小檗碱及药根碱在大鼠肝微粒体中的代谢转化研究
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摘要
目的进行小檗碱和药根碱在大鼠肝微粒体中的代谢转化研究,尝试给中药有效成分的体外和体内关联研究提供一定的参考。方法制备大鼠肝微粒体,用Brad ford法测定酶活性,以此配制大鼠肝微粒体体外温孵体系,加入药物温孵,用质谱进行检测测定并比较小檗碱、药根碱代谢产物图谱。结果检测到小檗碱经大鼠肝微粒体代谢后产物中有药根碱,药根碱经大鼠肝微粒体代谢后产物中有巴马汀,但小檗碱代谢产物中未见巴马汀。结论小檗碱和药根碱是同母核生物碱,在肝微粒体中孵化可相互影响,但体外代谢无法简单关联体内代谢过程。
Objective To investigate the metabolic transformation of berberine and jatrorrhizine in rat liver microsomes, and to provide a reference for the in vitro and in vivo association studies of active constituents in traditional Chinese medicine(TCM).Methods The rat liver microsome was prepared, and the enzymatic activity was determined by Brad ford method to prepare the in vitro incubation system of rat liver microsomes. After the incubation in the presence of berberine and jatrorrhizine, mass spectrometry was used to detect and compare the metabolites of berberine and jatrorrhizine. Results After the metabolic transformation in rat liver microsomes, jatrorrhizine was one of the metabolites of berberine; palmatine was one of the metabolites of jatrorrhizine, but not of berberine. Conclusion Berberine and jatrorrhizine are from the same parent alkaloid and they can affect each other during the incubation in liver microsomes. However, the in vitro metabolism cannot be associated with the in vivo metabolism.
Objective To investigate the metabolic transformation of berberine and jatrorrhizine in rat liver microsomes, and to provide a reference for the in vitro and in vivo association studies of active constituents in traditional Chinese medicine(TCM).Methods The rat liver microsome was prepared, and the enzymatic activity was determined by Brad ford method to prepare the in vitro incubation system of rat liver microsomes. After the incubation in the presence of berberine and jatrorrhizine, mass spectrometry was used to detect and compare the metabolites of berberine and jatrorrhizine. Results After the metabolic transformation in rat liver microsomes, jatrorrhizine was one of the metabolites of berberine; palmatine was one of the metabolites of jatrorrhizine, but not of berberine. Conclusion Berberine and jatrorrhizine are from the same parent alkaloid and they can affect each other during the incubation in liver microsomes. However, the in vitro metabolism cannot be associated with the in vivo metabolism.
引文
[1]杨岩涛,陶叶琴,唐闻汉,等.中药控缓释制剂多成分整体受控的超分子机制探讨[J].中国中药杂志,2016,41(24):4675-4679.
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[10]王亮,叶小利,李学刚,等.黄连生物碱在大鼠体内的代谢转化及分布[J].中国中药杂志,2010,35(15):2017-2020.
[11]邱峰,朱志勇,朴淑娟,等.人口服盐酸小檗碱后尿液中代谢产物的研究[J].中国医学研究与临床,2005,3(8):6-9.
[12]韩凤梅,朱明明,陈怀侠,等.液相色谱-串联电喷雾离子阱质谱法鉴定大鼠尿液中药根碱代谢物[J].药学学报,2006,41(9):846-851.
[13]朱志勇.小檗碱在人及大鼠体内代谢产物的研究[D].沈阳:沈阳药科大学,2003.
[14]杨岩涛,李森,刘金玲,等.中药质量标志物与“网通虹势”代谢规律[J].中国中药杂志,2017,42(12):2420-2424.
[2]中华人民共和国药典委员会.中华人民共和国药典[S].一部.北京:中国医药科技出版社,2015.
[3]崔学军.黄连及其有效成分的药理研究进展[J].中国药师,2006,9(5):469-470.
[4]熊程亿,施绪保,代宗顺,等.3H-小檗碱在家兔及小鼠体内的药代动力学研究[J].中国药理学通报,1989,5(5):293-296.
[5] PAN J F, YU C, ZHU D Y, et a1. Identification of three sulfate conjugate metabolites of berberine ctdofide in health volunteers’ urine after oral administration[J]. Acta Pharmacologica Sinica,2002, 21(1):77.
[6]薛宝娟,李志慧,张玉杰,等.吴茱萸次碱对5种黄连生物碱大鼠体外肝代谢的抑制作用[J].中草药,2014,45(9):1293-1296.
[7] OMURA T, STATO R. The carbon monoxide-binding piganent of liver microsomes, evidence for its hemoprotein naturel[J].Journal of Biological Chemistry, 1964,239:2370-2378.
[8] DILMAGHANIAN S, GERBER J G, FILLER S G, et al. Enantioselectivity of inhibition of cytochrome P450 3A4(CYP3A4)by ketoconazole:Testosterone and methadone as substrates[J]. Chirality, 2010, 16(2):79-85.
[9]贺福元,周宏灏,罗杰英,等.生物遗传多态性规律揭示中药材质量稳定性规律的探讨[J].中草药,2008,39(1):2-6,12.
[10]王亮,叶小利,李学刚,等.黄连生物碱在大鼠体内的代谢转化及分布[J].中国中药杂志,2010,35(15):2017-2020.
[11]邱峰,朱志勇,朴淑娟,等.人口服盐酸小檗碱后尿液中代谢产物的研究[J].中国医学研究与临床,2005,3(8):6-9.
[12]韩凤梅,朱明明,陈怀侠,等.液相色谱-串联电喷雾离子阱质谱法鉴定大鼠尿液中药根碱代谢物[J].药学学报,2006,41(9):846-851.
[13]朱志勇.小檗碱在人及大鼠体内代谢产物的研究[D].沈阳:沈阳药科大学,2003.
[14]杨岩涛,李森,刘金玲,等.中药质量标志物与“网通虹势”代谢规律[J].中国中药杂志,2017,42(12):2420-2424.