核受体调控中药-药物相互作用的研究现状
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摘要
核受体在化学药的体内代谢和药物-药物相互作用中具有重要的调控功能,而中药(TCM)具有与化学药相似的体内代谢过程,也主要经过Ⅰ相和Ⅱ相药物代谢酶的催化代谢。很多中药可通过核受体影响药物的作用靶点或药物代谢酶和转运体的功能,改变药物的药效学和药代动力学,进而导致中药-药物相互作用的发生。本文总结了核受体参与调控中药代谢以及中药-药物相互作用的研究进展,旨在为临床合理使用中药提供理论依据。
Nuclear receptors are important to the regulation of drug metabolism and drug-drug interactions caused by chemical drugs. The metabolic pathways of traditional Chinese medicines( TCMs) are very similar to that of chemical drugs. Many TCMs can affect the target of action or the function of metabolic enzymes and transporters through nuclear receptors,and alter the pharmacodynamics and pharmacokinetics of drugs,leading to the occurrence of drug-drug interactions. This review summarized the recent findings about nuclear receptors-mediated TCM-drug interactions,hoping to provide insight into the rationality of clinical usage of TCMs.
Nuclear receptors are important to the regulation of drug metabolism and drug-drug interactions caused by chemical drugs. The metabolic pathways of traditional Chinese medicines( TCMs) are very similar to that of chemical drugs. Many TCMs can affect the target of action or the function of metabolic enzymes and transporters through nuclear receptors,and alter the pharmacodynamics and pharmacokinetics of drugs,leading to the occurrence of drug-drug interactions. This review summarized the recent findings about nuclear receptors-mediated TCM-drug interactions,hoping to provide insight into the rationality of clinical usage of TCMs.
引文
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[5]YAN J,XIE W.A brief history of the discovery of PXR and CARas xenobiotic receptors[J].Acta Pharm Sin B,2016,6(5):450-452.
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[11]BALAP A,ATRE B,LOHIDASAN S,et al.Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographispaniculata(Nees)extract and andrographolide with etoricoxib after oral administration in rats[J/OL].J Ethnopharmacol,2016,183:9-17.2016-05-13[2018-09-09].https://www.sciencedirect.com/science/article/pii/S0378874115302142?via%3Dihub.
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[13]HOGLE B C,GUAN X,FOLAN M M,et al.PXR as a mediator of herb-drug interaction[J].J Food Drug Anal,2018,26(2S):S26-S31.
[14]WEI Y,TANG C,SANT V,et al.A molecular aspect in the regulation of drug metabolism:Does PXR-induced enzyme expression always lead to functional changes in drug metabolism?[J].Curr Pharmacol Rep,2016,2(4):187-192.
[15]HUANG W,ZHANG J,CHUA S S,et al.Induction of bilirubin clearance by the constitutive androstane receptor(CAR)[J].Proc Natl Acad Sci USA,2003,100(7):4156-4161.
[16]HUANG W,ZHANG J,MOORE D D.A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR[J].J Clin Invest,2004,113(1):137-143.
[17]MAITY S,NAG N,CHATTERJEE S,et al.Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthusamarus root in phenylhydrazine-induced neonatal jaundice in mice[J].J Physiol Biochem,2013,69(3):467-476.
[18]XU C,LUO M,JIANG H,et al.Involvement of CAR and PXR in the transcriptional regulation of CYP2B6 gene expression by ingredients from herbal medicines[J].Xenobiotica,2015,45(9):773-781.
[19]ZHOU X,BI H,JIN J,et al.Effects of praeruptorin A and praeruptorin C,a racemate isolated from Peucedanumpraeruptorum,on MRP2 through the CAR pathway[J].Planta Med,2013,79(17):1641-1647.
[20]LI Y,WANG Q,YAO X,et al.Induction of CYP3A4 and MDR1gene expression by baicalin,baicalein,chlorogenic acid,and ginsenosideRf through constitutive androstane receptor-and pregnane Xreceptor-mediated pathways[J].Eur J Pharmacol,2010,640(1-3):46-54.
[21]MAEDA J,INOUE K,ICHIMURA R,et al.Essential role of constitutive androstane receptor in Ginkgo biloba extract induced liver hypertrophy and hepatocarcinogenesis[J/OL].Food Chem Toxicol,2015,83:201-209.2015-06-24[2018-09-08].https://www.sciencedirect.com/science/article/pii/S0278691515001982?via%3Dihub.
[22]GRYGIEL-GORNIAK B.Peroxisome proliferator-activated receptors and their ligands:nutritional and clinical implications--a review[J/OL].Nutr J,2014,13:17.2014-02-14[2018-09-08].https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-13-17.
[23]NERURKAR P V,LEE Y K,LINDEN E H,et al.Lipid lowering effects of Momordicacharantia(Bitter Melon)in HIV-1-protease inhibitor-treated human hepatoma cells,HepG2[J].Br JPharmacol,2006,148(8):1156-1164.
[24]NHIEM N X,YEN P H,NGAN N T,et al.Inhibition of nuclear transcription factor-kappaB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordicacharantia[J].J Med Food,2012,15(4):369-377.
[25]HIEBL V,LADURNER A,LATKOLIK S,et al.Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR[J].Biotechnol Adv,2018,36(6):1657-1698.
[26]KOMATI R,SPADONI D,ZHENG S,et al.Ligands of therapeutic utility for the liver X receptors[J].Molecules,2017,22(1):pii E88.
[27]雒刚刚,路芳,乔连生,等.基于分子模拟技术筛选LXRβ中药激动剂[J].中国中药杂志,2016,41(16):3065-3071.
[28]JUN H J,HOANG M H,YEO S K,et al.Induction of ABCA1 and ABCG1 expression by the liver X receptor modulator cineole in macrophages[J].Bioorg Med ChemLett,2013,23(2):579-583.
[29]RAMADOSS P,MARCUS C,PERDEW G H.Role of the aryl hydrocarbon receptor in drug metabolism[J].Expert Opin Drug Metab Toxicol,2005,1(1):9-21.
[30]MOHEBATI A,GUTTENPLAN J B,KOCHHAR A,et al.Carnosol,a constituent of Zyflamend,inhibits aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and mutagenesis[J].Cancer Prev Res(Phila),2012,5(4):593-602.
[31]FUNAKOSHI-TAGO M,NAKAMURA K,TAGO K,et al.Antiinflammatory activity of structurally related flavonoids,Apigenin,Luteolin and Fisetin[J].Int Immunopharmacol,2011,11(9):1150-1159.
[32]ZHANG T,KIMURA Y,JIANG S,et al.Luteolin modulates expression of drug-metabolizing enzymes through the AhR and Nrf2pathways in hepatic cells[J/OL].Arch Biochem Biophys,2014,557:36-46.2014-06-07[2018-09-09].https://www.sciencedirect.com/science/article/pii/S000398611400188X?via%3Dihub.
[2]KOJETIN D J,BURRIS T P.Small molecule modulation of nuclear receptor conformational dynamics:implications for function and drug discovery[J].Mol Pharmacol,2013,83(1):1-8.
[3]PRAKASH C,ZUNIGA B,SONG C S,et al.Nuclear receptors in drug metabolism,drug response and drug interactions[J/OL].Nucl Receptor Res,2015,2:01178.2015-01-01[2018-09-09].http://europepmc.org/abstract/MED/27478824.
[4]BREWER C T,CHEN T.Hepatotoxicity of herbal supplements mediated by modulation of cytochrome P450[J].Int J Mol Sci,2017,18(11):E2353.
[5]YAN J,XIE W.A brief history of the discovery of PXR and CARas xenobiotic receptors[J].Acta Pharm Sin B,2016,6(5):450-452.
[6]CUI Z,KANG H,TANG K,et al.Screening ingredients from herbs against pregnane X receptor in the study of inductive herb-drug interactions:combining pharmacophore and docking-based rank aggregation[J/OL].Biomed Res Int,2015,2015:657159.2015-08-03[2018-09-08].https://www.hindawi.com/journals/bmri/2015/657159/.
[7]MOULY S,LLORET-LINARES C,SELLIER P O,et al.Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John’s Wort?[J/OL].Pharmacol Res,2017,118:82-92.2016-09-28[2018-09-09].https://www.sciencedirect.com/science/article/pii/S1043661816309914?via%3Dihub.
[8]XU C,HUANG M,BI H.PXR-and CAR-mediated herbal effect on human diseases[J].Biochim Biophys Acta,2016,1859(9):1121-1129.
[9]YANG J M,IP S P,XIAN Y,et al.Impact of the herbal medicine Sophoraflavescens on the oral pharmacokinetics of indinavir in rats:the involvement of CYP3A and P-glycoprotein[J/OL].PLoSOne,2012,7(2):e31312.2012-02-16[2018-09-08].https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031312.
[10]WANG L,LI F,LU J,et al.The Chinese herbal medicine Sophoraflavescens activates pregnane X receptor[J].Drug Metab Dispos,2010,38(12):2226-2231.
[11]BALAP A,ATRE B,LOHIDASAN S,et al.Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographispaniculata(Nees)extract and andrographolide with etoricoxib after oral administration in rats[J/OL].J Ethnopharmacol,2016,183:9-17.2016-05-13[2018-09-09].https://www.sciencedirect.com/science/article/pii/S0378874115302142?via%3Dihub.
[12]BALAP A,LOHIDASAN S,SINNATHAMBI A,et al.Herb-drug interaction of Andrographispaniculata(Nees)extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats[J].J Ethnopharmacol,2017,195:214-221.2017-01-04[2018-09-09].https://www.sciencedirect.com/science/article/pii/S0378874116316865?via%3Dihub.
[13]HOGLE B C,GUAN X,FOLAN M M,et al.PXR as a mediator of herb-drug interaction[J].J Food Drug Anal,2018,26(2S):S26-S31.
[14]WEI Y,TANG C,SANT V,et al.A molecular aspect in the regulation of drug metabolism:Does PXR-induced enzyme expression always lead to functional changes in drug metabolism?[J].Curr Pharmacol Rep,2016,2(4):187-192.
[15]HUANG W,ZHANG J,CHUA S S,et al.Induction of bilirubin clearance by the constitutive androstane receptor(CAR)[J].Proc Natl Acad Sci USA,2003,100(7):4156-4161.
[16]HUANG W,ZHANG J,MOORE D D.A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR[J].J Clin Invest,2004,113(1):137-143.
[17]MAITY S,NAG N,CHATTERJEE S,et al.Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthusamarus root in phenylhydrazine-induced neonatal jaundice in mice[J].J Physiol Biochem,2013,69(3):467-476.
[18]XU C,LUO M,JIANG H,et al.Involvement of CAR and PXR in the transcriptional regulation of CYP2B6 gene expression by ingredients from herbal medicines[J].Xenobiotica,2015,45(9):773-781.
[19]ZHOU X,BI H,JIN J,et al.Effects of praeruptorin A and praeruptorin C,a racemate isolated from Peucedanumpraeruptorum,on MRP2 through the CAR pathway[J].Planta Med,2013,79(17):1641-1647.
[20]LI Y,WANG Q,YAO X,et al.Induction of CYP3A4 and MDR1gene expression by baicalin,baicalein,chlorogenic acid,and ginsenosideRf through constitutive androstane receptor-and pregnane Xreceptor-mediated pathways[J].Eur J Pharmacol,2010,640(1-3):46-54.
[21]MAEDA J,INOUE K,ICHIMURA R,et al.Essential role of constitutive androstane receptor in Ginkgo biloba extract induced liver hypertrophy and hepatocarcinogenesis[J/OL].Food Chem Toxicol,2015,83:201-209.2015-06-24[2018-09-08].https://www.sciencedirect.com/science/article/pii/S0278691515001982?via%3Dihub.
[22]GRYGIEL-GORNIAK B.Peroxisome proliferator-activated receptors and their ligands:nutritional and clinical implications--a review[J/OL].Nutr J,2014,13:17.2014-02-14[2018-09-08].https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-13-17.
[23]NERURKAR P V,LEE Y K,LINDEN E H,et al.Lipid lowering effects of Momordicacharantia(Bitter Melon)in HIV-1-protease inhibitor-treated human hepatoma cells,HepG2[J].Br JPharmacol,2006,148(8):1156-1164.
[24]NHIEM N X,YEN P H,NGAN N T,et al.Inhibition of nuclear transcription factor-kappaB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordicacharantia[J].J Med Food,2012,15(4):369-377.
[25]HIEBL V,LADURNER A,LATKOLIK S,et al.Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR[J].Biotechnol Adv,2018,36(6):1657-1698.
[26]KOMATI R,SPADONI D,ZHENG S,et al.Ligands of therapeutic utility for the liver X receptors[J].Molecules,2017,22(1):pii E88.
[27]雒刚刚,路芳,乔连生,等.基于分子模拟技术筛选LXRβ中药激动剂[J].中国中药杂志,2016,41(16):3065-3071.
[28]JUN H J,HOANG M H,YEO S K,et al.Induction of ABCA1 and ABCG1 expression by the liver X receptor modulator cineole in macrophages[J].Bioorg Med ChemLett,2013,23(2):579-583.
[29]RAMADOSS P,MARCUS C,PERDEW G H.Role of the aryl hydrocarbon receptor in drug metabolism[J].Expert Opin Drug Metab Toxicol,2005,1(1):9-21.
[30]MOHEBATI A,GUTTENPLAN J B,KOCHHAR A,et al.Carnosol,a constituent of Zyflamend,inhibits aryl hydrocarbon receptor-mediated activation of CYP1A1 and CYP1B1 transcription and mutagenesis[J].Cancer Prev Res(Phila),2012,5(4):593-602.
[31]FUNAKOSHI-TAGO M,NAKAMURA K,TAGO K,et al.Antiinflammatory activity of structurally related flavonoids,Apigenin,Luteolin and Fisetin[J].Int Immunopharmacol,2011,11(9):1150-1159.
[32]ZHANG T,KIMURA Y,JIANG S,et al.Luteolin modulates expression of drug-metabolizing enzymes through the AhR and Nrf2pathways in hepatic cells[J/OL].Arch Biochem Biophys,2014,557:36-46.2014-06-07[2018-09-09].https://www.sciencedirect.com/science/article/pii/S000398611400188X?via%3Dihub.