and the decoction was prepared by decocting, cooling, decocting, concentrating and vacuum drying. Secondly, liver microsomes were prepared from rat liver tissues, including liver lavage, centrifugation, filtration and precipitation, and finally liver microsomal enzymes containing 20% glycerol were obtained. Then, an in vitro liver microsomal enzyme incubation system was constructed, and microsomal protein, NADPH, magnesium chloride and substrate were added into the reaction system of 150 μL. Sampling operations were performed at different time nodes, and the samples were analyzed by HPLC and MS, respectively. HPLC results showed that with the extension of incubation time, some drug components were transformed and new metabolites may be formed. Gentiopicroside, geniposide, geniposide acid, baicalin, saikosaponin A and saikosaponin D were identified by MS analysis, and the possible metabolic pathway of baicalin was speculated. In summary, this study established in vitro liver microsomal metabolic model, combined with HPLC - MS technology, preliminatively simulated and studied the metabolic process of liver microsomes in Longdan Xiegan Decoction, and provided a reference for further exploration of its pharmacodynamic mechanism.
Key words:  Longdan Xiegan Decoction     liver microsome    toxicity mechanism
               出版日期:  2025-01-25      发布日期:  2025-07-05      整期出版日期:  2025-01-25
ZTFLH:  R 575.5  
引用本文:    
张冉冉, 张艳, 杨秀东. 龙胆泻肝汤的体外肝微粒体代谢研究[J]. 吉林化工学院学报, 2025, 42(1): 11-22.
ZHANG Ranran, ZHANG Yan, YANG Xiudong. Study on Liver Microsomal Metabolism in Vitro of Longdan Xiegan Decoction. Journal of Jilin Institute of Chemical Technology, 2025, 42(1): 11-22.
链接本文:  
https://xuebao.jlict.edu.cn/CN/10.16039/j.cnki.cn22-1249.2025.01.003  或          https://xuebao.jlict.edu.cn/CN/Y2025/V42/I1/11
[1] 张冉冉, 张艳, 杨秀东. 基于网络药理学的龙胆泻肝汤肝毒性机制研究[J]. 吉林化工学院学报, 2024, 41(11): 7-11.
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