基于化学、体内过程和代谢组学的甘草解毒作用研究概况
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摘要
甘草是一味可以解百毒、调和诸药的中药。通过研究甘草对有毒中药/毒性成分及其体内变化过程的影响和甘草对生物体内小分子代谢物的作用来探索其配伍减毒的机制,有助于更好地认识甘草与有毒中药/毒性成分的配伍规律。主要从化学、药动学和代谢组学3个方面介绍了甘草减缓有毒中药/毒性成分的作用及相关机制。
Licorice is a Chinese medicine which has the effects of reconciling various medicines and resolving hundreds of toxins. Its mechanism of compatibility and attenuation is explored by studying the effects of licorice on toxic Chinese medicines/components and their changing process in vivo and on small molecule metabolites in vivo, so as to better understand the laws of compatibility of licorice with other toxic Chinese medicines/components. In this paper, the effects of licorice on toxic Chinese medicines/components and related mechanisms are introduced from three aspects: chemistry, pharmacokinetics,and metabolomics.
Licorice is a Chinese medicine which has the effects of reconciling various medicines and resolving hundreds of toxins. Its mechanism of compatibility and attenuation is explored by studying the effects of licorice on toxic Chinese medicines/components and their changing process in vivo and on small molecule metabolites in vivo, so as to better understand the laws of compatibility of licorice with other toxic Chinese medicines/components. In this paper, the effects of licorice on toxic Chinese medicines/components and related mechanisms are introduced from three aspects: chemistry, pharmacokinetics,and metabolomics.
引文
[1]中华人民共和国药典委员会.中华人民共和国药典.一部[M].北京:中国医药科技出版社,2015:86-87.
[2]郑雪峰,赵运峰.甘草化学成分及药理作用分析[J].中国保健营养,2017,27(10):328-329.
[3]唐进法.马钱子配伍甘草前后汤液中生物碱含量变化[J].航空航天医药,2010,21(8):1529.
[4]杨明,刘小彬,黄庆德.附子甘草配伍减毒增效机理探析[J].时珍国医国药,2003,14(4):197-198.
[5]张来新,陈琦.植根深远的超分子化学[J].化工科技,2018,26(1):63-66.
[6]贺福元,周逸群,邓凯文,等.超分子化学对中医药理论的特殊影响[J].中国中药杂志,2014,39(8):1534-1543.
[7] TIAN Q, WANG X H, WANG W, et al. Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid[J]. Nanomedicine Nanotechnology Biology&Medicine, 2012, 8(6):870-879.
[8] ZHANG J, ZHANG M, JI J, et al. Glycyrrhetinic acid-mediated polymeric drug delivery targeting the acidic microenvironment of hepatocellular carcinoma[J]. Pharmaceutical Research, 2015,32(10):3376-3390.
[9]何乃普,逯盛芳,赵伟刚,等.基于蛋白质分子自组装体系的构建[J].化学进展,2014,26(z1):303-309.
[10] KE L J, GAO G Z, SHEN Y, et al. Encapsulation of aconitine in self-assembled licorice protein nanoparticles reduces the toxicity in vivo[J]. Nanoscale Research Letters, 2015, 10(1):449.
[11] SAKIYA Y, AKADA Y, KAWANO S, et al. Rapid estimation of glycyrrhizin and glycyrrhetinic acid in plasma by high-speed liquid chromatography[J]. Chemical&Pharmaceutical Bulletin,1979, 27(5):1125-1129.
[12]孙成春.HPLC法测定健康志愿者甘草甜素的药动学特征[J].国外医学:药学分册,1993(4):250-251.
[13]李锐,晏亦林,周莉玲,等.四逆汤的药动学研究[J].中成药,2002,24(10):777-780.
[14]黄洁,谭牛仔,贺龙刚,等.甘草与乌头液对小鼠乌头毒量药动学参数的影响[J].湖南中医药大学学报,2007,27(5):53-54.
[15] WANG W, WANG C, GU S, et al. Pharmacokinetic Studies of the Significance of Herbaceous Compatibility of Peony Liquorice Decoction[J]. World Science&Technology, 2009, 11(3):382-387.
[16]张锐,李青,刘芳,等.LC-MS/MS法研究甘草对雷公藤内酯酮药代动力学及组织分布与排泄的影响[J].药物分析杂志,2010,16(9):151-156.
[17]韩刚,康欣,翟冠钰,等.甘草与大黄配伍对大黄酸在大鼠体内药动学的影响[J].中国实验方剂学杂志,2010,16(9):72-74.
[18]章津铭,傅超美,秦素红,等.LC-MS/MS比较研究附子配伍甘草对大鼠体内次乌头碱药动学影响[J].世界科学技术-中医药现代化,2011,13(6):1048-1053.
[19]李菊花,蔡文涛,陈勇,等.拉米夫定与甘草次酸合用的大鼠药动学研究[J].湖北大学学报(自然科学版),2011,33(1):115-118.
[20]漆林艳,黄亮,杨宝春,等.甘草甜素对大鼠体内苦参碱药动学的影响[J].中国药房,2012,23(11):985-986.
[21]王志琪,曾嵘,谭志荣,等.附子与甘草配伍前后乌头碱和甘草次酸在大鼠体内的药动学比较[J].中成药,2012,34(12):2305-2309.
[22] SHI L, TANG X, DANG X, et al. Investigating herb-herb interactions:the potential attenuated toxicity mechanism of the combined use of Glycyrrhizae radix et rhizoma(Gancao)and Sophoraeflavescentis radix(Kushen)[J]. Journal of Ethnopharmacology, 2015, 165(4):243-250.
[23] ZHOU B, ZHANG J, WU S, et al. The influence of compatibility of processed radix AconitiKusnezoffii, on the pharmacokinetic of four components in Glycyrrhizauralensis, Fisch[J]. Journal of Ethnopharmacology, 2015, 169(8):1-7.
[24]杨锐,李金良,王斌,等.甘草提取物对左氧氟沙星在大鼠体内药动学及组织分布的影响[J].中国兽药杂志,2016,50(3):35-38.
[25]卫平,马钦海,任孟月,等.配伍对麻黄甘草药对中麻黄类生物碱在大鼠体内组织分布的影响[J].药学研究,2016,35(4):187-192.
[26] ZHANG M, DENG Y, WANG C, et al. An LC–MS/MS method for determination of bioactive componentsof liquorice and Semen Strychni in rat plasma:Applicationto a pharmacokinetics study[J]. Drug Test Anal, 2018, 10(2):262-271.
[27] SUN S, CHEN Q, GE J, et al. Pharmacokinetic interaction of aconitine, liquiritin and 6-gingerol in a traditional Chinese herbal formula, Sini Decoction[J]. Xenobiotica, 2018, 48(1):1-8.
[28] GU L, WANG X, LIU Z, et al. A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or RhizomaLigustici extract on the comparative toxicokinetics of strychnine and brucine in rats[J].Food&Chemical Toxicology An International Journal Published for the British Industrial Biological Research Association,2014, 68(4):226-233.
[29]王敏,齐云.Caco-2细胞模型及其在药物吸收研究中的应用新进展[J].中国药学杂志,2007,42(16):1201-1204.
[30] VERHALEN B, DASTVAN R, THANGAPANDIAN S, et al. Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein[J]. Nature, 2017, 543(7647):738-741.
[31]彭燕,谭晓斌,贾晓斌.甘草黄酮类成分对Caco-2细胞P-糖蛋白功能和表达的影响[J].中草药,2013,44(19):2703-2709.
[32]何丹,颜苗,李焕德,等.甘草提取物及其主要成分对Caco-2细胞膜上P-gp功能和表达的影响[J].中国药学杂志,2010,45(10):751-755.
[33]叶敏.马钱子碱、次乌头碱的体外吸收机制及其它们分别与甘草苷的转运相互作用研究[D].武汉:湖北大学,2012.
[34] GUENGERICH F P. Cytochrome p450 and chemical toxicology[J].Chemical Research in Toxicology, 2008, 21(1):70-83.
[35] BROWN C M, REISFELD B, MAYENO A N. Cytochromes P450:a structure-based summary of biotransformations using representative substrates[J]. Drug Metabolism Reviews, 2008, 40(1):91-100.
[36]徐硕,徐文峰,金鹏飞,等.甘草对药物代谢酶以及化学药物体内代谢的影响[J].中南药学,2017,15(3):329-334.
[37]刘星雨.甘草水提物对细胞色素P450酶主要亚型的表达影响及其对雷公藤内酯醇的减毒增效作用[D].镇江:江苏大学,2014.
[38]邢盼盼,吴文华,杜鹏,等.马钱子碱与甘草次酸、甘草苷配伍后对大鼠肝脏CYP450的影响[J].药学学报,2011,36(5):573-580.
[39]涂江华.甘草酸对CYP450酶的影响及其机制研究[D].长沙:中南大学,2010.
[40] HYE G J, HO J Y, SUNG J P, et al. Hepatoprotective effects of 18β-glycyrrhe-dnicaeid on carbon tetrachloride-induced liver injury:inhibition of cyt-ochrome P4502E1 expression[J]. Pharnacological Research,2002, 46(3):221-227.
[41]熊月琴.甘草次酸对大鼠肝脏CYP450酶基因表达与蛋白活性的影响[D].武汉:湖北大学,2010.
[42] LI H Y, XU W, SU J, et al. In vitro and in vivo inhibitory effects of glycyrrhetinic acid on cytochrome P450 3A activity[J].Pharmacology, 2010, 86(5/6):287-292.
[43] AKAO T, AKAO T, AOYAMA M, et al. Metabolism of glycyrrhetic acid by rat liver microsomes-III. Male-specific glycyrrhe tinate dehydrogenase[J]. Biochemical Pharmacology, 1990, 40(2):291.
[44]郭建明,段金廒,郝海平,等.基于药物体内代谢过程的中药配伍禁忌研究思路与方法[J].中草药,2011,42(12):2373-2378.
[45] KIM Y W, KANG H E, LEE M G, et al. Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes[J].Am J Physiol Gastrointest Liver Physiol, 2009, 29 6(2):G372-G381.
[46] SEO J Y, LEE Y S, KIM H J, et al. Dehydroglyasperin C iso lated from licorice caused Nrf2-mediated induction of detoxifying enzymes[J]. J Agric Food Chem, 2010, 58(3):1603-1608.
[47] GONG H, LI H D, YAN M, et al. Effect of licorice on the induction of phase II metabolizing enzymes and phase III transporters and its possible mechanism[J]. Die Pharmazie, 2014,69(12):894.
[48] GONG H, ZHANG B K, YAN M, et al. A protective mechanism of licorice(Glycyrrhizauralensis):isoliquiritigenin stimulates detoxification system via Nrf2 activation[J]. Journal of Ethnopharmacology, 2015, 162(24):134-139.
[49] SONG Q, ZHANG A, YAN G, et al. Technological advances in current metabolomics and its application in tradition Chinese medicine[J]. Rsc Advances, 2017,7(84):53516-53524.
[50] SUN B, ZHANG M, ZHANG Q, et al. Metabonomics study of the effects of pretreatment with glycyrrhetinic acid on mesaconitineinduced toxicity in rats[J]. Journal of Ethnopharmacology, 2014,154(3):839-846.
[51]刘建群,王卓,徐金娣,等.甘草干预雷公藤内酯酮的代谢组学分析[J].中国实验方剂学杂志,2016,22(19):70-75.
[52] YU J, JIANG Y S, JIANG Y, et al. Targeted metabolomic study indicating glycyrrhizin’s protection against acetaminopheninduced liver damage through reversing fatty acid metabolism[J].Phytotherapy Research, 2014, 28(6):933-936.
[53] RIZZATO G, SCALABRIN E, RADAELLI M, et al. A new exploration of licorice metabolome[J]. Food Chemistry, 2017, 221(22):959-968.
[54] SIMMLER C, GAUTHIER L, ANDERSON J R, et al. The combination of DNA barcoding and metabolomics for the multiconstituents characterization of Licorice botanicals[J]. Planta Medica, 2015, 81(11):3.
[55]贺小燕.甘草蛋白自组装行为研究[D].福州:福州大学,2013.
[56] CHU H, ZHANG A H, HAN Y, et al. Metabolomics and its potential in drug discovery and development from TCM[J].World Journal of Traditional Chinese Medicine, 2015, 1(4):26-32.
[57] YUAN Y L, XIA X, LI Q W, et al. Study of pharmacodynamic material basis of single-component Chinese medicine based on metabolomics[J]. Curr Res Integr Med, 2015, 1(1):41-44.
[2]郑雪峰,赵运峰.甘草化学成分及药理作用分析[J].中国保健营养,2017,27(10):328-329.
[3]唐进法.马钱子配伍甘草前后汤液中生物碱含量变化[J].航空航天医药,2010,21(8):1529.
[4]杨明,刘小彬,黄庆德.附子甘草配伍减毒增效机理探析[J].时珍国医国药,2003,14(4):197-198.
[5]张来新,陈琦.植根深远的超分子化学[J].化工科技,2018,26(1):63-66.
[6]贺福元,周逸群,邓凯文,等.超分子化学对中医药理论的特殊影响[J].中国中药杂志,2014,39(8):1534-1543.
[7] TIAN Q, WANG X H, WANG W, et al. Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid[J]. Nanomedicine Nanotechnology Biology&Medicine, 2012, 8(6):870-879.
[8] ZHANG J, ZHANG M, JI J, et al. Glycyrrhetinic acid-mediated polymeric drug delivery targeting the acidic microenvironment of hepatocellular carcinoma[J]. Pharmaceutical Research, 2015,32(10):3376-3390.
[9]何乃普,逯盛芳,赵伟刚,等.基于蛋白质分子自组装体系的构建[J].化学进展,2014,26(z1):303-309.
[10] KE L J, GAO G Z, SHEN Y, et al. Encapsulation of aconitine in self-assembled licorice protein nanoparticles reduces the toxicity in vivo[J]. Nanoscale Research Letters, 2015, 10(1):449.
[11] SAKIYA Y, AKADA Y, KAWANO S, et al. Rapid estimation of glycyrrhizin and glycyrrhetinic acid in plasma by high-speed liquid chromatography[J]. Chemical&Pharmaceutical Bulletin,1979, 27(5):1125-1129.
[12]孙成春.HPLC法测定健康志愿者甘草甜素的药动学特征[J].国外医学:药学分册,1993(4):250-251.
[13]李锐,晏亦林,周莉玲,等.四逆汤的药动学研究[J].中成药,2002,24(10):777-780.
[14]黄洁,谭牛仔,贺龙刚,等.甘草与乌头液对小鼠乌头毒量药动学参数的影响[J].湖南中医药大学学报,2007,27(5):53-54.
[15] WANG W, WANG C, GU S, et al. Pharmacokinetic Studies of the Significance of Herbaceous Compatibility of Peony Liquorice Decoction[J]. World Science&Technology, 2009, 11(3):382-387.
[16]张锐,李青,刘芳,等.LC-MS/MS法研究甘草对雷公藤内酯酮药代动力学及组织分布与排泄的影响[J].药物分析杂志,2010,16(9):151-156.
[17]韩刚,康欣,翟冠钰,等.甘草与大黄配伍对大黄酸在大鼠体内药动学的影响[J].中国实验方剂学杂志,2010,16(9):72-74.
[18]章津铭,傅超美,秦素红,等.LC-MS/MS比较研究附子配伍甘草对大鼠体内次乌头碱药动学影响[J].世界科学技术-中医药现代化,2011,13(6):1048-1053.
[19]李菊花,蔡文涛,陈勇,等.拉米夫定与甘草次酸合用的大鼠药动学研究[J].湖北大学学报(自然科学版),2011,33(1):115-118.
[20]漆林艳,黄亮,杨宝春,等.甘草甜素对大鼠体内苦参碱药动学的影响[J].中国药房,2012,23(11):985-986.
[21]王志琪,曾嵘,谭志荣,等.附子与甘草配伍前后乌头碱和甘草次酸在大鼠体内的药动学比较[J].中成药,2012,34(12):2305-2309.
[22] SHI L, TANG X, DANG X, et al. Investigating herb-herb interactions:the potential attenuated toxicity mechanism of the combined use of Glycyrrhizae radix et rhizoma(Gancao)and Sophoraeflavescentis radix(Kushen)[J]. Journal of Ethnopharmacology, 2015, 165(4):243-250.
[23] ZHOU B, ZHANG J, WU S, et al. The influence of compatibility of processed radix AconitiKusnezoffii, on the pharmacokinetic of four components in Glycyrrhizauralensis, Fisch[J]. Journal of Ethnopharmacology, 2015, 169(8):1-7.
[24]杨锐,李金良,王斌,等.甘草提取物对左氧氟沙星在大鼠体内药动学及组织分布的影响[J].中国兽药杂志,2016,50(3):35-38.
[25]卫平,马钦海,任孟月,等.配伍对麻黄甘草药对中麻黄类生物碱在大鼠体内组织分布的影响[J].药学研究,2016,35(4):187-192.
[26] ZHANG M, DENG Y, WANG C, et al. An LC–MS/MS method for determination of bioactive componentsof liquorice and Semen Strychni in rat plasma:Applicationto a pharmacokinetics study[J]. Drug Test Anal, 2018, 10(2):262-271.
[27] SUN S, CHEN Q, GE J, et al. Pharmacokinetic interaction of aconitine, liquiritin and 6-gingerol in a traditional Chinese herbal formula, Sini Decoction[J]. Xenobiotica, 2018, 48(1):1-8.
[28] GU L, WANG X, LIU Z, et al. A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or RhizomaLigustici extract on the comparative toxicokinetics of strychnine and brucine in rats[J].Food&Chemical Toxicology An International Journal Published for the British Industrial Biological Research Association,2014, 68(4):226-233.
[29]王敏,齐云.Caco-2细胞模型及其在药物吸收研究中的应用新进展[J].中国药学杂志,2007,42(16):1201-1204.
[30] VERHALEN B, DASTVAN R, THANGAPANDIAN S, et al. Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein[J]. Nature, 2017, 543(7647):738-741.
[31]彭燕,谭晓斌,贾晓斌.甘草黄酮类成分对Caco-2细胞P-糖蛋白功能和表达的影响[J].中草药,2013,44(19):2703-2709.
[32]何丹,颜苗,李焕德,等.甘草提取物及其主要成分对Caco-2细胞膜上P-gp功能和表达的影响[J].中国药学杂志,2010,45(10):751-755.
[33]叶敏.马钱子碱、次乌头碱的体外吸收机制及其它们分别与甘草苷的转运相互作用研究[D].武汉:湖北大学,2012.
[34] GUENGERICH F P. Cytochrome p450 and chemical toxicology[J].Chemical Research in Toxicology, 2008, 21(1):70-83.
[35] BROWN C M, REISFELD B, MAYENO A N. Cytochromes P450:a structure-based summary of biotransformations using representative substrates[J]. Drug Metabolism Reviews, 2008, 40(1):91-100.
[36]徐硕,徐文峰,金鹏飞,等.甘草对药物代谢酶以及化学药物体内代谢的影响[J].中南药学,2017,15(3):329-334.
[37]刘星雨.甘草水提物对细胞色素P450酶主要亚型的表达影响及其对雷公藤内酯醇的减毒增效作用[D].镇江:江苏大学,2014.
[38]邢盼盼,吴文华,杜鹏,等.马钱子碱与甘草次酸、甘草苷配伍后对大鼠肝脏CYP450的影响[J].药学学报,2011,36(5):573-580.
[39]涂江华.甘草酸对CYP450酶的影响及其机制研究[D].长沙:中南大学,2010.
[40] HYE G J, HO J Y, SUNG J P, et al. Hepatoprotective effects of 18β-glycyrrhe-dnicaeid on carbon tetrachloride-induced liver injury:inhibition of cyt-ochrome P4502E1 expression[J]. Pharnacological Research,2002, 46(3):221-227.
[41]熊月琴.甘草次酸对大鼠肝脏CYP450酶基因表达与蛋白活性的影响[D].武汉:湖北大学,2010.
[42] LI H Y, XU W, SU J, et al. In vitro and in vivo inhibitory effects of glycyrrhetinic acid on cytochrome P450 3A activity[J].Pharmacology, 2010, 86(5/6):287-292.
[43] AKAO T, AKAO T, AOYAMA M, et al. Metabolism of glycyrrhetic acid by rat liver microsomes-III. Male-specific glycyrrhe tinate dehydrogenase[J]. Biochemical Pharmacology, 1990, 40(2):291.
[44]郭建明,段金廒,郝海平,等.基于药物体内代谢过程的中药配伍禁忌研究思路与方法[J].中草药,2011,42(12):2373-2378.
[45] KIM Y W, KANG H E, LEE M G, et al. Liquiritigenin, a flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic transporters and phase-II enzymes[J].Am J Physiol Gastrointest Liver Physiol, 2009, 29 6(2):G372-G381.
[46] SEO J Y, LEE Y S, KIM H J, et al. Dehydroglyasperin C iso lated from licorice caused Nrf2-mediated induction of detoxifying enzymes[J]. J Agric Food Chem, 2010, 58(3):1603-1608.
[47] GONG H, LI H D, YAN M, et al. Effect of licorice on the induction of phase II metabolizing enzymes and phase III transporters and its possible mechanism[J]. Die Pharmazie, 2014,69(12):894.
[48] GONG H, ZHANG B K, YAN M, et al. A protective mechanism of licorice(Glycyrrhizauralensis):isoliquiritigenin stimulates detoxification system via Nrf2 activation[J]. Journal of Ethnopharmacology, 2015, 162(24):134-139.
[49] SONG Q, ZHANG A, YAN G, et al. Technological advances in current metabolomics and its application in tradition Chinese medicine[J]. Rsc Advances, 2017,7(84):53516-53524.
[50] SUN B, ZHANG M, ZHANG Q, et al. Metabonomics study of the effects of pretreatment with glycyrrhetinic acid on mesaconitineinduced toxicity in rats[J]. Journal of Ethnopharmacology, 2014,154(3):839-846.
[51]刘建群,王卓,徐金娣,等.甘草干预雷公藤内酯酮的代谢组学分析[J].中国实验方剂学杂志,2016,22(19):70-75.
[52] YU J, JIANG Y S, JIANG Y, et al. Targeted metabolomic study indicating glycyrrhizin’s protection against acetaminopheninduced liver damage through reversing fatty acid metabolism[J].Phytotherapy Research, 2014, 28(6):933-936.
[53] RIZZATO G, SCALABRIN E, RADAELLI M, et al. A new exploration of licorice metabolome[J]. Food Chemistry, 2017, 221(22):959-968.
[54] SIMMLER C, GAUTHIER L, ANDERSON J R, et al. The combination of DNA barcoding and metabolomics for the multiconstituents characterization of Licorice botanicals[J]. Planta Medica, 2015, 81(11):3.
[55]贺小燕.甘草蛋白自组装行为研究[D].福州:福州大学,2013.
[56] CHU H, ZHANG A H, HAN Y, et al. Metabolomics and its potential in drug discovery and development from TCM[J].World Journal of Traditional Chinese Medicine, 2015, 1(4):26-32.
[57] YUAN Y L, XIA X, LI Q W, et al. Study of pharmacodynamic material basis of single-component Chinese medicine based on metabolomics[J]. Curr Res Integr Med, 2015, 1(1):41-44.