白杨素在模式生物斑马鱼中的代谢研究

韦英杰,贾晓斌*,詹扬,王长梅,陈斌

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (7) : 565-568.

PDF(840 KB)
PDF(840 KB)
中国药学杂志 ›› 2013, Vol. 48 ›› Issue (7) : 565-568. DOI: 10.11669/cpj.2013.07.017
论著

白杨素在模式生物斑马鱼中的代谢研究

  • 韦英杰,贾晓斌*,詹扬,王长梅,陈斌
作者信息 +

Metabolism Study of Chrysin by Zebrafish

  • WEI Ying-jie, JIA Xiao-bin*, ZHAN Yang, WANG Chang-mei, CHEN Bin
Author information +
文章历史 +

摘要

目的 采用模式生物斑马鱼研究白杨素的代谢,探索斑马鱼用于研究药物Ⅱ相代谢的可行性及合理性。方法 将斑马鱼暴露于白杨素溶液中,定时取鱼体及药液,采用高效液相色谱-电喷雾质谱联用检测,根据正、负离子模式准分子离子峰获得化合物相对分子质量信息,通过与文献数据或对照品对照,推测代谢产物。结果 在斑马鱼体内或体外药液检测到白杨素原形及其2个单羟基葡萄糖醛酸结合物和1个单羟基硫酸结合物。结论 斑马鱼对白杨素的代谢与白杨素已有体内、体外的Ⅱ相代谢机制高度一致,提示斑马鱼用于药物Ⅱ相代谢具合理性,更具有化合物用量少、成本低、方法简单、高效的优势,为建立一种模式的、生物的在体药物代谢新模型提供重要参考价值。

Abstract

OBJECTIVE To study the metabolism of chrysin by model organism zebrafish for the first time, thus to investigate the reasonability of applying zebrafish in drug phase II metabolism.METHODS Zebrafish was exposed to chrysin solution for 24 h, and the samples of solution and zebrafish body were analyzed by high performance liquid chromatography-electrospray mass spectrometry (HPLC-ESI-MS) method. The quasi-molecular ions of compounds in both negative and positive mode were observed for molecule mass information, and the potential structures of the compounds were identified by studying on the mass spectra and comparing with reference data or standards.RESULTS In addition to the parent compound, three phase II metabolites were identified,including two glucuronidation products and one sulfation product.CONCLUSION The metabolism of chrysin in zebrafish is highly consistent with that identified by current in vivo and in vitro methods, which indicates that it is reasonable using zebrafish to sutdy phase II metabolism. Zebrafish model has the advantages of using far less amount of compound, lower cost, higher efficiency and simple procedure, which may become a novel organism model for quick predication of metabolism of compounds and enrich the available models greatly.

关键词

斑马鱼 / 白杨素 / 代谢 / 高效液相色谱-电喷雾质谱

Key words

zebrafish / chrysin / metabolism / high performance liquid chromatography-electrospray mass spectrometry

引用本文

导出引用
韦英杰,贾晓斌*,詹扬,王长梅,陈斌. 白杨素在模式生物斑马鱼中的代谢研究[J]. 中国药学杂志, 2013, 48(7): 565-568 https://doi.org/10.11669/cpj.2013.07.017
WEI Ying-jie, JIA Xiao-bin*, ZHAN Yang, WANG Chang-mei, CHEN Bin. Metabolism Study of Chrysin by Zebrafish[J]. Chinese Pharmaceutical Journal, 2013, 48(7): 565-568 https://doi.org/10.11669/cpj.2013.07.017
中图分类号: R969.1   

参考文献

[1] GOLDSMITH P. Zebrafish as a pharmacological toolThe how, why and when. Curr Opin Pharm, 2004, 4(5):504-512.

[2] LIANG A. Zebrafish--useful model for pharmacodynamics and toxicity screening of traditional Chinese medicine. Chin J Chin Mater Med(中国中药杂志), 2009, 34(22):2839-2842.

[3] SUKARDI H, CHNG H T, CHAN E C Y, et al. Zebrafish for drug toxicity screeningBridging the in vitro cell-based models and in vivo mammalian models. Expert Opin Drug Metab Toxicol, 2011, 7(5):579-589.

[4] KITAMBI S S, NILSSON E S, SEKYROVA P, et al. Small molecule screening platform for assessment of cardiovascular toxicity on adult zebrafish heart. BMC Physiol, 2012, 12(1):3-9.

[5] CHEN Q X, ZENG S. Research progress of zebrafish used in drug metabolism. Acta Pharm Sin(药学学报), 2011, 46(9):1026-1031.

[6] THOMPSON E D, BURWINKEL K E, CHAVA A K, et al. Activity of Phase I and Phase II enzymes of the benzo pyrene transformation pathway in zebrafish (Danio rerio) following waterborne exposure to arsenite. Comp Biochem Physiol C Toxicol Pharmacol, 2010, 152(3):371-378.

[7] ALMEIDA D V, DA SILVA NORNBERG B F, GERACITANO L A, et al. Induction of phase Ⅱ enzymes and hsp70 genes by copper sulfate through the electrophile-responsive element (EpRE)Insights obtained from a transgenic zebrafish model carrying an orthologous EpRE sequence of mammalian origin. Fish Physiol Biochem, 2010, 36(3):347-353.

[8] BRESOLIN T, DE FREITAS REBELO M, CELSO DIAS BAINY A. Expression of PXR, CYP3A and MDR1 genes in liver of zebrafish. Comp Biochem Physiol C Toxicol Pharmacol, 2005, 140(3):403-407.

[9] JIANG J S, WEI Y J, JIA X B, et al. Advances in studies on pharmacological effect and structure-activity relationship of chrysin and its derivatives. Chin Tradit Herb Drugs(中草药), 2011, 42(11):2345-2350.

[10] WALLE T, OTAKE Y, BRUBAKER J A, et al. Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br J Clin Pharmacol, 2001, 51(2):143-146.

[11] WALLE U K, GALIJATOVIC A, WALLE T. Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2. Biochem Pharmacol, 1999, 58(3):431-438.

[12]GALIJATOVIC A, OTAKE Y, WALLE U K, et al. Extensive metabolism of the flavonoid chrysin by human Caco-2 and Hep G2 cells. Xenobiotica, 1999, 29(12):1241-1256.

[13] SINGH R, WU B, TANG L, et al. Identification of the position of mono-O-glucuronide of flavones and flavonols by analyzing shift in online UV spectrum (lambdamax) generated from an online diode array detector. J Agric Food Chem, 2010, 58(17):9384-9395.

[14] WONG Y C, ZHANG L, LIN G, et al. Intestinal first-pass glucuronidation activities of selected dihydroxyflavones. Int J Pharm, 2009, 366(1-2):14-20.

[15] ZHOU Y, LU L, LI Z, et al. Antidepressant-like effects of the fractions of Xiaoyaosan on rat model of chronic unpredictable mild stress. J Ethnopharmacol, 2011, 137(1):236-244.

[16] TANG B, DING J, WU F, et al. H-NMR-based metabonomics study of the urinary biochemical changes in Kansui treated rat. J Ethnopharmacol, 2012, 141(1):134-142.

[17] WEI Y J, NING Q, JIA X B, et al. Thoughts and methods for metabol ic study of Chinese materia medica based on zebrafish model. Chin Tradit Herb Drugs(中草药), 2009, 40(7):1009-1011.

基金

国家自然科学基金资助项目(30973978);江苏省中医药领军人才专项资助项目

PDF(840 KB)

78

Accesses

0

Citation

Detail

段落导航
相关文章

/