淫羊藿中活性成分的代谢产物研究进展
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摘要
淫羊藿为我国传统中药,具有补肾阳、强筋骨、祛风湿的功效。淫羊藿中主要活性成分是以淫羊藿苷为代表的黄酮苷类化合物。近年来研究发现淫羊藿给药后发挥功效的物质基础主要为其活性成分的代谢产物。综述近年来国内外对淫羊藿中活性成分的代谢产物的研究方法及代谢产物研究进展,对进一步阐明淫羊藿药材的作用机制、研制新药具有直接指导意义。
Epimedii Herba is one of the traditional Chinese materia medica with the function of invigorating kidney,strengthening yang,and eliminating wind and dampness.Flavonoid glycosides of icariin as the representative,are the main active chemical components in Epimedii Herba.Recent studies have found that the material basis of these compounds may be their metabolites in vivo.The paper reviews the research progress in the metabolites of the active constituents in Epimedii Herba,which could provide the effective guidance for further understanding their mechanism and the development of the related drugs.
Epimedii Herba is one of the traditional Chinese materia medica with the function of invigorating kidney,strengthening yang,and eliminating wind and dampness.Flavonoid glycosides of icariin as the representative,are the main active chemical components in Epimedii Herba.Recent studies have found that the material basis of these compounds may be their metabolites in vivo.The paper reviews the research progress in the metabolites of the active constituents in Epimedii Herba,which could provide the effective guidance for further understanding their mechanism and the development of the related drugs.
引文
[1]中国药典[S].一部.2010:306-308.
[2]张国辉,马辰.黄酮类化合物药动学研究进展[J].中草药,2004,35(5):582-585.
[3]Chen Y,Wang J,Jia X,Tan X,et al.Role of intestinal hydrolase in the absorption of prenylated flavonoids present in Yinyanghuo[J].Molecules,2011,16(2):1336-1348.
[4]叶丽卡,陈济民,刘四海,等.淫羊藿苷在大鼠体内的药代动力学[J].中国药学杂志,1999,34(1):33-36.
[5]Xu W,Zhang Y,Yang M,et al.LC-MS/MS method for the simultaneous determination of icariin and its major metabolites in rat plasma[J].J Pharm Biomed Anal,2007,45(4):667-672.
[6]刘健,楼宜嘉.淫藿苷体内外代谢行为及其代谢产物相关活性研究[D].杭州:浙江大学,2004.
[7]王亚乐,贾晓斌.淫羊藿黄酮苷类物理、生物转化及其机理研究[D].镇江:江苏大学,2008.
[8]Zhao Y H,Abraham M H,Le J,et al.Evaluation of rat intestinal absorption data and correlation with human intestinal absorption[J].Eur J Med Chem,2003,38(3):233-243.
[9]邱峰,陈英杰,鹿野美弘,等.淫羊藿苷在大鼠体内的代谢[J].药学学报,1999,34(3):222-226.
[10]赵艳红,贾晓斌.主成分肠吸收代谢动力学研究淫羊藿炮制机理[D].镇江:江苏大学,2007.
[11]刘铁汉,王毅,吴立军,等.淫羊藿苷的肠菌代谢研究Ⅰ.肠内细菌对淫羊藿苷的代谢转化[J].中草药,2000,31(11):834-837.
[12]邹节明,孟杰,彦正华,等.中药复方有效成分淫羊藿苷的药代动力学研究[J].中草药,2002,33(1):55-58.
[13]Zhang Y P,Xu W,Li N,et al.LC-MS-MS method for simultaneous determination of icariin and its active metabolite icariside II in human plasma[J].Chromatographia,2008,68(3/4):245-250.
[14]Liu J,Lou Y J.Determination of icariin and metabolites in rat serum by capillary zone electrophoresis:rat pharmacokinetic studies after administration of icariin[J].J Pharm Biomed Anal,2004,36(2):365-370.
[15]吴彩胜,周同惠.淫羊藿有效成分分析及其体内代谢的研究[D].北京:北京协和医学院,2011.
[16]刘海培,孟繁华,郭继芬,等.HPLC-MS/MS法分析大鼠体内淫羊藿素葡糖醛酸结合物[J].质谱学报,2010,31(6):376-379.
[17]陈彦,贾晓斌,谭晓斌,等.大鼠在体肠灌流模型研究淫羊藿不同黄酮苷的吸收代谢[J].中国中药杂志,2009,34(22):2928-2931.
[18]蔡垠,贾晓斌,陈彦,等.大鼠原位单向肠灌注模型研究淫羊藿苷肠吸收代谢特性[J].中国药学杂志,2009,44(13):985-988.
[19]Liu Y,Liu Y,Dai Y,et al.Enteric disposition and recycling of flavonoids and ginkgo flavonoids.[J].J Altern Complement Med,2003,9(5):631-640.
[20]Jeong E J,Jia X,Hu M.Disposition of formononetin via enteric recycling:metabolism and excretion in mouse intestinal perfusion and Caco-2cell models[J].Mol Pharm,2005,2(4):319-328.
[21]Chen Y,Zhao Y H,Jia X B,et al.Intestinal absorption mechanisms of prenylated flavonoids present in the heat-processed Epimedium koreanum Nakai(Yin Yanghuo)[J].Pharm Res,2008,25(9):2190-2199.
[22]赵艳红,贾晓斌,陈彦.淫羊藿黄酮类化合物的大鼠在体肠吸收研究[J].中国药学杂志,2008,43(3):188191.
[23]常琪,王庚南,李妍,等.淫羊藿素在大鼠体内的吸收与排泄[C].2011年中国药学大会暨第11届中国药师周论文集,烟台:中国药学会,2011.
[24]徐文,张亚萍,张卫东,等.离体大鼠肠道菌群对淫羊藿苷的代谢研究[J].世界科学技术:中医药现代化,2006,8(6):98-100.
[25]Yao Z H,Liu M Y,Dai Y,et al.Metabolism of Epimedium-derived flavonoid glycosides in intestinal flora of rabbits and its inhibition by gluconolactone[J].Chin J Nat Med,2011,9(6):461-465.
[26]刘晓燕,郭瑞臣.淫羊藿苷体内处置及代谢动力学研究[D].济南:山东大学,2009.
[27]张依,姚志红,秦子飞.LC-MS/MS测定家兔胆汁中淫羊藿次苷Ⅱ[J].暨南大学学报:自然科学与医学版,2012,33(3):305-310.
[28]Shen P,Wong S P,Li J,et al.Simple and sensitive liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of five Epimedium prenylflavonoids in rat sera[J].J Chromatogr B Analyt Technol Biomed Life Sci,2009,877(1/2):71-78.
[29]Wong S P,Shen P,Lee L,et al.Pharmacokinetics of prenylflavonoids and correlations with the dynamics of estrogen action in sera following ingestion of a standardized Epimedium extract[J].J Pharm Biomed Anal,2009,50(2):216-223.
[30]孟华,王广基,孙建国,等.体外及在体方法研究淫羊藿苷吸收特性和机制[J].中国药理学通讯,2004,21(3):45-46.
[31]Liu M,Liu H,Lu X,et al.Simultaneous determination of icariin,icariside II and osthole in rat plasma after oral administration of the extract of Gushudan(a Chinese compound formulation)by LC-MS/MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,860(1):113-120.
[32]Li F,Lu X,Liu H,et al.A pharmaco-metabonomic study on the therapeutic basis and metabolic effects of Epimedium brevicornum Maxim.on hydrocortisone-induced rat using UPLC-MS[J].Biomed Chromatogr,2007,21(4):397-405.
[33]Gong Y,Yip S C,Thamarai S K,et al.Trace analysis of icariin in human serum with dansyl chloride derivatization after oral administration of Epimedium decoction by liquid chromatography tandem mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,860(2):166-172.
[34]邓桂凤,姚彤伟.七藿通窍片的质量分析及其代谢动力学研究[D].杭州:浙江大学,2010.
[35]Shen P,Wong S P,and Yong E.Sensitive and rapid method to quantify icaritin and desmethylicaritin in human serum using gas chromatography-mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,857(1):47-52.
[36]赵春丽,刘建芳,刘会臣.中药药物动力学研究进展[J].解放军药学学报,2003,19(2):125-128.
[37]Pozharitskaya O N,Karlina M V,Shikov A N,et al.Determination of icariin in rat plasma by reverse-phase high-performance liquid chromatography after oral administration of a lipid-based suspension of Epimedium koreanum extract[J].Biomed Chromatogr,2008,22(6):625-629.
[38]Cheng S,Qiu F,Wang S,et al.HPLC analysis and pharmacokinetics of icariin in rats[J].J Sep Sci,2007,30(9):1307-1312.
[39]刘子琛,徐英,陈世忠.淫羊藿次苷Ⅰ在大鼠体内的药动学和组织分布研究[J].中国药学杂志,2009,43(11):848-851.
[2]张国辉,马辰.黄酮类化合物药动学研究进展[J].中草药,2004,35(5):582-585.
[3]Chen Y,Wang J,Jia X,Tan X,et al.Role of intestinal hydrolase in the absorption of prenylated flavonoids present in Yinyanghuo[J].Molecules,2011,16(2):1336-1348.
[4]叶丽卡,陈济民,刘四海,等.淫羊藿苷在大鼠体内的药代动力学[J].中国药学杂志,1999,34(1):33-36.
[5]Xu W,Zhang Y,Yang M,et al.LC-MS/MS method for the simultaneous determination of icariin and its major metabolites in rat plasma[J].J Pharm Biomed Anal,2007,45(4):667-672.
[6]刘健,楼宜嘉.淫藿苷体内外代谢行为及其代谢产物相关活性研究[D].杭州:浙江大学,2004.
[7]王亚乐,贾晓斌.淫羊藿黄酮苷类物理、生物转化及其机理研究[D].镇江:江苏大学,2008.
[8]Zhao Y H,Abraham M H,Le J,et al.Evaluation of rat intestinal absorption data and correlation with human intestinal absorption[J].Eur J Med Chem,2003,38(3):233-243.
[9]邱峰,陈英杰,鹿野美弘,等.淫羊藿苷在大鼠体内的代谢[J].药学学报,1999,34(3):222-226.
[10]赵艳红,贾晓斌.主成分肠吸收代谢动力学研究淫羊藿炮制机理[D].镇江:江苏大学,2007.
[11]刘铁汉,王毅,吴立军,等.淫羊藿苷的肠菌代谢研究Ⅰ.肠内细菌对淫羊藿苷的代谢转化[J].中草药,2000,31(11):834-837.
[12]邹节明,孟杰,彦正华,等.中药复方有效成分淫羊藿苷的药代动力学研究[J].中草药,2002,33(1):55-58.
[13]Zhang Y P,Xu W,Li N,et al.LC-MS-MS method for simultaneous determination of icariin and its active metabolite icariside II in human plasma[J].Chromatographia,2008,68(3/4):245-250.
[14]Liu J,Lou Y J.Determination of icariin and metabolites in rat serum by capillary zone electrophoresis:rat pharmacokinetic studies after administration of icariin[J].J Pharm Biomed Anal,2004,36(2):365-370.
[15]吴彩胜,周同惠.淫羊藿有效成分分析及其体内代谢的研究[D].北京:北京协和医学院,2011.
[16]刘海培,孟繁华,郭继芬,等.HPLC-MS/MS法分析大鼠体内淫羊藿素葡糖醛酸结合物[J].质谱学报,2010,31(6):376-379.
[17]陈彦,贾晓斌,谭晓斌,等.大鼠在体肠灌流模型研究淫羊藿不同黄酮苷的吸收代谢[J].中国中药杂志,2009,34(22):2928-2931.
[18]蔡垠,贾晓斌,陈彦,等.大鼠原位单向肠灌注模型研究淫羊藿苷肠吸收代谢特性[J].中国药学杂志,2009,44(13):985-988.
[19]Liu Y,Liu Y,Dai Y,et al.Enteric disposition and recycling of flavonoids and ginkgo flavonoids.[J].J Altern Complement Med,2003,9(5):631-640.
[20]Jeong E J,Jia X,Hu M.Disposition of formononetin via enteric recycling:metabolism and excretion in mouse intestinal perfusion and Caco-2cell models[J].Mol Pharm,2005,2(4):319-328.
[21]Chen Y,Zhao Y H,Jia X B,et al.Intestinal absorption mechanisms of prenylated flavonoids present in the heat-processed Epimedium koreanum Nakai(Yin Yanghuo)[J].Pharm Res,2008,25(9):2190-2199.
[22]赵艳红,贾晓斌,陈彦.淫羊藿黄酮类化合物的大鼠在体肠吸收研究[J].中国药学杂志,2008,43(3):188191.
[23]常琪,王庚南,李妍,等.淫羊藿素在大鼠体内的吸收与排泄[C].2011年中国药学大会暨第11届中国药师周论文集,烟台:中国药学会,2011.
[24]徐文,张亚萍,张卫东,等.离体大鼠肠道菌群对淫羊藿苷的代谢研究[J].世界科学技术:中医药现代化,2006,8(6):98-100.
[25]Yao Z H,Liu M Y,Dai Y,et al.Metabolism of Epimedium-derived flavonoid glycosides in intestinal flora of rabbits and its inhibition by gluconolactone[J].Chin J Nat Med,2011,9(6):461-465.
[26]刘晓燕,郭瑞臣.淫羊藿苷体内处置及代谢动力学研究[D].济南:山东大学,2009.
[27]张依,姚志红,秦子飞.LC-MS/MS测定家兔胆汁中淫羊藿次苷Ⅱ[J].暨南大学学报:自然科学与医学版,2012,33(3):305-310.
[28]Shen P,Wong S P,Li J,et al.Simple and sensitive liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of five Epimedium prenylflavonoids in rat sera[J].J Chromatogr B Analyt Technol Biomed Life Sci,2009,877(1/2):71-78.
[29]Wong S P,Shen P,Lee L,et al.Pharmacokinetics of prenylflavonoids and correlations with the dynamics of estrogen action in sera following ingestion of a standardized Epimedium extract[J].J Pharm Biomed Anal,2009,50(2):216-223.
[30]孟华,王广基,孙建国,等.体外及在体方法研究淫羊藿苷吸收特性和机制[J].中国药理学通讯,2004,21(3):45-46.
[31]Liu M,Liu H,Lu X,et al.Simultaneous determination of icariin,icariside II and osthole in rat plasma after oral administration of the extract of Gushudan(a Chinese compound formulation)by LC-MS/MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,860(1):113-120.
[32]Li F,Lu X,Liu H,et al.A pharmaco-metabonomic study on the therapeutic basis and metabolic effects of Epimedium brevicornum Maxim.on hydrocortisone-induced rat using UPLC-MS[J].Biomed Chromatogr,2007,21(4):397-405.
[33]Gong Y,Yip S C,Thamarai S K,et al.Trace analysis of icariin in human serum with dansyl chloride derivatization after oral administration of Epimedium decoction by liquid chromatography tandem mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,860(2):166-172.
[34]邓桂凤,姚彤伟.七藿通窍片的质量分析及其代谢动力学研究[D].杭州:浙江大学,2010.
[35]Shen P,Wong S P,and Yong E.Sensitive and rapid method to quantify icaritin and desmethylicaritin in human serum using gas chromatography-mass spectrometry[J].J Chromatogr B Analyt Technol Biomed Life Sci,2007,857(1):47-52.
[36]赵春丽,刘建芳,刘会臣.中药药物动力学研究进展[J].解放军药学学报,2003,19(2):125-128.
[37]Pozharitskaya O N,Karlina M V,Shikov A N,et al.Determination of icariin in rat plasma by reverse-phase high-performance liquid chromatography after oral administration of a lipid-based suspension of Epimedium koreanum extract[J].Biomed Chromatogr,2008,22(6):625-629.
[38]Cheng S,Qiu F,Wang S,et al.HPLC analysis and pharmacokinetics of icariin in rats[J].J Sep Sci,2007,30(9):1307-1312.
[39]刘子琛,徐英,陈世忠.淫羊藿次苷Ⅰ在大鼠体内的药动学和组织分布研究[J].中国药学杂志,2009,43(11):848-851.