中药作用靶点方法学研究进展
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摘要
靶点(drug target)是药物作用的源头,是药物治疗疾病最直接、最重要、最初始的生物学基础.长期以来,中药由于其自身成分复杂的特点,关于作用靶点的揭示与阐明,以及分子药理机制等相关研究一直未能获得突破性进展,因此严重制约了中药的现代化和国际化进程.但是近年来,随着分子生物学、化学生物学以及生物物理学等前沿学科的发展,人们不断摸索和建立了一系列药物靶点的鉴定和识别方法,并尝试将这些方法应用于中药活性成分以及中药复方的作用靶点研究中,且取得了不少原创性成果,极大地推动了中医药的前进步伐.本文总结了近年来在中药靶点研究中出现的新方法与新策略,希望能够对从事中药现代化研究的人们提供全新思路,并拓展新的研究方向,最终促进中医药现代科学研究取得更大的突破.
As an original source of pharmacological actions, drug target is the most direct, important and primary biological basis for drug effects. For a long time, no dramatic breakthroughs have been achieved on traditional Chinese medicine(TCM) target identification and clarification, as well as potential molecular mechanism exploration because of the complicated components, leading to a huge obstruction on the progress of TCM modernization and internationalization. However, with the development of molecular biology, chemical biology and biophysics,researchers have established a series of methods for drug target identification for TCM, and tried to apply these methods to the target identification for TCM active ingredients and prescriptions, resulting in many innovative findings and promoting the development of TCM. Thus, this review summarizes the recent progress on TCM target identification, and hopes to provide a new idea to expand new research direction for the breakthrough progress of TCM study.
As an original source of pharmacological actions, drug target is the most direct, important and primary biological basis for drug effects. For a long time, no dramatic breakthroughs have been achieved on traditional Chinese medicine(TCM) target identification and clarification, as well as potential molecular mechanism exploration because of the complicated components, leading to a huge obstruction on the progress of TCM modernization and internationalization. However, with the development of molecular biology, chemical biology and biophysics,researchers have established a series of methods for drug target identification for TCM, and tried to apply these methods to the target identification for TCM active ingredients and prescriptions, resulting in many innovative findings and promoting the development of TCM. Thus, this review summarizes the recent progress on TCM target identification, and hopes to provide a new idea to expand new research direction for the breakthrough progress of TCM study.
引文
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56 Ma S,Feng C,Zhang X,Dai G,Li C,Cheng X,Liu P,Ju W,Yu H.Complement Ther Med,2013,21:35-41
2 Lin AX,Chan G,Hu Y,Ouyang D,Ung COL,Shi L,Hu H.Chin Med,2018,13:9
3 Guo DA.Pharm Biol,2012,50:663-663
4 Liao SJ.Conn Med,1980,44:381-383
5 Shen YC,Chiou WF,Wang GJ,Chou CJ,Chen CF.Orien Foods Herb,2003,859:32-47
6 Lin ZB.J Pharmacol Sci,2011,115:16
7 Xu Q,Bauer R,Hendry BM,Fan TP,Zhao Z,Duez P,Simmonds MSJ,Witt CM,Lu A,Robinson N,Guo D,Hylands PJ.BMC Complem Altern Med,2013,13:132
8 Zhao S,Li S.PLoS ONE,2010,5:e11764
9 Thompson N,Lyons J.Curr Opin Pharmacol,2005,5:350-356
10 Zhang J,Zhang F,Li H,Liu C,Xia J,Ma L,Chu W,Zhang Z,Chen C,Li S,Wang S.Curr Med Chem,2012,19:2957-2975
11 Zheng XF,Sun ZX.Prog Biochem Biophys,2001,28:486-489
12 Bagal SK,Brown AD,Cox PJ,Omoto K,Owen RM,Pryde DC,Sidders B,Skerratt SE,Stevens EB,Storer RI,Swain NA.J Med Chem,2013,56:593-624
13 Bhat SP,Sharma A.Curr Drug Targets,2017,18:983-993
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15 Saxena C,Higgs RE,Zhen E,Hale JE.Expert Opin Drug Dis,2009,4:701-714
16 Kanoh N.Nat Prod Rep,2016,33:709-718
17 Liu CX,Yin QQ,Zhou HC,Wu YL,Pu JX,Xia L,Liu W,Huang X,Jiang T,Wu MX,He LC,Zhao YX,Wang XL,Xiao WL,Chen HZ,Zhao Q,Zhou AW,Wang LS,Sun HD,Chen GQ.Nat Chem Biol,2012,8:486-493
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25 Wright MH,Sieber SA.Nat Prod Rep,2016,33:681-708
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27 Wang J,Tan XF,Nguyen VS,Yang P,Zhou J,Gao M,Li Z,Lim TK,He Y,Ong CS,Lay Y,Zhang J,Zhu G,Lai SL,Ghosh D,Mok YK,Shen HM,Lin Q.Mol Cell Proteomics,2014,13:876-886
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30 Christianson R,Lokey RS.Biopolymers,2011,96:494-494
31 Ismail HM,Barton VE,Panchana M,Charoensutthivarakul S,Biagini GA,Ward SA,O'Neill PM.Angew Chem Int Ed,2016,55:6401-6405
32 Zweerink S,Pollmann T,Ninck S,Kaschani F,Kaiser M.Methods Mol Biol,2017,1491:23-46
33 Wang J,Nie Y,Li Y,Hou Y,Zhao W,Deng J,Wang PG,Bai G.J Agric Food Chem,2015,63:10013-10021
34 Zhao N,Sun M,Burns-Huang K,Jiang XJ,Ling Y,Darby C,Ehrt S,Liu G,Nathan C.PLoS ONE,2015,10:e0126211
35 Puskas LG,Dorman G,Urge L,Darvas F,Feher LZ,Hackler L.Febs J,2005,272:505
36 Hueber W,Lee BJ,Genovese MC,Bruce B,van Venrooij WJ,Smolen JS,Steinman L,Utz PJ,Robinson WH.Arthritis Rheum,2003,48:S429
37 Zhang HN,Yang L,Ling JY,Czajkowsky DM,Wang JF,Zhang XW,Zhou YM,Ge F,Yang MK,Xiong Q,Guo SJ,Le HY,Wu SF,Yan W,Liu B,Zhu H,Chen Z,Tao SC.Proc Natl Acad Sci USA,2015,112:15084-15089
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39 Jensen AJ,Martinez Molina D,Lundb?ck T.Future Med Chem,2015,7:975-978
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41 Miettinen TP,Bj?rklund M.Mol Pharm,2014,11:4395-4404
42 Lee A,Lee K,Kim D.Expert Opin Drug Dis,2016,11:707-715
43 Park K,Cho AE.J Gins Res,2017,41:534-539
44 Jin Y,Yu J,Yu YG.Chem Biol,2002,9:157-162
45 Lum PY,Armour CD,Stepaniants SB,Cavet G,Wolf MK,Butler JS,Hinshaw JC,Garnier P,Prestwich GD,Leonardson A,Garrett-Engele P,Rush CM,Bard M,Schimmack G,Phillips JW,Roberts CJ,Shoemaker DD.Cell,2004,116:121-137
46 Diestel R,Irschik H,Jansen R,KhalilaMW,Reichenbach H,Sasse F.Chembiochem,2009,10:2900-2903
47 Zeng K,Tu P.China J Chin Mater Med,2017,42:3645-3649(in Chinese)[曾克武,屠鹏飞.中国中药杂志,2017,42:3645-3649]
48 Qian Y,Han Q,Liu D,Tu P,Zeng K,Liang H.China J Chin Mater Med,2017,42:3661-3665(in Chinese)[钱薏,韩清华,刘丹,屠鹏飞,曾克武,梁鸿.中国中药杂志,2017,42:3661-3665]
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50 Wan Y,Liao L,Liu Y,Jiang Y,Liu L,Zeng K,Tu P.China J Chin Mater Med,2017,42:3650-3655(in Chinese)[万彦军,廖理曦,刘瑜琦,姜勇,刘莲英,曾克武,屠鹏飞.中国中药杂志,2017,42:3650-3655]
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54 Chen T.J Food Drug Anal,2007,15:387-399
55 Bara T,Gurzu S,Sugimura H,Bara T,Beleaua MA,Jung I.Rom J Morphol Embryo,2017,58:41-44
56 Ma S,Feng C,Zhang X,Dai G,Li C,Cheng X,Liu P,Ju W,Yu H.Complement Ther Med,2013,21:35-41