中药药效物质基础研究的系统方法学——中医方证代谢组学Methodology for systematic analysis of in vivo efficacy material base of traditional Chinese medicine——Chinmedomics
王喜军;
WANG Xi-jun;Heilongjiang University of Chinese Medicine;
摘要(Abstract):
中药药效物质基础是指中药中含有的能够表达药物临床疗效的化学成分总称。而中医临床使用的是方剂,中药饮片是原料,方剂才是药物。同一中药在不同配伍环境下在体内表达不同的体内直接作用物质,从而实现药效的配伍取向。所以中药药效物质基础研究应该从方剂入手,而评价方剂的临床药效是发现药效物质基础的前提。在临床上,方剂对应的是证候或病,中医证候/病的客观正确诊断,阐释证候/病的生物学本质,发现证候/病的生物标记物,建立临床疗效的生物评价体系是评价方剂临床疗效进而发现中药药效物质基础的基本前提。基于中药复方给药形式的特殊性及方证对应疗效的专属性,笔者的团队以证候为起点,从方剂入手,建立了系统的关联"证候诊断-方剂效应评价-体内直接作用物质分析"的方法学——中医方证代谢组学(Chinmedomics),将中药血清药物化学和代谢组学有机结合,在解决证候生物标记物的基础上,建立方剂药效生物评价体系,发现并确定中药药效物质基础,进而解决与药效物质基础相关的中药有效性及安全性等质量问题,以及基于临床有效性的中药创新药物发现问题。
The efficacy material base of traditional Chinese medicines( TCMs) is those constituents absorbed in blood and show the efficacy of TCMs after oral administration of a TCM formula. In TCM,formula consisted of more than one herbal drug is the clinical medication form which corresponding to TCM syndrome. The efficacy material base of TCMs had to be found in the condition of compatibility and efficacy of TCM formula. Therefore we take the biological characters of TCM syndrome as a research starting point,taking formula as object,through the integration of serum pharmacochemistry of TCM methods and metabolomics technologies,establish a system research methodology of the efficacy material basis in vivo--Chinmedomics. The use of metabolomics technology is used to fully understand nature biology on syndromes or disease,identify biomarkers for disease to bridging disease animal model,establishing the biological evaluation system of traditional Chinese medicine. On the basis of the validity of the premise,the use of serum pharmacochemistry of TCM to analysis in vivo directly substance after oral prescription and dynamic law,combined with changes law of the endogenous disease biomarkers( pharmacodynamic markers of TCM),Though establishing two variable correlation analysis method between Chinese chemical compositions in serum exogenous and endogenous biomarkers,to extract TCM compositions highly correlated with the endogenous marker as potential basis for traditional Chinese medicines,and to biological validation to determine the efficacy material basis of TCM.
关键词(KeyWords):
中医方证代谢组学;中药血清药物化学;代谢组学;体内药效物质基础;方法学
Chinmedomics;serum pharmacochemistry of TCM;metabonomics;efficacy material base;methodology
基金项目(Foundation): 国家自然科学基金重点项目(81470093)
作者(Author):
王喜军;
WANG Xi-jun;Heilongjiang University of Chinese Medicine;
Email:
DOI:
参考文献(References):
- [1]Nickavar B,Abolhasani L.Bioactivity-guided separation of anα-amylase inhibitor flavonoid from Salvia virgata[J].Iran J Pharm Res,2013,12(1):57.
- [2]De Sousa LR,Ramalho S D,Burger M C,et al.Isolation of arginase inhibitors from the bioactivity-guided fractionation of Byrsonima coccolobifolia leaves and stems[J].J Nat Prod,2014,77(2):392.
- [3]Lou Y,Zhang H,He H,et al.Isolation and identification of phaseⅠmetabolites of curcumol in rats[J].Drug Metab Dispos,2010,38(11):2014.
- [4]Xu H,Li Y,Che X,et al.Metabolism of salvianolic acid A and antioxidant activities of its methylated metabolites[J].Drug Metab Dispos,2014,42(2):274.
- [5]Kong W J,Wang J B,Zang Q C,et al.A novel"target constituent knock-out"strategy coupled with TLC,UPLC-ELSD and microcalorimetry for preliminary screening of antibacterial constituents in calculus bovis[J].J Chromatogr B Analyt Technol Biomed Life Sci,2011,879(30):3565.
- [6]王喜军.中药及中药复方的血清药物化学研究[J].世界科学技术——中药现代化,2002,4(2):1.
- [7]王喜军.中药血清药物化学学科的形成及发展[J].世界科学技术——中医药现代化,2010,12(4):33.
- [8]Wang H,Sun H,Zhang A,et al.Rapid identification and comparative analysis of the chemical constituents and metabolites of Phellodendri amurensis cortex and Zhibai dihuang pill by ultraperformance liquid chromatography with quadrupole TOF-MS[J].J Sep Sci,2013,36(24):3874.
- [9]Wang X,Sun W,Sun H,et al.Analysis of the constituents in the rat plasma after oral administration of Yin Chen Hao Tang by UPLC/Q-TOF-MS/MS[J].J Pharm Biomed Anal,2008,46(3):477.
- [10]王喜军,孙文军,孙晖,等.茵陈蒿汤不同配伍变化对大鼠血中移行成分的影响[J].中国天然药物,2008,6(1):43.
- [11]王喜军.基于临床有效性的中药药效物质基础生物分析体系[J].世界科学技术——中医药现代化,2013,15(1):16.
- [12]张积强,陈强,刘宗怀.抗疟新药青蒿素的研究[J].陕西化工,1996,4:81.
- [13]唐希灿.石杉碱甲(双益平):一种有望治疗早老性痴呆症的药物[J].中国药理学报,1996,17(6):81.
- [14]北京制药工业研究所.川芎Ⅰ号碱(川芎嗪)技术鉴定会报道[J].医药工业,1977,Z1:55.
- [15]Li S,Chou G,Hseu Y,et al.Isolation of anticancer constituents from flos genkwa(Daphne genkwa Sieb.et Zucc.)through bioassay-guided procedures[J].Chem Cent J,2013,7(1):159.
- [16]Meng Q X,Roubin R H,Hanrahan J R.Ethnopharmacological and bioactivity guided investigation of five TCM anticancer herbs[J].J Ethnopharmacol,2013,148(1):229.
- [17]黄熙,陈可冀.证治药动学新假说的理论和实践[J].中医杂志,1997,38(12):745.
- [18]黄熙.方剂体内/血清成分谱与靶成分概念的提出及意义[J].第四军医大学学报,1999,20(4):277.
- [19]黄熙,范荣,张海男,等.生物方剂分析药理:阐明方剂吸收生物活性成分的研究策略[J].中草药,2010,41(3):337.
- [20]邱峰,姚新生.中药体内直接物质基础研究的新思路[J].中药药理与临床,1999,15(3):1.
- [21]邱峰.浅谈中药成分体内代谢研究[J].国际药学研究杂志,2010,37(5):321.
- [22]杨秀伟.基于体内过程的中药有效成分和有效效应物质的发现策略[J].中国中药杂志,2007,32(5):365.
- [23]杨秀伟,张鹏,寇桂风,等.基于体内过程的中药药效物质基础研究[J].北京:第九届中国中西医结合实验医学学术研讨会,2009:302.
- [24]许海玉,唐仕欢,陈建新,等.基于代谢组学的中药“组效关系”研究思路与策略[J].世界科学技术——中医药现代化,2011,13(1):30.
- [25]齐炼文,周建良,郝海平,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.
- [26]Gong P,Cui N,Wu L,et al.Chemicalome and metabolome matching approach to elucidating biological metabolic networks of complex mixtures[J].Anal Chem,2012,84(6):2995.
- [27]Yang M,Cheng C,Yang J,et al.Metabolite profiling and characterization for medicinal herbal remedies[J].Curr Drug Metab,2012,13(5):535.
- [28]Liu Z,Liu M,Qi Y,et al.Plasma pharmacochemistry combined with microdialysis to screen potential bioactive components and their metabolites in Anemarrhena asphodeloides saponin extractusing ultrahigh-performance liquid chromatography/quadrupoletime-of-flight mass spectrometry[J].J Sep Sci,2013,36(9/10):1659.
- [29]Hu Y,Jiang P,Wang S,et al.Plasma pharmacochemistry based approach to screening potential bioactive components in HuangLian-Jie-Du-Tang using high performance liquid chromatography coupled with mass spectrometric detection[J].J Ethnopharmacol,2012,141(2):728.
- [30]Zeng W,Han H,Tao Y,et al.Identification of bio-active metabolites of gentiopicroside by UPLC/Q-TOF MS and NMR[J].Biomed Chromatogr,2013,27(9):1129.
- [31]潘学强,吴燕川,龚慕辛,等.外翻肠囊吸收成分与药效相关研究吴茱萸汤治疗偏头痛的药效物质[J].中国中药杂志,2014,39(1):126.
- [32]Wang X,Sun W,Sun H,et al.Analysis of the constituents in the rat plasma after oral administration of Yin Chen Hao Tang by UPLC/Q-TOF-MS/MS[J].J Pharm Biomed Anal,2008,46(3):477.
- [33]Wang X,Sun H,Zhang A,et al.Pharmacokinetics screening for multi-components absorbed in the rat plasma after oral administration traditional Chinese medicine formula Yin-Chen-Hao-Tang by ultra performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight mass spectrometry combined with pattern recognition methods[J].Analyst,2011,136(23):5068.
- [34]Lv H,Sun H,Sun W,et al.Pharmacokinetic studies of a Chinese triple herbal drug formula[J].Phytomedicine,2008,15(11):993.
- [35]王喜军,孙文军,张宁,等.六味地黄丸血中移行成分的分离及结构鉴定[J].中国天然药物,2007,5(4):277.
- [36]王喜军,张宁,孙晖,等.六味地黄丸的血清药物化学研究[J].中国天然药物,2004,2(4):219.
- [37]吴芳芳,王喜军,韩莹,等.基于UPLC-HDMS技术的生脉散血清药物化学初步研究[J].世界科学技术——中医药现代化,2010,12(4):657.
- [38]王喜军,陈曦,杨舸,等.枳术丸口服给药后血中移行成分分析及其定量研究[J].世界科学技术——中医药现代化,2007,9(2):54.
- [39]Cao H,Chen X,Sun H,et al.Pharmacokinetics-based elucidation on disparity in clinical effectiveness between varieties of Zhi Zhu Wan,a traditional Chinese medical formula[J].J Ethnopharmacol,2010,128(3):606.
- [40]杨波,张爱华,董巍,等.酸枣仁汤的血清药物化学及不同配伍变化对血中移行成分的影响研究[J].中医药信息,2013,30(4):44.
- [41]Yan G L,Zhang A H,Sun H,et al.An effective method for determining the ingredients of Shuanghuanglian formula in blood samples using high-resolution LC-MS coupled with background subtraction and a multiple data processing approach[J].J Sep Sci,2013,36(19):3191.
- [42]Wang Ping,Yin Quanwei,Zhang Aihua,et al.Preliminary iden-tification of the absorbed bioactive components and metabolites in rat plasma after oral administration of Shaoyao-Gancao decoction by ultra-performance liquid chromatography with electrospray ionization tandem mass spectrometry[J].Pharmacogn Mag,2014,10(40):497.
- [43]曹洪欣,王喜军,于友华,等.中药复方安替威血清药物化学和抗SARS病毒试验研究[J].中国中药杂志,2004,29(3):281.
- [44]王喜军.中药血清药物化学[M].北京:科技出版社,2010.
- [45]王喜军.基于临床有效性的中药药效物质基础生物分析体系[J].世界科学技术——中医药现代化,2013,15(1):16.
- [46]Wang X,Zhang A,Sun H.Future perspectives of Chinese medical formulae:chinmedomics as an effector[J].OMICS,2012,16(7/8):414.
- [47]Wang X,Zhang A,Han Y,et al.Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease[J].Mol Cell Proteomics,2012,11(8):370.
- [48]Wang X,Zhang A,Sun H.Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma[J].Hepatology,2013,57(5):2072.
- [49]Wang X,Yang B,Sun H,et al.Pattern recognition approaches and computational systems tools for ultra performance liquid chromatography-mass spectrometry-based comprehensive metabolomicprofiling and pathways analysis of biological data sets[J].Anal Chem,2012,84(1):428.
- [50]Wang X,Wang H,Zhang A,et al.Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis[J].J Proteome Res,2012,11(2):1284.
- [51]Wang X,Yang B,Zhang A,et al.Potential drug targets on insomnia and intervention effects of Jujuboside A through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition approach[J].J Proteomics,2012,75(4):1411.
- [52]Zhang A,Sun H,Han Y,et al.Urinary metabolic biomarker and pathway study of hepatitis B virus infected patients based on UPLC-MS system[J].PLoS One,2013,8(5):e64381.
- [53]Zhang A,Sun H,Han Y,et al.Exploratory urinary metabolic biomarkers and pathways using UPLC-Q-TOF-HDMS coupled with pattern recognition approach[J].Analyst,2012,137(18):4200.
- [54]张爱华,孙晖,闫广利,等.“血清药物化学-药代(效)动力学-系统生物学”三维整合体系研究中药复方的构建及其在茵陈蒿汤分析中的应用[J].中国中药杂志,2013,38(21):3786.