黄酮类化合物药代动力学研究评述
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摘要
尽管国内外学者对黄酮类化合物药代动力学有诸多研究,也取得了一些成果,但是还存在一些不足之处。首先,由于中药的化学成分非常复杂,以其中的一个或几个化学成分为检测指标,导致测得的药代动力学特征不能代表整个体内过程。需要建立合适的药代动力学-药效学模型,凸显中药"多组分,多靶点"的特点,形成全面科学的研究体系。其次,黄酮类成分的药代动力学研究仍处于探索阶段,主要针对部分单体成分,且不同实验对象、不同给药途径等均会影响活性成分在体内的药代动力学行为。中药的药代动力学研究需要注意活性成分之间的相互作用。随着中药成分分析技术的发展以及对种属差异、药物代谢酶、药物代谢基因多态性等认识的不断增加,为中药相互作用的研究提供了良好的契机。
It is true that scholars at home and abroad have done many studies and made achievements on pharmacokinetics of flavonoid combined drugs. But deficiencies still exist that,firstly,the chemical composition of Chinese medicine is too complicated for researchers to interpret the whole metabolism process in human body based on the detected pharmacokinetic characteristics of one or several compositions. An appropriate drug pharmacokinetics-pharmacodynamics module should be established to match the complicated Chinese medicine,thus highlighting the " multi-component and multi-target" characteristic of Chinese medicine and forming a comprehensive and scientific research system; secondly,the researches about the pharmacokinetics of flavonoid combined drugs are still in exploration stage and mainly aim at part of the individual composition. But the pharmacokinetic behaviors of active ingredients of the drugs in human body can be influenced by different experimental objects and administration methods. Interactions between the ingredients should be emphasized in pharmacokinetic studies on Chinese medicine. Now,with the development of Chinese medicine analyzing technologies and the increasing cognition for species variation,drug metabolic enzyme and gene polymorphism of drug metabolism,the circumstances of studies on the interaction of Chinese medicine have become better and better.
It is true that scholars at home and abroad have done many studies and made achievements on pharmacokinetics of flavonoid combined drugs. But deficiencies still exist that,firstly,the chemical composition of Chinese medicine is too complicated for researchers to interpret the whole metabolism process in human body based on the detected pharmacokinetic characteristics of one or several compositions. An appropriate drug pharmacokinetics-pharmacodynamics module should be established to match the complicated Chinese medicine,thus highlighting the " multi-component and multi-target" characteristic of Chinese medicine and forming a comprehensive and scientific research system; secondly,the researches about the pharmacokinetics of flavonoid combined drugs are still in exploration stage and mainly aim at part of the individual composition. But the pharmacokinetic behaviors of active ingredients of the drugs in human body can be influenced by different experimental objects and administration methods. Interactions between the ingredients should be emphasized in pharmacokinetic studies on Chinese medicine. Now,with the development of Chinese medicine analyzing technologies and the increasing cognition for species variation,drug metabolic enzyme and gene polymorphism of drug metabolism,the circumstances of studies on the interaction of Chinese medicine have become better and better.
引文
[1]裴凌鹏,惠伯棣,金宗濂,等.黄酮类化合物的生理活性及其制备技术研究进展[J].食品科学,2004,25(2):203-207.
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[3]NG T B,HUANG B,FONG W P,et al Anti-human immunode-ficiency viruxs(anti-HIV)natrxral products with special emphasis on H1V reverse trans-criptase inhibitors[J].Life Sci,1997,61(10):933-949.
[4]刘德育,雷焕强.杨梅黄素及蛇葡萄素对酪氨酸酶的抑制作用[J].中国生物化学与分子生物学报,1996,12(5):618-620.
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[6]许兰,尹明浩.卷柏穗花杉双黄酮的舒张血管作用实验研究[J].延边大学医学学报,2009,32(4):246-248.
[7]郑晓珂,苏成福,张莉,等.卷柏中穗花杉双黄酮降血糖作用[J].中国实验方剂学杂志,2013,19(17):198-202.
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[9]赵绪元,姚金成,胡领,等.RP-高效液相色谱法测定银黄冲剂中黄芩苷在大鼠体内的血药浓度及药代动力学研究[J].天然产物研究与开发,2007,19(5):645-647.
[10]谢雁鸣,邓文龙,洪诤.骨碎补中柚皮苷大鼠体内药时过程研究[J].中药新药与临床药理,2005,16(5):350-352.
[11]周计生,陈晓青,蒋新宇,等.固相萃取-反相高效液相色谱法分析粗裂地钱中的黄酮类化合物[J].天然产物研究与开发,2012,24(10):191-194.
[12]向大雄,张杰,李焕德,等.高效液相色谱法测定犬血浆中葛根素含量[J].药物分析杂志,2004,24(6):599-601.
[13]RICKLING A,HANS B,KRAMACZYK R.Two high performance liquid chromatographic assays for the determination of free and total silibinin diastereomers in plasma using column switching with electrochemical detection and reversed-phase chromatography with ultraviolet detection[J].J Chromatogr B Biomed Appl,1995,12(2):67.
[14]张颖,刘建勋,林力,等.高效液相色谱-ECD法测定大鼠血浆中银杏叶黄酮成分及药代动力学研究[J].药物分析杂志,2011,31(1):10-14.
[15]李晰,王庆伟,梁力,等.高效液相色谱法测定大鼠血浆中根皮素及其药物代谢动力学研究[J].中成药,2013,35(3):487-490.
[16]MICHLER H,LAAKMANN G,WAGNER H.Development of an LCMS method for simultaneous quantitation of Amentoflavone and biapigenin,the minor and major biflavones from Hypericumperforatum L in human plasma and its application to real blood[J].Phytochem Anal,2011,22(1):42-50.
[17]程宏明,蔡振世,邱鹰昆,等.高效液相色谱-质谱联用法同时测定大鼠血浆中3种蟾皮主要活性成分[J].厦门大学学报(自然科学版),2012,51(3):381-385.
[18]吴彩胜,王亦琳,张金兰,等.高效液相色谱-质谱联用法测定银杏7种有效成分在犬血浆中浓度以及银杏叶酊剂的相对生物利用度[J].中国新药杂志,2013,22(1):93-99.
[19]吴胜明,安代志,方均建,等.应用液质联用技术对大鼠血浆中槲皮素的测定[J].分析测试学报,2008,27(3):199-201.
[20]郑庆红,张忠鹏,耿子颖,等.球形红细菌生物转化槲寄生中总黄酮类化合物的测定[J].中国药物与临床,2012,12(8):981-983.
[21]张宜凡,张艺竹,陈烨,等.葛根芩连汤中黄芩活性成分在大鼠体内的组织分布[J].中国实验方剂学杂志,2013,19(19):177-182.
[22]杨炳华.野黄芩苷的药物动力学及代谢研究[D].沈阳:沈阳药科大学,2004.
[23]车庆明,黄新立,李艳梅,等.黄芩苷的药物代谢产物研究[J].中国中药杂志,2001,26(11):768.
[24]闫晶超,刘兆明,王天明,等.泻心汤黄酮类成分在大鼠体内的药代动力学研究[J].药学学报,2007,42(7):722-729.
[25]和凡,钟国平,赵立子,等.LP-MS-MS法研究黄酮类化合物对人肝微粒体细胞色素P4506种亚型的体外抑制作用[J].中国新药杂志,2009,18(24):2340-2348.
[26]蔡巧玲,王莹,崔波,等.半夏泻心汤及不同配伍对大鼠肝微粒体中黄芩苷和黄芩素代谢的影响[J].中药材,2012,35(8):1286-1290.
[27]柴士伟,潘桂湘.药物代谢研究方法简述[J].天津中医药,2006,23(1):83-85.
[28]崔升淼,赵春顺.大鼠离体肝灌流中葛根素的代谢动力学研究[J].中药药理与临床,2008,24(1):17-19.
[29]王丹,石力夫,胡晋红,等.微透析联用反相高效液相色谱对大鼠皮肤葛根素的药代动力学研究[J].分析化学研究简报,2008,36(10):1391-1395.
[30]贾小进,乔爱敏.中药代谢化学研究进展[J].当代医学,2003,9(8):80-81.
[31]杨秀伟,张建业,张蔚青,等.山奈苷的人肠内细菌生物转化研究[J].药学学报,2005,40(8):717-721.
[32]LEE N K,CHOI S H,PARK S H,et al.Antiallergic activity of hesperidin is activated by intestinal microflora[J].Pharmacology,2004,71(4):174.
[33]刘萍,王平,陈刚,等.应用代谢组学探讨中医药复杂理论体系的研究思路和方法[J].中华中医药杂志,2011,26(5):993-998.
[2]毛雪石.黄酮类化合物的抗肿瘤活性[J].国外医学·药学分册,1995,22(2):92-96.
[3]NG T B,HUANG B,FONG W P,et al Anti-human immunode-ficiency viruxs(anti-HIV)natrxral products with special emphasis on H1V reverse trans-criptase inhibitors[J].Life Sci,1997,61(10):933-949.
[4]刘德育,雷焕强.杨梅黄素及蛇葡萄素对酪氨酸酶的抑制作用[J].中国生物化学与分子生物学报,1996,12(5):618-620.
[5]LEE J Y,CHOI Y J,WOO E R,et al.Docking study of biflavonoids,allosteric inhibitors of protein tyrosine phosphatase IB[J].Bull Korean Chem Soc,2008,29(8):1479-1484.
[6]许兰,尹明浩.卷柏穗花杉双黄酮的舒张血管作用实验研究[J].延边大学医学学报,2009,32(4):246-248.
[7]郑晓珂,苏成福,张莉,等.卷柏中穗花杉双黄酮降血糖作用[J].中国实验方剂学杂志,2013,19(17):198-202.
[8]龚雯.江南卷柏提取物中穗花杉双黄酮的药代动力学研究[D].武汉:湖北中医药大学,2012.
[9]赵绪元,姚金成,胡领,等.RP-高效液相色谱法测定银黄冲剂中黄芩苷在大鼠体内的血药浓度及药代动力学研究[J].天然产物研究与开发,2007,19(5):645-647.
[10]谢雁鸣,邓文龙,洪诤.骨碎补中柚皮苷大鼠体内药时过程研究[J].中药新药与临床药理,2005,16(5):350-352.
[11]周计生,陈晓青,蒋新宇,等.固相萃取-反相高效液相色谱法分析粗裂地钱中的黄酮类化合物[J].天然产物研究与开发,2012,24(10):191-194.
[12]向大雄,张杰,李焕德,等.高效液相色谱法测定犬血浆中葛根素含量[J].药物分析杂志,2004,24(6):599-601.
[13]RICKLING A,HANS B,KRAMACZYK R.Two high performance liquid chromatographic assays for the determination of free and total silibinin diastereomers in plasma using column switching with electrochemical detection and reversed-phase chromatography with ultraviolet detection[J].J Chromatogr B Biomed Appl,1995,12(2):67.
[14]张颖,刘建勋,林力,等.高效液相色谱-ECD法测定大鼠血浆中银杏叶黄酮成分及药代动力学研究[J].药物分析杂志,2011,31(1):10-14.
[15]李晰,王庆伟,梁力,等.高效液相色谱法测定大鼠血浆中根皮素及其药物代谢动力学研究[J].中成药,2013,35(3):487-490.
[16]MICHLER H,LAAKMANN G,WAGNER H.Development of an LCMS method for simultaneous quantitation of Amentoflavone and biapigenin,the minor and major biflavones from Hypericumperforatum L in human plasma and its application to real blood[J].Phytochem Anal,2011,22(1):42-50.
[17]程宏明,蔡振世,邱鹰昆,等.高效液相色谱-质谱联用法同时测定大鼠血浆中3种蟾皮主要活性成分[J].厦门大学学报(自然科学版),2012,51(3):381-385.
[18]吴彩胜,王亦琳,张金兰,等.高效液相色谱-质谱联用法测定银杏7种有效成分在犬血浆中浓度以及银杏叶酊剂的相对生物利用度[J].中国新药杂志,2013,22(1):93-99.
[19]吴胜明,安代志,方均建,等.应用液质联用技术对大鼠血浆中槲皮素的测定[J].分析测试学报,2008,27(3):199-201.
[20]郑庆红,张忠鹏,耿子颖,等.球形红细菌生物转化槲寄生中总黄酮类化合物的测定[J].中国药物与临床,2012,12(8):981-983.
[21]张宜凡,张艺竹,陈烨,等.葛根芩连汤中黄芩活性成分在大鼠体内的组织分布[J].中国实验方剂学杂志,2013,19(19):177-182.
[22]杨炳华.野黄芩苷的药物动力学及代谢研究[D].沈阳:沈阳药科大学,2004.
[23]车庆明,黄新立,李艳梅,等.黄芩苷的药物代谢产物研究[J].中国中药杂志,2001,26(11):768.
[24]闫晶超,刘兆明,王天明,等.泻心汤黄酮类成分在大鼠体内的药代动力学研究[J].药学学报,2007,42(7):722-729.
[25]和凡,钟国平,赵立子,等.LP-MS-MS法研究黄酮类化合物对人肝微粒体细胞色素P4506种亚型的体外抑制作用[J].中国新药杂志,2009,18(24):2340-2348.
[26]蔡巧玲,王莹,崔波,等.半夏泻心汤及不同配伍对大鼠肝微粒体中黄芩苷和黄芩素代谢的影响[J].中药材,2012,35(8):1286-1290.
[27]柴士伟,潘桂湘.药物代谢研究方法简述[J].天津中医药,2006,23(1):83-85.
[28]崔升淼,赵春顺.大鼠离体肝灌流中葛根素的代谢动力学研究[J].中药药理与临床,2008,24(1):17-19.
[29]王丹,石力夫,胡晋红,等.微透析联用反相高效液相色谱对大鼠皮肤葛根素的药代动力学研究[J].分析化学研究简报,2008,36(10):1391-1395.
[30]贾小进,乔爱敏.中药代谢化学研究进展[J].当代医学,2003,9(8):80-81.
[31]杨秀伟,张建业,张蔚青,等.山奈苷的人肠内细菌生物转化研究[J].药学学报,2005,40(8):717-721.
[32]LEE N K,CHOI S H,PARK S H,et al.Antiallergic activity of hesperidin is activated by intestinal microflora[J].Pharmacology,2004,71(4):174.
[33]刘萍,王平,陈刚,等.应用代谢组学探讨中医药复杂理论体系的研究思路和方法[J].中华中医药杂志,2011,26(5):993-998.