穿心莲内酯及其衍生物药代动力学研究进展
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摘要
穿心莲内酯为从爵床科植物穿心莲中提取得到的二萜内酯类化合物,是中药穿心莲的主要有效成分之一。近年研究表明,其多种衍生物在溶解性等方面优于原型药物,促使含穿心莲内酯及其衍生物的药物在临床上被广泛应用。该文阐述了穿心莲内酯及其衍生物的药代动力学研究进展,以为这一天然活性成分的开发和利用提供依据。
Andrographolide is a natural diterpenoid lactone compound with labdane skeleton,isolated from Andrographis paniculate( Burm) Nees.It is one of the main effective components of it.In recent years,many of its derivatives are superior to the prototype drugs in solubility,and have been used as the main components of some Chinese medicines on clinic.In this paper,the pharmacokinetics of andrographolide and its derivatives were reviewed,and the development and utilization of this natural active ingredient were provided.
Andrographolide is a natural diterpenoid lactone compound with labdane skeleton,isolated from Andrographis paniculate( Burm) Nees.It is one of the main effective components of it.In recent years,many of its derivatives are superior to the prototype drugs in solubility,and have been used as the main components of some Chinese medicines on clinic.In this paper,the pharmacokinetics of andrographolide and its derivatives were reviewed,and the development and utilization of this natural active ingredient were provided.
引文
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[3]朱艳玲.穿心莲化学成分和药理作用的研究进展[J].中国现代药物应用,2013,7(14):238-239.
[4]李克敏,刘文清,朱治本.脱水穿心莲内酯在大鼠的药代动力学[J].中药药理与临床,1990,6(1):38-40.
[5]刘峻,唐庆九,王峥涛.新穿心莲内酯对小鼠巨噬细胞呼吸爆发及淋巴细胞增殖的影响[J].中国新药与临床杂志,2005,24(3):206-209.
[6]胡中慧,吴纯启,王全军,等.莲必治注射液静脉单次给药对大鼠尿液内源性代谢物质的影响[J].药物不良反应杂志,2010,12(2):83-90.
[7]唐韵.喜炎平注射液临床应用近况[J].世界临床药物,2014,35(3):184-188.
[8] PANOSSIAN A,HOVHAMMISYAN A,MAMIKONYAN G,et al. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human[J]. Phytomedicine,2000,7(5):351-364.
[9]祝晨蔯,莫建霞,桂蜀华,等.家兔血清中穿心莲内酯的血药浓度测定[J].中药药理与临床,2002,18(4):9-11.
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[11] XU F F,FU S J,GU S P,et al.Simultaneous determination of andrographolide,dehydroandrographolide and neoandrographolide in dog plasma by LC-MS/MS and its application to a dog pharmacokinetic study of Andrographis paniculata tablet[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2015(990):125-131.
[12]高燕,王忠兰,黄桂华.炎琥宁肠溶微丸在大鼠体内肠吸收及药物动力学实验研究[J].中药材,2011,34(8):1247-1250.
[13] WANG J,YANG W,WANG G,et al.Determination of six components of Andrographis paniculata extract and one major metabolite of andrographolide in rat plasma by liquid chromatography-tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2014,(951-952):78-88.
[14]陈思敏,陈朝霞,狄红霞,等.大鼠血清中穿心莲内酯及脱水穿心莲内酯的含量测定[J].中药与临床,2011,2(4):24-26.
[15] PHOLPHANA N,PANOMVANA D,RANGKADILOK N,et al.A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis Paniculata in Human Plasma and Its Application to a Pilot Study[J].Planta Med,2016,82(1-2):113-120.
[16]叶玲.外排转运蛋白和药物代谢酶在二萜类化合物生物利用度屏障的作用及其机制[D].广州:南方医科大学,2012.
[17] YANG T,XU C,WANG Z T,et al.Comparative pharmacokinetic studies of and rographolide and its metabolite of 14-deoxy-12-hydroxy-andrographolide in rat by ultra-performance liquid chromatography-mass spectrometry[J].Biomed Chromatogr,2013,27(7):931-937.
[18]无锡市原子医学研究所,苏州医学院,无锡市第五制药厂,等.应用35硫对Na HSO3-穿心莲内酯代谢的研究[J].生物化学与生物物理学报,1979,11(1):11-18.
[19]崇岚,罗跃华,杨小玲,等.17-氢-9-去氢穿心莲内酯-19-硫酸酯钠在大鼠体内的组织分布研究[J].中成药,2013,35(11):2378-2384.
[20]汪宝琪,庞志功,尹鸿.穿心莲内酯在兔体内脏的分布研究[J].西北药学杂志,1995,10(2):56-57.
[21]金晶,赵钟祥,晏菊娇,等.亚硫酸氢钠穿心莲内酯在beagle犬体内的药动学研究[J].医药导报,2005,24(2):109-111.
[22] ZHENG D,SHAO J,CHEN W,et al.In vitro Metabolism of Sodium 9-dehydro-17-hydro-andrographolide-19-yl Sulfate in Rat Liver S9 by Liquid Chromatography–Mass Spectrometry Method[J]. Pharmacogn Mag,2016,12(Suppl 2):S102-S108.
[23]汤瑶,李佐刚,闻镍,等.超高效液相色谱-串联质谱法测定亚硫酸氢钠穿心莲内酯在大鼠肝微粒体中的含量[J].药物分析杂志,2012,32(11):1932-1939.
[24]邵军,陈伟康,郑东昆,等.17-氢-9-去氢穿心莲内酯体外代谢速率及代谢产物研究[J].中国中药杂志,2015,40(5):971-977.
[25] ZHAO H Y,HU H,WANG Y T,et al.Comparative metabolism and stability of andrographolide in liver microsomes from humans,dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transform ion cyclotron resonance mass spectrometry[J].Rapid Commun Mass Spectrom,2013,27(12):1385-1392.
[26] TIAN X,LIANG S,WANG C,et al.Erratum to:regioselective glucuronidation of andrographolide and its major derivatives:metabolite identification,isozyme contribution,and species differences[J].AAOS J,2015,17(2):479.
[27] YE L,WANG T,TANG L,et al.Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein[J]. J Pharm Sci,2011,100(11):5007-5017.
[28] YE L,LIANG F,YANG X,et al.Oral bioavailability and intestinal disposition of dehydroandrographolide in rats[J].J South Med Univ,2012,32(8):1074-1081.
[29]邸皓,文大为,李琛琛,等.LC-ESI MS分析大鼠血浆中穿心莲内酯及其代谢产物:全国有机质谱学术交流会[C].2005.
[30] HE X,LI J,GAO H,et al.Identification of a rare sulfonic acid metabolite of andrographolide in rats[J].Drug Metab Dispos,2003,31(8):983-985.
[31] CUI L,QIU F,YAO X.Isolation and identification of seven glucuronide conjugates of andrographolide in human urine[J].Drug Metab Dispos,2005,33(4):555-562.
[32] CUI L,QIU F,WANG N,et al.Four new andrographolide metabolites in human urine[J].Chem Pharm Bull(Tokyo),2004,52(6):772-775.
[33] CUI L,CHAN W,QIU F,et al.Identification of four urea adducts of andrographolide in humans[J]. Drug Metab Lett,2008,2(4):261-268.
[34] QIU F,CUI L,CHEN L X,et al.Two novel creatinine adducts of andrographolide in human urine[J].Xenobiotica,2012,42(9):911-916.
[35]朱涛,柳晓泉.穿心莲内酯磺化物E在大鼠体内的代谢及代谢动力学研究[J].中国临床药理学与治疗学,2016,21(4):404-411.
[36] CHONG L,CHEN W,LUO Y,et al.Simultaneous determination of 9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate in rat plasma by UHPLC-ESI-MS/MS after administration of xiyanping injection:application to a pharmacokinetic study[J].Biomed Chromatogr,2013,27(7):825-830.
[37]祝晨,莫建霞.穿心莲二萜内酯代谢产物初步研究[J].亚太传统医药,2005(4):80-82.
[38]王毅雄.穿心莲新苷微生物转化及在大鼠体内代谢的研究[D].沈阳:沈阳药科大学,2009.
[39] ZHANG S Q,CHEN X H,YU M,et al.Quantification of andrographolide sodium bisulphite in urine after intravenous injection to rats by LC-MS/MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,880(1):163-167.
[2] CHEN J X,XUE H J,YE W C,et al.Activity of andrographolide and its derivatives against influenza virus in vivo and in vitro[J]. Biol Pharm Bull,2009,32(8):1385-1391.
[3]朱艳玲.穿心莲化学成分和药理作用的研究进展[J].中国现代药物应用,2013,7(14):238-239.
[4]李克敏,刘文清,朱治本.脱水穿心莲内酯在大鼠的药代动力学[J].中药药理与临床,1990,6(1):38-40.
[5]刘峻,唐庆九,王峥涛.新穿心莲内酯对小鼠巨噬细胞呼吸爆发及淋巴细胞增殖的影响[J].中国新药与临床杂志,2005,24(3):206-209.
[6]胡中慧,吴纯启,王全军,等.莲必治注射液静脉单次给药对大鼠尿液内源性代谢物质的影响[J].药物不良反应杂志,2010,12(2):83-90.
[7]唐韵.喜炎平注射液临床应用近况[J].世界临床药物,2014,35(3):184-188.
[8] PANOSSIAN A,HOVHAMMISYAN A,MAMIKONYAN G,et al. Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human[J]. Phytomedicine,2000,7(5):351-364.
[9]祝晨蔯,莫建霞,桂蜀华,等.家兔血清中穿心莲内酯的血药浓度测定[J].中药药理与临床,2002,18(4):9-11.
[10] XU L,XIAO D W,LOU S,et al. A simple and sensitive HPLC-ESI-MS/MS method for the determination of andrographolide in human plasma[J].J Chromatogr B Analyt Technol Biomed Life Sci,2009,877(5-6):502-506.
[11] XU F F,FU S J,GU S P,et al.Simultaneous determination of andrographolide,dehydroandrographolide and neoandrographolide in dog plasma by LC-MS/MS and its application to a dog pharmacokinetic study of Andrographis paniculata tablet[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2015(990):125-131.
[12]高燕,王忠兰,黄桂华.炎琥宁肠溶微丸在大鼠体内肠吸收及药物动力学实验研究[J].中药材,2011,34(8):1247-1250.
[13] WANG J,YANG W,WANG G,et al.Determination of six components of Andrographis paniculata extract and one major metabolite of andrographolide in rat plasma by liquid chromatography-tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2014,(951-952):78-88.
[14]陈思敏,陈朝霞,狄红霞,等.大鼠血清中穿心莲内酯及脱水穿心莲内酯的含量测定[J].中药与临床,2011,2(4):24-26.
[15] PHOLPHANA N,PANOMVANA D,RANGKADILOK N,et al.A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis Paniculata in Human Plasma and Its Application to a Pilot Study[J].Planta Med,2016,82(1-2):113-120.
[16]叶玲.外排转运蛋白和药物代谢酶在二萜类化合物生物利用度屏障的作用及其机制[D].广州:南方医科大学,2012.
[17] YANG T,XU C,WANG Z T,et al.Comparative pharmacokinetic studies of and rographolide and its metabolite of 14-deoxy-12-hydroxy-andrographolide in rat by ultra-performance liquid chromatography-mass spectrometry[J].Biomed Chromatogr,2013,27(7):931-937.
[18]无锡市原子医学研究所,苏州医学院,无锡市第五制药厂,等.应用35硫对Na HSO3-穿心莲内酯代谢的研究[J].生物化学与生物物理学报,1979,11(1):11-18.
[19]崇岚,罗跃华,杨小玲,等.17-氢-9-去氢穿心莲内酯-19-硫酸酯钠在大鼠体内的组织分布研究[J].中成药,2013,35(11):2378-2384.
[20]汪宝琪,庞志功,尹鸿.穿心莲内酯在兔体内脏的分布研究[J].西北药学杂志,1995,10(2):56-57.
[21]金晶,赵钟祥,晏菊娇,等.亚硫酸氢钠穿心莲内酯在beagle犬体内的药动学研究[J].医药导报,2005,24(2):109-111.
[22] ZHENG D,SHAO J,CHEN W,et al.In vitro Metabolism of Sodium 9-dehydro-17-hydro-andrographolide-19-yl Sulfate in Rat Liver S9 by Liquid Chromatography–Mass Spectrometry Method[J]. Pharmacogn Mag,2016,12(Suppl 2):S102-S108.
[23]汤瑶,李佐刚,闻镍,等.超高效液相色谱-串联质谱法测定亚硫酸氢钠穿心莲内酯在大鼠肝微粒体中的含量[J].药物分析杂志,2012,32(11):1932-1939.
[24]邵军,陈伟康,郑东昆,等.17-氢-9-去氢穿心莲内酯体外代谢速率及代谢产物研究[J].中国中药杂志,2015,40(5):971-977.
[25] ZHAO H Y,HU H,WANG Y T,et al.Comparative metabolism and stability of andrographolide in liver microsomes from humans,dogs and rats using ultra-performance liquid chromatography coupled with triple-quadrupole and Fourier transform ion cyclotron resonance mass spectrometry[J].Rapid Commun Mass Spectrom,2013,27(12):1385-1392.
[26] TIAN X,LIANG S,WANG C,et al.Erratum to:regioselective glucuronidation of andrographolide and its major derivatives:metabolite identification,isozyme contribution,and species differences[J].AAOS J,2015,17(2):479.
[27] YE L,WANG T,TANG L,et al.Poor oral bioavailability of a promising anticancer agent andrographolide is due to extensive metabolism and efflux by P-glycoprotein[J]. J Pharm Sci,2011,100(11):5007-5017.
[28] YE L,LIANG F,YANG X,et al.Oral bioavailability and intestinal disposition of dehydroandrographolide in rats[J].J South Med Univ,2012,32(8):1074-1081.
[29]邸皓,文大为,李琛琛,等.LC-ESI MS分析大鼠血浆中穿心莲内酯及其代谢产物:全国有机质谱学术交流会[C].2005.
[30] HE X,LI J,GAO H,et al.Identification of a rare sulfonic acid metabolite of andrographolide in rats[J].Drug Metab Dispos,2003,31(8):983-985.
[31] CUI L,QIU F,YAO X.Isolation and identification of seven glucuronide conjugates of andrographolide in human urine[J].Drug Metab Dispos,2005,33(4):555-562.
[32] CUI L,QIU F,WANG N,et al.Four new andrographolide metabolites in human urine[J].Chem Pharm Bull(Tokyo),2004,52(6):772-775.
[33] CUI L,CHAN W,QIU F,et al.Identification of four urea adducts of andrographolide in humans[J]. Drug Metab Lett,2008,2(4):261-268.
[34] QIU F,CUI L,CHEN L X,et al.Two novel creatinine adducts of andrographolide in human urine[J].Xenobiotica,2012,42(9):911-916.
[35]朱涛,柳晓泉.穿心莲内酯磺化物E在大鼠体内的代谢及代谢动力学研究[J].中国临床药理学与治疗学,2016,21(4):404-411.
[36] CHONG L,CHEN W,LUO Y,et al.Simultaneous determination of 9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate in rat plasma by UHPLC-ESI-MS/MS after administration of xiyanping injection:application to a pharmacokinetic study[J].Biomed Chromatogr,2013,27(7):825-830.
[37]祝晨,莫建霞.穿心莲二萜内酯代谢产物初步研究[J].亚太传统医药,2005(4):80-82.
[38]王毅雄.穿心莲新苷微生物转化及在大鼠体内代谢的研究[D].沈阳:沈阳药科大学,2009.
[39] ZHANG S Q,CHEN X H,YU M,et al.Quantification of andrographolide sodium bisulphite in urine after intravenous injection to rats by LC-MS/MS[J].J Chromatogr B Analyt Technol Biomed Life Sci,2012,880(1):163-167.