治疗心血管疾病的中药组分对转运体的调节作用研究进展
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摘要
药物在肝脏代谢过程中除代谢酶参与外,药物转运体同样也起着举足轻重的作用。除他汀类、沙坦类等心血管系统化学药对转运体会产生影响外,近年来的研究表明,一些常用于治疗心血管系统疾病的中药组分亦会影响转运体的摄取外排功能,在与西药联合应用的过程中,可能会对介导西药的肝脏转运体产生影响,从而引起药动学改变而增加药品不良反应的发生。本文从治疗心血管系统疾病的常用中药组分对转运体的影响和与其他药物联用时可能发生的药物相互作用进行介绍,为临床提高药物治疗的有效性和安全性提供依据。
In addition to the participation of metabolic enzymes in the metabolism of the liver,drug transporters also play a vital role.In addition to the effects of cardiovascular system chemicals such as statins and sartans on transporters,recent studies have shown that some components of traditional Chinese medicine(TCM) commonly used in the treatment of cardiovascular diseases can also affect the uptake and efflux function of transporters.In the course of combined application with Western medicine,the components of TCM may affect the liver transporters mediating western medicine,thereby causing pharmacokinetic changes and increasing the occurrence of adverse drug reactions.This article introduces the effects of common traditional Chinese medicine components for the treatment of cardiovascular disease on liver transporters and the possible drug interactions when combined with chemical medicines in order to provide a basis for clinically improving the effectiveness and safety of medication.
In addition to the participation of metabolic enzymes in the metabolism of the liver,drug transporters also play a vital role.In addition to the effects of cardiovascular system chemicals such as statins and sartans on transporters,recent studies have shown that some components of traditional Chinese medicine(TCM) commonly used in the treatment of cardiovascular diseases can also affect the uptake and efflux function of transporters.In the course of combined application with Western medicine,the components of TCM may affect the liver transporters mediating western medicine,thereby causing pharmacokinetic changes and increasing the occurrence of adverse drug reactions.This article introduces the effects of common traditional Chinese medicine components for the treatment of cardiovascular disease on liver transporters and the possible drug interactions when combined with chemical medicines in order to provide a basis for clinically improving the effectiveness and safety of medication.
引文
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[4] Zha W.Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases[J].J Food Drug Anal,2018,26(2S):S32-S44.
[5] 王梓宁.中医药治疗心血管病的文献计量分析[D].中国中医科学院,2013.
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[7] 刘琦,刘克辛.代谢酶和转运体介导的中药-西药相互作用的药动学机制研究进展[J].药学学报,2015,50(4):406-412.
[8] 李聃,盛莉,李燕.药物转运体的研究方法[J].药学学报,2014,49(7):963-970.
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[12] 陈芬燕,郭韧,张毕奎.丹参酮ⅡA的心血管药理作用研究进展[J].中国中药杂志,2015,40(9):1649-1653.
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[14] 温金华.丹参水溶性成分丹参素与熊果酸对瑞舒伐他汀基于OATP1B1介导转运摄取的影响与分子机制[D].南昌大学,2011.
[15] Li XX,Zhou ZW,Zhou SF.Role of P-glycoprotein in the transport of tanshinone I,one active triterpenoid from Salvia miltiorrhiza[J].Drug Metab Lett,2008,2(3):223-230.
[16] Chen X,Zhou ZW,Xue CC,et al.Role of P-glycoprotein in restricting the brain penetration of tanshinone IIA,a major active constituent from the root of Salvia miltiorrhiza Bunge,across the blood-brain barrier[J].Xenobiotica,2007,37(6):635-678.
[17] Hua WJ,Hua WX,Nan FY,et al.The influence of herbal medicine ursolic acid on the uptake of rosuvastatin mediated by OATP1B1*1a and *5[J].Eur J Drug Metab Pharmacokinet,2014,39(3):221-230.
[18] Yuan H,Feng B,Yu Y,et al.Renal organic anion transporter-mediated drug-drug interaction between gemcabene and quinapril[J].J Pharmacol Exp Ther,2009,330(1):191-197.
[19] 黎阳,张铁军,刘素香,等.人参化学成分和药理研究进展[J].中草药,2009,40(1):164-附2.
[20] 王巍,苏光悦,胡婉琦,等.近10年人参皂苷对心血管疾病的药理作用研究进展[J].中草药,2016,47(20):3736-3741.
[21] Jiang R,Dong J,Li X,et al.Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3[J].Br J Pharmacol,2015,172(4):1059-1073.
[22] Gurley BJ,Gardner SF,Hubbard MA,et al.Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly:St John′s wort,garlic oil,Panax ginseng and Ginkgo biloba[J].Drugs Aging,2005,22(6):525-539.
[23] Li N,Wang D,Ge G,et al.Ginsenoside metabolites inhibit P-glycoprotein in vitro and in situ using three absorption models[J].Planta Med,2014,80(4):290-296.
[24] Yang Z,Gao S,Wang J,et al.Enhancement of oral bioavailability of 20(S)-ginsenoside Rh2 through improved understanding of its absorption and efflux mechanisms[J].Drug Metab Dispos,2011,39(10):1866-1872.
[25] 贺兼斌,廖慧中,张贻秋,等.人参皂苷Rg3对小鼠肺腺癌多耐药的逆转作用[J].实用肿瘤杂志,2012,27(4):373-378.
[26] 张文.基于OATPs/oatps介导的麦冬皂苷D肝脏转运的分子学机制研究[D].南昌大学,2014.
[27] Chen L,Liu L,Chen Y,et al.Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix ophiopogonis[J].Xenobiotica,2018:1-22.
[28] 陈琳.麦冬主要活性成分对OATP1B1、OATP1B3转运功能的影响及其机制研究[D].南昌大学,2016.
[29] 刘晓培.基于OATPs/Oatps介导的参麦方效应组分对麦冬皂苷D肝脏转运的影响及其配伍机理研究[D].南昌大学,2016.
[30] 郭雪红.黄芪注射液的药理作用及临床应用研究进展[J].中国药房,2015,26(21):3018-3021.
[31] Huang C,Xu D,Xia Q,et al.Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II[J].J Pharm Pharmacol,2012,64(12):1741-1750.
[32] Wang PP,Xu DJ,Huang C,et al.Astragaloside Ⅳ reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines[J].Mol Med Rep,2014,9(6):2131-2137.
[33] Liu L,Li P,Qiao L,et al.Effects of astragaloside IV on the pharmacokinetics of puerarin in rats[J].Xenobiotica,2018:1-12.
[34] 刘旭,徐江平,程艳芹,等.基于谱效关系表达的中药川芎药效物质筛选[J].中国医院药学杂志,2014,34(23):1969-1973.
[35] 张翠英,章洪,戚琼华.川芎的有效成分及药理研究进展[J].辽宁中医杂志,2014,41(10):2264-2266.
[36] Zhang Y,Liu X,Zuo T,et al.Tetramethylpyrazine reverses multidrug resistance in breast cancer cells through regulating the expression and function of P-glycoprotein[J].Med Oncol,2012,29(2):534-538.
[37] Wang XB,Wang SS,Zhang QF,et al.Inhibition of tetramethylpyrazine on P-gp,MRP2,MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells[J].Oncol Rep,2010,23(1):211-215.
[38] Ma BL,Ma YM.Pharmacokinetic herb-drug interactions with traditional Chinese medicine:progress,causes of conflicting results and suggestions for future research[J].Drug Metab Rev,2016,48(1):1-26.
[39] Wu LX,Guo CX,Chen WQ,et al.Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin:an in vitro and in vivo assessment[J].Br J Clin Pharmacol,2012,73(5):750-757.
[40] Mandery K,Bujok K,Schmidt I,et al.Influence of the flavonoids apigenin,kaempferol,and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1[J].Biochem Pharmacol,2010,80(11):1746-1753.
[41] Satsu H,Hiura Y,Mochizuki K,et al.Activation of pregnane X receptor and induction of MDR1 by dietary phytochemicals[J].J Agric Food Chem,2008,56(13):5366-5373.
[42] 杨硕,佟倩.黄连素在心血管疾病中的研究进展[J].中国老年学杂志,2016,36(6):1526-1527.
[43] 张倍健,张燚,徐全福,等.小檗碱联合他汀对稳定型冠心病血浆氧化三甲胺的影响[J].临床心血管病杂志,2017,33(1):17-22.
[44] Chen C,Wu ZT,Ma LL,et al.Organic anion-transporting polypeptides contribute to the hepatic uptake of berberine[J].Xenobiotica,2015,45(12):1138-1146.
[45] 武卫党,崔涛,张星艳,等.小檗碱对有机阳离子药物转运体抑制作用研究[J].药物评价研究,2017,40(5):633-637.
[2] 马丽媛,吴亚哲,王文,等.《中国心血管病报告2017》要点解读[J].中国心血管杂志,2018,23(1):3-6.
[3] 陈灏珠,赵玉霞.心血管疾病中医药治疗的问题与对策[J].中华心血管病杂志,2011,39(8):693-694.
[4] Zha W.Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases[J].J Food Drug Anal,2018,26(2S):S32-S44.
[5] 王梓宁.中医药治疗心血管病的文献计量分析[D].中国中医科学院,2013.
[6] Sugano K,Kansy M,Artursson P,et al.Coexistence of passive and carrier-mediated processes in drug transport[J].Nat Rev Drug Discov,2010,9(8):597-614.
[7] 刘琦,刘克辛.代谢酶和转运体介导的中药-西药相互作用的药动学机制研究进展[J].药学学报,2015,50(4):406-412.
[8] 李聃,盛莉,李燕.药物转运体的研究方法[J].药学学报,2014,49(7):963-970.
[9] Zhang L,Huang SM,Lesko LJ.Transporter-mediated drug-drug interactions[J].Clin Pharmacol Ther,2011,89(4):481-484.
[10] Wessler JD,Grip LT,Mendell J,et al.The P-glycoprotein transport system and cardiovascular drugs[J].J Am Coll Cardiol,2013,61(25):2495-2502.
[11] Cheng To.Cardiovascular effects of Danshen[J].Int J Cardiol,2007,121(1):9-22.
[12] 陈芬燕,郭韧,张毕奎.丹参酮ⅡA的心血管药理作用研究进展[J].中国中药杂志,2015,40(9):1649-1653.
[13] Wang L,Sweet DH.Competitive inhibition of human organic anion transporters 1 (SLC22A6),3 (SLC22A8) and 4 (SLC22A11) by major components of the medicinal herb Salvia miltiorrhiza (Danshen)[J].Drug Metab Pharmacokinet,2013,28(3):220-228.
[14] 温金华.丹参水溶性成分丹参素与熊果酸对瑞舒伐他汀基于OATP1B1介导转运摄取的影响与分子机制[D].南昌大学,2011.
[15] Li XX,Zhou ZW,Zhou SF.Role of P-glycoprotein in the transport of tanshinone I,one active triterpenoid from Salvia miltiorrhiza[J].Drug Metab Lett,2008,2(3):223-230.
[16] Chen X,Zhou ZW,Xue CC,et al.Role of P-glycoprotein in restricting the brain penetration of tanshinone IIA,a major active constituent from the root of Salvia miltiorrhiza Bunge,across the blood-brain barrier[J].Xenobiotica,2007,37(6):635-678.
[17] Hua WJ,Hua WX,Nan FY,et al.The influence of herbal medicine ursolic acid on the uptake of rosuvastatin mediated by OATP1B1*1a and *5[J].Eur J Drug Metab Pharmacokinet,2014,39(3):221-230.
[18] Yuan H,Feng B,Yu Y,et al.Renal organic anion transporter-mediated drug-drug interaction between gemcabene and quinapril[J].J Pharmacol Exp Ther,2009,330(1):191-197.
[19] 黎阳,张铁军,刘素香,等.人参化学成分和药理研究进展[J].中草药,2009,40(1):164-附2.
[20] 王巍,苏光悦,胡婉琦,等.近10年人参皂苷对心血管疾病的药理作用研究进展[J].中草药,2016,47(20):3736-3741.
[21] Jiang R,Dong J,Li X,et al.Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3[J].Br J Pharmacol,2015,172(4):1059-1073.
[22] Gurley BJ,Gardner SF,Hubbard MA,et al.Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly:St John′s wort,garlic oil,Panax ginseng and Ginkgo biloba[J].Drugs Aging,2005,22(6):525-539.
[23] Li N,Wang D,Ge G,et al.Ginsenoside metabolites inhibit P-glycoprotein in vitro and in situ using three absorption models[J].Planta Med,2014,80(4):290-296.
[24] Yang Z,Gao S,Wang J,et al.Enhancement of oral bioavailability of 20(S)-ginsenoside Rh2 through improved understanding of its absorption and efflux mechanisms[J].Drug Metab Dispos,2011,39(10):1866-1872.
[25] 贺兼斌,廖慧中,张贻秋,等.人参皂苷Rg3对小鼠肺腺癌多耐药的逆转作用[J].实用肿瘤杂志,2012,27(4):373-378.
[26] 张文.基于OATPs/oatps介导的麦冬皂苷D肝脏转运的分子学机制研究[D].南昌大学,2014.
[27] Chen L,Liu L,Chen Y,et al.Modulation of transporter activity of OATP1B1 and OATP1B3 by the major active components of Radix ophiopogonis[J].Xenobiotica,2018:1-22.
[28] 陈琳.麦冬主要活性成分对OATP1B1、OATP1B3转运功能的影响及其机制研究[D].南昌大学,2016.
[29] 刘晓培.基于OATPs/Oatps介导的参麦方效应组分对麦冬皂苷D肝脏转运的影响及其配伍机理研究[D].南昌大学,2016.
[30] 郭雪红.黄芪注射液的药理作用及临床应用研究进展[J].中国药房,2015,26(21):3018-3021.
[31] Huang C,Xu D,Xia Q,et al.Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II[J].J Pharm Pharmacol,2012,64(12):1741-1750.
[32] Wang PP,Xu DJ,Huang C,et al.Astragaloside Ⅳ reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines[J].Mol Med Rep,2014,9(6):2131-2137.
[33] Liu L,Li P,Qiao L,et al.Effects of astragaloside IV on the pharmacokinetics of puerarin in rats[J].Xenobiotica,2018:1-12.
[34] 刘旭,徐江平,程艳芹,等.基于谱效关系表达的中药川芎药效物质筛选[J].中国医院药学杂志,2014,34(23):1969-1973.
[35] 张翠英,章洪,戚琼华.川芎的有效成分及药理研究进展[J].辽宁中医杂志,2014,41(10):2264-2266.
[36] Zhang Y,Liu X,Zuo T,et al.Tetramethylpyrazine reverses multidrug resistance in breast cancer cells through regulating the expression and function of P-glycoprotein[J].Med Oncol,2012,29(2):534-538.
[37] Wang XB,Wang SS,Zhang QF,et al.Inhibition of tetramethylpyrazine on P-gp,MRP2,MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells[J].Oncol Rep,2010,23(1):211-215.
[38] Ma BL,Ma YM.Pharmacokinetic herb-drug interactions with traditional Chinese medicine:progress,causes of conflicting results and suggestions for future research[J].Drug Metab Rev,2016,48(1):1-26.
[39] Wu LX,Guo CX,Chen WQ,et al.Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin:an in vitro and in vivo assessment[J].Br J Clin Pharmacol,2012,73(5):750-757.
[40] Mandery K,Bujok K,Schmidt I,et al.Influence of the flavonoids apigenin,kaempferol,and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1[J].Biochem Pharmacol,2010,80(11):1746-1753.
[41] Satsu H,Hiura Y,Mochizuki K,et al.Activation of pregnane X receptor and induction of MDR1 by dietary phytochemicals[J].J Agric Food Chem,2008,56(13):5366-5373.
[42] 杨硕,佟倩.黄连素在心血管疾病中的研究进展[J].中国老年学杂志,2016,36(6):1526-1527.
[43] 张倍健,张燚,徐全福,等.小檗碱联合他汀对稳定型冠心病血浆氧化三甲胺的影响[J].临床心血管病杂志,2017,33(1):17-22.
[44] Chen C,Wu ZT,Ma LL,et al.Organic anion-transporting polypeptides contribute to the hepatic uptake of berberine[J].Xenobiotica,2015,45(12):1138-1146.
[45] 武卫党,崔涛,张星艳,等.小檗碱对有机阳离子药物转运体抑制作用研究[J].药物评价研究,2017,40(5):633-637.