基于线粒体的中药物质基础研究科研方法应用进展
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摘要
概述了中药物质基础研究现状、以线粒体为靶点中药物质基础研究的主要科研方法及应用进展。以线粒体为靶点中药物质基础研究的主要科研方法及应用包括:基于线粒体的离心超滤/液质联用方法筛选以线粒体为靶点的中药活性成分、基于线粒体的荧光成像分析技术筛选中药活性物质、中药药效物质筛选结合靶标分析、基于线粒体能量代谢研究中药有效物质。为以线粒体为靶点中药物质基础研究提供参考依据,并对现存方法存在的问题有所阐释。参考文献49篇。
引文
[1]林飞,王阶,郭丽丽,等.中药细胞内作用靶点---线粒体[J].世界科学技术-中医药现代化,2015,17(3):422-426.
[2]杨兴鑫,徐风,俞捷,等.中药对线粒体功能的影响及其药理作用研究进展[J].生命科学仪器,2017,15(4):15-21.
[3]杨子平,包怡敏.三七总皂苷对线粒体调控作用的研究进展[J].中国中药杂志,2017,42(5):870-874.
[4]JIA L,MA S,HOU X,et al.The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment[J].Oncol Lett,2013,5(5):1439-1447.
[5]MU X,ZHANG Y,LI J,et al.Angelica sinensis polysaccharide prevents hematopoietic stem cells senescence in D-galactose-induced aging mouse model[J].Stem Cells Int,2017,2017(3):3508907.
[6]SURESH S,PRITHIVIRAJ E,LAKSHMIN V,et al.Effect of Mucuna pruriens(Linn.)on mitochondrial dysfunction and DNA damage in epididyma sperm of streptozotocin induced diabetic rat[J].J Ethnopharmacol,2013,145(1):32-41.
[7]OCLOO A,DONGDEM J T.Mitochondria as pharmacological targets:the discovery of novel anti-obesity mitochondrial uncouplers from Africa’s medicinal plants[J].Afr J Tradit Complement Altern Med,2011,9(2):256-259.
[8]YANG X,YAO W,LIU H,et al.Tangluoning,a traditional Chinese medicine,attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway[J].Scientific Reports,2017,7(1):1014.
[9]KHAN M A,SINGLY M,KHAN M S.et al.Alternative approach for mitigation of doxorubicin-induced cardiotoxicity using herbal agents[J].Curr Clin Pharmacol,2014,9(3):288-297.
[10]ZHAO Q,PENG Y,HUANG K,et al.Salvianolate protects hepatocytes from oxidative stress by attenuating mitochondrial injury[J].Evidence-based Complementary and Alternative Medicine,2016,2016(4):1-10.
[11]齐炼文,周建良,赫海平,等.基于中医药特点的中药体内外药效物质组生物/化学集成表征新方法[J].中国药科大学学报,2010,41(3):195-202.
[12]肖平,李祥,陈建伟,等.中药药效物质基础研究思路与方法概述[J].时珍国医国药,2014,25(8):1935-1938.
[13]YAN Y,CHAI C Z,WANG D W,et al.HPLC-DAD-Q-TOF-MS/MS analysis and HPLC quantitation of chemical constituents in traditional Chinese medicinal formula Ge-Gen decoction[J].J Pharm Biomed Anal,2013,80(3):192-202.
[14]XUE C,JIANG S,GUO J,et al.Screening for in vitro metabolites of Abelmoschus manihot extract in intestinal bacteria by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry[J].J Chromatogr B,2011,879(32):3901-3908.
[15]XIONG Y K,LIN X,LIANG S,et al.Identification of senkyunolide I metabolites in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry[J].J Pharm Biomed Anal,2013,81-82(6):178-186.
[16]CHENG XL,WEI F,XIAO XY,et al.Identification of five gelatins by ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/Q-TOF-MS)using principal component analysis[J].J Pharm Biomed Anal,2012,62(2):191-195.
[17]龙建纲,汪振诚,王学敏.线粒体:新的细胞内药物作用靶点[J].中国药理学通报,2003,19(8):859-863.
[18]ZHANG Y,PENG M J,LIU L,et al.Screening,identification,andpotential interaction of active compounds from Eucommia ulmodies leavesbinding with bovine serum albumin[J].J Agric Food Chem,2012,60(12):3119-3125.
[19]ZHANG X,ZHANG S,ZHU S,et al.Identification of mitochondria-targeting anticancer compounds by an in vitrostrategy[J].Anal Chem,2014,86(11):5232-5237.
[20]MONTAGUE CR,FITZMAURICE A,HOVER BM,et al.Screen for small molecules increasing the mitochondrial membrane potential[J].J Biomol Screen,2014,19(3):387-398.
[21]TSIPER M V,STURGIS J,AVRAMOVA L V,et al.Differential mitochondrial toxicity screening and multi-parametric data analysis[J].PLoS One,2012,7(10):e45226.
[22]MUNIGUNTI R,MULABAGAL V,CALDERON AI.Screening of natural compounds forligands to PfTrxR by ultrafiltration and LC-MS based binding assay[J].J Pharm Biomed Anal,2011,55(2):265-271.
[23]ZHOU H,XING JP,LIU S,et al.Screening and determination for potential a-glucosidase inhibitors from leaves of Acanthopanax senticosus harms by using UF-LC/MSand ESI-MS(n)[J].Phytochem Anal,2012,23(4):315-323.
[24]CHOI Y,JERMIHOV K,NAM SJ,et al.Screening natural products for inhibitors of quinone reductase-2 using ultrafiltration LC-MS[J].Anal Chem,2011,83(3):1048-1052.
[25]PASCALI J P,FAIS P,VAIANO F,et al.Application of HRAM screening and LC-MS/MS confirmation of active pharmaceutical ingredient in“natural”herbal supplements[J].Forensic Science International,2018,286(5):e28-e31.
[26]YANG X X,XU F,WANG D,et al.Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes:herbal medicines as a case study[J].Journal of Chromatogryaph A,2015,1413:33-46.
[27]WATTANAPITAYAKUL S K,CHULAROJMONTRI L,HERUNSALEE A,et al.Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity[J].Basic Clin Pharmacol Toxicol,2005,96(1):80-87.
[28]STEPHENS D J,ALLAN V J.Light microscopy techniques for live cell imaging[J].Science,2003,300(5616):82-86.
[29]LIEBEL U,STARKUVIENE V,ERFLE H,et al.A microscope-based screening platform for large-scale functional protein analysis in intact cells[J].FEBS Lett,2003,554(3):394-398.
[30]NGUYEN A H,NGUYEN V T,KAMIO Y,et al.Singlemolecule visualization of environment-sensitive fluorophores inserted into cell membranes by staphylococcal gamma-hemolysin[J].Biochemistry,2006,45(8):2570-2576.
[31]SEISENBERGER G,RIED M U,ENDRESS T,et al.Realtime single-molecule imaging of the infection pathway of an adeno-associated virus[J].Science,2001,294(5548):1929-1932.
[32]MORGAN A G,MCCAULEY T J,STANAITIS M L,et al.Development and validation of a fluorescence technology for both primary and secondary screening of kinases that facilitates compound selectivity and site-specific inhibitor determination[J].Assay Drug Dev Technol,2004,2(2):171-181.
[33]DAI G H,LIU N,ZHU J W,et al.Qishen Yiqi dripping pills promote angiogenesis of ischemic cardiac microvascular endothelial cells by regulating microRNA-223-3p expression[J].Evidence-Based Complementary and Alternative Medicine,2016,2016:1-14.
[34]WANG Y,ZHAO X,GAO X,et al.Development of uorescence imaging-based assay for screening cardioprotective compounds from medicinal plants[J].J Analytica Chimica Acta,2011,702(1):87-94.
[35]王月华,贺晓丽,李晓秀,等.小续命汤有效成分组对慢性脑缺血大鼠脑线粒体的保护作用[J].中西医结合学报,2012,10(5):569-576.
[36]YAN W H,LIU J Z.Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro[J].Neural Regen Res,2012,7(27):2099-2106.
[37]MODICA-NAPOLITANO J S,APRILLE J R.Basis for the selective cytotoxicity of rhodamine 123[J].Cancer Res,1987,47(16):4361-4365.
[38]EMAUS R K,GRUNWALD R,LEMASTERS J J.Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria:spectral and metabolic properties[J].Biochim Biophys Acta,1986,850(3):436-448.
[39]杜冠华.中药复方有效成分组学研究[J].中成药,2002,24(11):878.
[40]王月华,秦海林,贺晓丽,等.中药复方小续命汤组分活性评价及抗脑缺血有效成分组制备[J].中国中药杂志,2011,36(15):2140-2144.
[41]YANG S,ZHAO Q,XIANG H,et al.Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on humancancer cells[J].Cancer Cell International,2013,13(1):12.
[42]舒泽柳,曾克武,马晓丽,等.保元汤中具有心肌保护作用的活性成分及其潜在作用靶点研究[J].中国中药杂志,2016,41(5):922-927.
[43]张翠英,郭丽丽,王阶.原儿茶醛的药理研究进展[J].中国实验方剂学杂志,2013,19(23):338.
[44]GAO Y,WANG N,ZHANG Y,et al.Mechanism of protective effects of Danshen against iron overload-induced injury in mice[J].J Ethnopharmcol,2013,145(1):254.
[45]LI F,FAN X,ZHANG Y,et al.Cardioprotection by combination of three compounds from shengmai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission[J].Scientific Reports,2016,6:37114.
[46]王艳艳,孙雪,裴晓蕾,等.中药寒热药性与线粒体能量代谢关系研究[J].中医药信息,2013,30(4):48-55.
[47]李姿,韩慧,杨幼新,等.旋覆代赭汤对RE模型大鼠食管组织线粒体超微结构及SDH活性的影响[J].中国中西医结合消化杂志,2016,24(7):499-503.
[48]石磊,杨鹏,郭舜,等.二陈汤对非酒精性脂肪肝CYP2E1及线粒体能量代谢的影响[J].中国药师,2017,20(2):205-207.
[49]许朝龙,邬善敏,苗志钊,等.小檗碱对梗阻性黄疸大鼠肝细胞线粒体能量代谢的保护作用[J].武汉大学学报(医学版),2016,37(2):183-186.
[2]杨兴鑫,徐风,俞捷,等.中药对线粒体功能的影响及其药理作用研究进展[J].生命科学仪器,2017,15(4):15-21.
[3]杨子平,包怡敏.三七总皂苷对线粒体调控作用的研究进展[J].中国中药杂志,2017,42(5):870-874.
[4]JIA L,MA S,HOU X,et al.The synergistic effects of traditional Chinese herbs and radiotherapy for cancer treatment[J].Oncol Lett,2013,5(5):1439-1447.
[5]MU X,ZHANG Y,LI J,et al.Angelica sinensis polysaccharide prevents hematopoietic stem cells senescence in D-galactose-induced aging mouse model[J].Stem Cells Int,2017,2017(3):3508907.
[6]SURESH S,PRITHIVIRAJ E,LAKSHMIN V,et al.Effect of Mucuna pruriens(Linn.)on mitochondrial dysfunction and DNA damage in epididyma sperm of streptozotocin induced diabetic rat[J].J Ethnopharmacol,2013,145(1):32-41.
[7]OCLOO A,DONGDEM J T.Mitochondria as pharmacological targets:the discovery of novel anti-obesity mitochondrial uncouplers from Africa’s medicinal plants[J].Afr J Tradit Complement Altern Med,2011,9(2):256-259.
[8]YANG X,YAO W,LIU H,et al.Tangluoning,a traditional Chinese medicine,attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway[J].Scientific Reports,2017,7(1):1014.
[9]KHAN M A,SINGLY M,KHAN M S.et al.Alternative approach for mitigation of doxorubicin-induced cardiotoxicity using herbal agents[J].Curr Clin Pharmacol,2014,9(3):288-297.
[10]ZHAO Q,PENG Y,HUANG K,et al.Salvianolate protects hepatocytes from oxidative stress by attenuating mitochondrial injury[J].Evidence-based Complementary and Alternative Medicine,2016,2016(4):1-10.
[11]齐炼文,周建良,赫海平,等.基于中医药特点的中药体内外药效物质组生物/化学集成表征新方法[J].中国药科大学学报,2010,41(3):195-202.
[12]肖平,李祥,陈建伟,等.中药药效物质基础研究思路与方法概述[J].时珍国医国药,2014,25(8):1935-1938.
[13]YAN Y,CHAI C Z,WANG D W,et al.HPLC-DAD-Q-TOF-MS/MS analysis and HPLC quantitation of chemical constituents in traditional Chinese medicinal formula Ge-Gen decoction[J].J Pharm Biomed Anal,2013,80(3):192-202.
[14]XUE C,JIANG S,GUO J,et al.Screening for in vitro metabolites of Abelmoschus manihot extract in intestinal bacteria by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry[J].J Chromatogr B,2011,879(32):3901-3908.
[15]XIONG Y K,LIN X,LIANG S,et al.Identification of senkyunolide I metabolites in rats using ultra performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry[J].J Pharm Biomed Anal,2013,81-82(6):178-186.
[16]CHENG XL,WEI F,XIAO XY,et al.Identification of five gelatins by ultra performance liquid chromatography/time-of-flight mass spectrometry(UPLC/Q-TOF-MS)using principal component analysis[J].J Pharm Biomed Anal,2012,62(2):191-195.
[17]龙建纲,汪振诚,王学敏.线粒体:新的细胞内药物作用靶点[J].中国药理学通报,2003,19(8):859-863.
[18]ZHANG Y,PENG M J,LIU L,et al.Screening,identification,andpotential interaction of active compounds from Eucommia ulmodies leavesbinding with bovine serum albumin[J].J Agric Food Chem,2012,60(12):3119-3125.
[19]ZHANG X,ZHANG S,ZHU S,et al.Identification of mitochondria-targeting anticancer compounds by an in vitrostrategy[J].Anal Chem,2014,86(11):5232-5237.
[20]MONTAGUE CR,FITZMAURICE A,HOVER BM,et al.Screen for small molecules increasing the mitochondrial membrane potential[J].J Biomol Screen,2014,19(3):387-398.
[21]TSIPER M V,STURGIS J,AVRAMOVA L V,et al.Differential mitochondrial toxicity screening and multi-parametric data analysis[J].PLoS One,2012,7(10):e45226.
[22]MUNIGUNTI R,MULABAGAL V,CALDERON AI.Screening of natural compounds forligands to PfTrxR by ultrafiltration and LC-MS based binding assay[J].J Pharm Biomed Anal,2011,55(2):265-271.
[23]ZHOU H,XING JP,LIU S,et al.Screening and determination for potential a-glucosidase inhibitors from leaves of Acanthopanax senticosus harms by using UF-LC/MSand ESI-MS(n)[J].Phytochem Anal,2012,23(4):315-323.
[24]CHOI Y,JERMIHOV K,NAM SJ,et al.Screening natural products for inhibitors of quinone reductase-2 using ultrafiltration LC-MS[J].Anal Chem,2011,83(3):1048-1052.
[25]PASCALI J P,FAIS P,VAIANO F,et al.Application of HRAM screening and LC-MS/MS confirmation of active pharmaceutical ingredient in“natural”herbal supplements[J].Forensic Science International,2018,286(5):e28-e31.
[26]YANG X X,XU F,WANG D,et al.Development of a mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method for screening mitochondria-targeted bioactive constituents from complex matrixes:herbal medicines as a case study[J].Journal of Chromatogryaph A,2015,1413:33-46.
[27]WATTANAPITAYAKUL S K,CHULAROJMONTRI L,HERUNSALEE A,et al.Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity[J].Basic Clin Pharmacol Toxicol,2005,96(1):80-87.
[28]STEPHENS D J,ALLAN V J.Light microscopy techniques for live cell imaging[J].Science,2003,300(5616):82-86.
[29]LIEBEL U,STARKUVIENE V,ERFLE H,et al.A microscope-based screening platform for large-scale functional protein analysis in intact cells[J].FEBS Lett,2003,554(3):394-398.
[30]NGUYEN A H,NGUYEN V T,KAMIO Y,et al.Singlemolecule visualization of environment-sensitive fluorophores inserted into cell membranes by staphylococcal gamma-hemolysin[J].Biochemistry,2006,45(8):2570-2576.
[31]SEISENBERGER G,RIED M U,ENDRESS T,et al.Realtime single-molecule imaging of the infection pathway of an adeno-associated virus[J].Science,2001,294(5548):1929-1932.
[32]MORGAN A G,MCCAULEY T J,STANAITIS M L,et al.Development and validation of a fluorescence technology for both primary and secondary screening of kinases that facilitates compound selectivity and site-specific inhibitor determination[J].Assay Drug Dev Technol,2004,2(2):171-181.
[33]DAI G H,LIU N,ZHU J W,et al.Qishen Yiqi dripping pills promote angiogenesis of ischemic cardiac microvascular endothelial cells by regulating microRNA-223-3p expression[J].Evidence-Based Complementary and Alternative Medicine,2016,2016:1-14.
[34]WANG Y,ZHAO X,GAO X,et al.Development of uorescence imaging-based assay for screening cardioprotective compounds from medicinal plants[J].J Analytica Chimica Acta,2011,702(1):87-94.
[35]王月华,贺晓丽,李晓秀,等.小续命汤有效成分组对慢性脑缺血大鼠脑线粒体的保护作用[J].中西医结合学报,2012,10(5):569-576.
[36]YAN W H,LIU J Z.Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro[J].Neural Regen Res,2012,7(27):2099-2106.
[37]MODICA-NAPOLITANO J S,APRILLE J R.Basis for the selective cytotoxicity of rhodamine 123[J].Cancer Res,1987,47(16):4361-4365.
[38]EMAUS R K,GRUNWALD R,LEMASTERS J J.Rhodamine 123 as a probe of transmembrane potential in isolated rat-liver mitochondria:spectral and metabolic properties[J].Biochim Biophys Acta,1986,850(3):436-448.
[39]杜冠华.中药复方有效成分组学研究[J].中成药,2002,24(11):878.
[40]王月华,秦海林,贺晓丽,等.中药复方小续命汤组分活性评价及抗脑缺血有效成分组制备[J].中国中药杂志,2011,36(15):2140-2144.
[41]YANG S,ZHAO Q,XIANG H,et al.Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on humancancer cells[J].Cancer Cell International,2013,13(1):12.
[42]舒泽柳,曾克武,马晓丽,等.保元汤中具有心肌保护作用的活性成分及其潜在作用靶点研究[J].中国中药杂志,2016,41(5):922-927.
[43]张翠英,郭丽丽,王阶.原儿茶醛的药理研究进展[J].中国实验方剂学杂志,2013,19(23):338.
[44]GAO Y,WANG N,ZHANG Y,et al.Mechanism of protective effects of Danshen against iron overload-induced injury in mice[J].J Ethnopharmcol,2013,145(1):254.
[45]LI F,FAN X,ZHANG Y,et al.Cardioprotection by combination of three compounds from shengmai preparations in mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated mitochondrial fission[J].Scientific Reports,2016,6:37114.
[46]王艳艳,孙雪,裴晓蕾,等.中药寒热药性与线粒体能量代谢关系研究[J].中医药信息,2013,30(4):48-55.
[47]李姿,韩慧,杨幼新,等.旋覆代赭汤对RE模型大鼠食管组织线粒体超微结构及SDH活性的影响[J].中国中西医结合消化杂志,2016,24(7):499-503.
[48]石磊,杨鹏,郭舜,等.二陈汤对非酒精性脂肪肝CYP2E1及线粒体能量代谢的影响[J].中国药师,2017,20(2):205-207.
[49]许朝龙,邬善敏,苗志钊,等.小檗碱对梗阻性黄疸大鼠肝细胞线粒体能量代谢的保护作用[J].武汉大学学报(医学版),2016,37(2):183-186.