中药作用靶点的预测及发现方法研究进展
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摘要
与单一作用靶点的药物相比较,中药的作用机制为典型的多成分、多靶点、多途径的整体性治疗,各药物之间能够产生协同作用,最终达到增效减毒的目的。确证中药作用的靶点,对阐明我国传统药物的作用机制具有重要的理论价值,也为中药的临床应用提供重要参考。近年来研究表明,对中药多组分作用多靶点的探究主要是通过网络药理学、计算机辅助药物设计、蛋白质组学、生物芯片等途径实现。本文综述了近5年在中药作用靶点预测、识别和确证研究中所采用的主要方法和途径,为进一步阐明中药的作用靶点提供了参考。
Compared to the drug with single target,traditional Chinese medicines( TCM) with the overall therapeutic effect have the typical mechanism such as multi-components,multi-targets and multi-channels. In this system,many compounds together produce a synergistic effect on the purpose of reducing toxicity and improving the therapeutic effect. It is really important for TCM that the molecular mechanism will be clarified and be confirmed. The confirmed targets would provide an important reference for the clinical application of TCM. According to the recently studies,the prediction,identification and validation of the multi-target that TCM acted on are mainly through network pharmacology,computer-aided drug design,pr-oteomics and bioship. By reviewing the literature in five years,this paper would provide a good reference for the methods applying in mechanism studying of TCM.
Compared to the drug with single target,traditional Chinese medicines( TCM) with the overall therapeutic effect have the typical mechanism such as multi-components,multi-targets and multi-channels. In this system,many compounds together produce a synergistic effect on the purpose of reducing toxicity and improving the therapeutic effect. It is really important for TCM that the molecular mechanism will be clarified and be confirmed. The confirmed targets would provide an important reference for the clinical application of TCM. According to the recently studies,the prediction,identification and validation of the multi-target that TCM acted on are mainly through network pharmacology,computer-aided drug design,pr-oteomics and bioship. By reviewing the literature in five years,this paper would provide a good reference for the methods applying in mechanism studying of TCM.
引文
[1]刘丽宁.临床用药优势之一多靶点探讨[J].时珍国医国药,2010,(3):745-746.
[2]Yan J.,Wang Y.,Luo S.J.,et al.TCM grammar systems:an approach to aid the interpretation of the molecular interactions in Chinese herbal medicine[J].Journal of Ethnopharmacol,2011,137(1):77-84.
[3]佟雷,高月娟,刘金丽.从传统中药向中药现代化迈进过程中的若干问题探究[J].微量元素与健康研究,2013,(3):27-28.
[4]Li S.,Zhang B.Traditional Chinese medicine network pharmacology:theory,methodology and application[J].Chinese Journal of Natural Medicines,2013,11(2):110-120.
[5]吴磊宏,高秀梅,王林丽,等.附子多成分作用靶点预测及网络药理学研究[J].中国中药杂志,2011,36(21):2907-2910.
[6]宋阔魁,毕天,展晓日,等.网络药理学指导下的中药有效成分发现策略[J].世界科学技术-中医药现代化,2014,(1):27-31.
[7]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[8]李翔,吴磊宏,范骁辉,等.复方丹参方主要活性成分网络药理学研究[J].中国中药杂志,2011,36(21):2911-2915.
[9]Tao W.Y,Xu X.,Wang X.,et al.Network pharmacologybased prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease[J].Journal of Ethnopharmacology,2013,145(1):1-10.
[10]Li B.H.,Tao W.Y.,Zheng C.L.,et al.Systems pharmacology-based approach for dissecting the addition and subtraction theory of traditional Chinese medicine:An example using Xiao-Chaihu-Decoction and Da-Chaihu-Decoction[J].Computers in Biology and Medicine,2014,53(2):19-29.
[11]孙冬梅,陈玉兴,曾晓会,等.基于系统生物学的计算机辅助药物设计中药研发新模式[J].中国实验方剂学杂志,2014,20(17):223-227.
[12]Tsai T.Y.,Chang K.W.,Chen C.Y..i Screen:world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan[J].Journal of computer-aided molecular design,2011,25(6):525-531.
[13]任洁,魏静.分子对接技术在中药研究中的应用[J].中国中医药信息杂志,2014,(1):123-125.
[14]Chang T.T.,Sun M.F.,Wong Y.H.,et al.Drug design for m PGES-1 from traditional Chinese medicine database:A screening,docking,QSAR,m-olecular dynamics,and pharmacophore mapping study[J].Journal of the Taiwan Institute of Chemical Engineers,2011,42(4):580-591.
[15]罗丽萍,余小平,韩彬,等.花青素主要成分与HER-2激酶区的分子对接[J].生物工程学报,2014,30(3):504-513.
[16]潘婷婷,周植星,韩英梅,等.基于植物成分的蛋白酶激活受体1拮抗剂的虚拟筛选和实验筛选[J].中草药,2014,45(10):1427-1433.
[17]刘美凤,蒋利荣,刘华鼐,等.番石榴叶抗Ⅱ型糖尿病活性成分的虚拟筛选[J].华南理工大学学报:自然科学版,2011,39(3):28-31.
[18]陈少军,陈宏降,郭章华.反向分子对接法预测丹参醇A的潜在靶点[J].中药药理与临床,2014,30(5):58-61.
[19]陈少军,陈宏降,郭章华.茯苓酸潜在靶点预测研究[J].中药药理与临床,2013,29(4):67-70.
[20]王星,张燕玲,王耘,等.TRPV1离子通道与中药辛味药性的关系研究[J].中国中药杂志,2014,39(13):2422-2427.
[21]杨红芹,李学军.化学蛋白质组学与药物靶点的发现[J].药学学报,2011,46(8):877-882.
[22]张丽军,贾小芳,尹林,等.蛋白质组学方法研究唐草片对微粒体CYP450酶的影响[J].中国中药杂志,2014,39(11):2136-2139.
[23]姚辛敏,王琪,谢宁,等.地黄饮子含药脑脊液对AD细胞模型影响的差异蛋白质组学研究[J].中医药学报,2014,42(4):49-52.
[24]戎志斌,李映红,许蕴,等.柴胡疏肝散含药血清蛋白质组学的初步研究[J].世界中西医结合杂志,2013,9(3):283-286.
[25]Sun H.,Zhang A.,Yan G.,et al.Proteomics study on the hepatoprotectiv-e effects of traditional Chinese medicine formulae Yin-Chen-Hao-Tang by a co-mbination of two-dimensional polyacrylamide gel electrophoresis and matrix-ass-isted laser desorption/ionization-time of flight mass spectrometry[J].Journal ofpharmaceutical and biomedical analysis,2013,75(2):173-179.
[26]Firouzi Z.,Lari P.,Rashedinia M.,et al.Proteomics screening of molecul-ar targets of curcumin in mouse brain[J].Life sciences,2014,98(1):12-17.
[27]Lao Y.,Wang X.,Xu N.,et al.Application of proteomics to determine t-he mechanism of action of traditional Chinese medicine remedies[J].J Ethno-pharmacol,2014,155(1):1-8.
[28]黄春洪,孔毅,段涛,等.蛋白质组学技术与药物作用新靶点研究进展[J].中国药学杂志,2005,(8):564-567.
[29]李书文,张爱芹,曾鸣,等.生物芯片技术在中医药研究中的应用[J].时珍国医国药,2013,24(10):2489-2492.
[30]李英博,赵香琴,姜英虹,等.基因芯片技术筛选人参皂苷Rg1促进人神经干细胞增殖的分子靶点研究[J].中国中药杂志,2013,38(16):2701-2705.
[31]玄毅,刘君,赵坤生.SELDI蛋白芯片技术在筛选中草药靶点中的应用[J].社区医学杂志,2009,7(23):63-64.
[32]Stoll D,Bachmann J,Templin M F,et al.Microarray technology:an increasing variety of screening tools for proteomic research[J].Drug Discovery Today:TARGETS,2004,3(1):24-31.
[32]刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,(6):696-703.
[33]汤佩佩,白明,苗明三.中医药研究与网络药理学[J].中医学报,2012,(9):1112-1115.
[34]刘艾林,杜冠华.网络药理学:药物发现的新思想[J].药学学报,2010,(12):1472-1477.
[35]刘幸,周虎.蛋白质组学技术在网络药理学中的应用[J].药学进展,2014,38(2):89-96.
[36]刘庆山,张梓倩,方亮,等.高通量技术与网络药理学在中药活性成分筛选中的应用[J].中国中药杂志,2012,37(2):134-137.
[37]Gu J.Y.,Zhang H.,Chen L.R.,et al.Drug-target network and polypharmacology studies of a Traditional Chinese Medicine for typeⅡdiabetes mellitus[J].Computational Biology and Chemistry,2011,35(5):293-297.
[38]Chen L,Du J,Dai Q,et al.Prediction of anti-tumor chemical probes of a traditional Chinese medicine formula by HPLC fingerprinting combined with molecular docking[J].European journal of medicinal chemistry,2014,83(2):294-306.
[39]丁俊杰,丁晓琴,李大禹,等.ω-芋螺毒素的定量构效关系与虚拟筛选[J].物理化学学报,2014,30(11):2157-2167.
[40]孟志昌,周雪忠,雷蕾,等.基于计算的中药靶点预测研究探讨与实验分析[J].世界科学技术-中医药现代化,2014,(11):2296-2303.
[2]Yan J.,Wang Y.,Luo S.J.,et al.TCM grammar systems:an approach to aid the interpretation of the molecular interactions in Chinese herbal medicine[J].Journal of Ethnopharmacol,2011,137(1):77-84.
[3]佟雷,高月娟,刘金丽.从传统中药向中药现代化迈进过程中的若干问题探究[J].微量元素与健康研究,2013,(3):27-28.
[4]Li S.,Zhang B.Traditional Chinese medicine network pharmacology:theory,methodology and application[J].Chinese Journal of Natural Medicines,2013,11(2):110-120.
[5]吴磊宏,高秀梅,王林丽,等.附子多成分作用靶点预测及网络药理学研究[J].中国中药杂志,2011,36(21):2907-2910.
[6]宋阔魁,毕天,展晓日,等.网络药理学指导下的中药有效成分发现策略[J].世界科学技术-中医药现代化,2014,(1):27-31.
[7]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[8]李翔,吴磊宏,范骁辉,等.复方丹参方主要活性成分网络药理学研究[J].中国中药杂志,2011,36(21):2911-2915.
[9]Tao W.Y,Xu X.,Wang X.,et al.Network pharmacologybased prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease[J].Journal of Ethnopharmacology,2013,145(1):1-10.
[10]Li B.H.,Tao W.Y.,Zheng C.L.,et al.Systems pharmacology-based approach for dissecting the addition and subtraction theory of traditional Chinese medicine:An example using Xiao-Chaihu-Decoction and Da-Chaihu-Decoction[J].Computers in Biology and Medicine,2014,53(2):19-29.
[11]孙冬梅,陈玉兴,曾晓会,等.基于系统生物学的计算机辅助药物设计中药研发新模式[J].中国实验方剂学杂志,2014,20(17):223-227.
[12]Tsai T.Y.,Chang K.W.,Chen C.Y..i Screen:world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan[J].Journal of computer-aided molecular design,2011,25(6):525-531.
[13]任洁,魏静.分子对接技术在中药研究中的应用[J].中国中医药信息杂志,2014,(1):123-125.
[14]Chang T.T.,Sun M.F.,Wong Y.H.,et al.Drug design for m PGES-1 from traditional Chinese medicine database:A screening,docking,QSAR,m-olecular dynamics,and pharmacophore mapping study[J].Journal of the Taiwan Institute of Chemical Engineers,2011,42(4):580-591.
[15]罗丽萍,余小平,韩彬,等.花青素主要成分与HER-2激酶区的分子对接[J].生物工程学报,2014,30(3):504-513.
[16]潘婷婷,周植星,韩英梅,等.基于植物成分的蛋白酶激活受体1拮抗剂的虚拟筛选和实验筛选[J].中草药,2014,45(10):1427-1433.
[17]刘美凤,蒋利荣,刘华鼐,等.番石榴叶抗Ⅱ型糖尿病活性成分的虚拟筛选[J].华南理工大学学报:自然科学版,2011,39(3):28-31.
[18]陈少军,陈宏降,郭章华.反向分子对接法预测丹参醇A的潜在靶点[J].中药药理与临床,2014,30(5):58-61.
[19]陈少军,陈宏降,郭章华.茯苓酸潜在靶点预测研究[J].中药药理与临床,2013,29(4):67-70.
[20]王星,张燕玲,王耘,等.TRPV1离子通道与中药辛味药性的关系研究[J].中国中药杂志,2014,39(13):2422-2427.
[21]杨红芹,李学军.化学蛋白质组学与药物靶点的发现[J].药学学报,2011,46(8):877-882.
[22]张丽军,贾小芳,尹林,等.蛋白质组学方法研究唐草片对微粒体CYP450酶的影响[J].中国中药杂志,2014,39(11):2136-2139.
[23]姚辛敏,王琪,谢宁,等.地黄饮子含药脑脊液对AD细胞模型影响的差异蛋白质组学研究[J].中医药学报,2014,42(4):49-52.
[24]戎志斌,李映红,许蕴,等.柴胡疏肝散含药血清蛋白质组学的初步研究[J].世界中西医结合杂志,2013,9(3):283-286.
[25]Sun H.,Zhang A.,Yan G.,et al.Proteomics study on the hepatoprotectiv-e effects of traditional Chinese medicine formulae Yin-Chen-Hao-Tang by a co-mbination of two-dimensional polyacrylamide gel electrophoresis and matrix-ass-isted laser desorption/ionization-time of flight mass spectrometry[J].Journal ofpharmaceutical and biomedical analysis,2013,75(2):173-179.
[26]Firouzi Z.,Lari P.,Rashedinia M.,et al.Proteomics screening of molecul-ar targets of curcumin in mouse brain[J].Life sciences,2014,98(1):12-17.
[27]Lao Y.,Wang X.,Xu N.,et al.Application of proteomics to determine t-he mechanism of action of traditional Chinese medicine remedies[J].J Ethno-pharmacol,2014,155(1):1-8.
[28]黄春洪,孔毅,段涛,等.蛋白质组学技术与药物作用新靶点研究进展[J].中国药学杂志,2005,(8):564-567.
[29]李书文,张爱芹,曾鸣,等.生物芯片技术在中医药研究中的应用[J].时珍国医国药,2013,24(10):2489-2492.
[30]李英博,赵香琴,姜英虹,等.基因芯片技术筛选人参皂苷Rg1促进人神经干细胞增殖的分子靶点研究[J].中国中药杂志,2013,38(16):2701-2705.
[31]玄毅,刘君,赵坤生.SELDI蛋白芯片技术在筛选中草药靶点中的应用[J].社区医学杂志,2009,7(23):63-64.
[32]Stoll D,Bachmann J,Templin M F,et al.Microarray technology:an increasing variety of screening tools for proteomic research[J].Drug Discovery Today:TARGETS,2004,3(1):24-31.
[32]刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,(6):696-703.
[33]汤佩佩,白明,苗明三.中医药研究与网络药理学[J].中医学报,2012,(9):1112-1115.
[34]刘艾林,杜冠华.网络药理学:药物发现的新思想[J].药学学报,2010,(12):1472-1477.
[35]刘幸,周虎.蛋白质组学技术在网络药理学中的应用[J].药学进展,2014,38(2):89-96.
[36]刘庆山,张梓倩,方亮,等.高通量技术与网络药理学在中药活性成分筛选中的应用[J].中国中药杂志,2012,37(2):134-137.
[37]Gu J.Y.,Zhang H.,Chen L.R.,et al.Drug-target network and polypharmacology studies of a Traditional Chinese Medicine for typeⅡdiabetes mellitus[J].Computational Biology and Chemistry,2011,35(5):293-297.
[38]Chen L,Du J,Dai Q,et al.Prediction of anti-tumor chemical probes of a traditional Chinese medicine formula by HPLC fingerprinting combined with molecular docking[J].European journal of medicinal chemistry,2014,83(2):294-306.
[39]丁俊杰,丁晓琴,李大禹,等.ω-芋螺毒素的定量构效关系与虚拟筛选[J].物理化学学报,2014,30(11):2157-2167.
[40]孟志昌,周雪忠,雷蕾,等.基于计算的中药靶点预测研究探讨与实验分析[J].世界科学技术-中医药现代化,2014,(11):2296-2303.