系统生物学驱动的小分子代谢组学策略创新驱动中药现代研究
|
摘要
基于系统生物学理念,聚焦小分子代谢物全局定性描述和定量表征的代谢组学策略,以其整体性表征复杂生物体系的代谢修饰与规律性调控的方法学优势,其正被宽口径应用于现代生物医学研究。尤其中药固有化学物质组成的复杂性和作用模式的系统互作属性,均与代谢组学的研究理念深度契合,因此,近年来代谢组学已经广泛应用于中药现代研究若干关键科学问题的解决。本文将以中药化学物质基础研究,中药质量控制研究,中药作用机制研究和中药配伍规律研究为主线,重点论述代谢组学策略在这些研究领域的研究实践,以期引起中医药行业对代谢组学科学价值与应用潜力的共识与重视,未来更好地实践应用代谢组学及其相关方法策略系统解决中药现代进程中的若干关键科学问题。
Systems biology driven metabolomics was designed to globally profile all the small-molecule metabolites, then snapshot the host-responses to differently biological factors by capturing the modified metabolites and associated metabolism, such as disease progression, drug treatment and genetic modifications. This method has been broadly employed to address the key questions in different niches of wide-spectrum life sciences. Basically, chemical complexity of traditional Chinese medicine indeed confers substantial challenge while we attempt to well understand therapeutic capacity. However, the philosophy of holistic diagnosis and therapeutics has been completely incorporated into the traditional Chinese medicine practice, which share the common atlas with metabolomics strategy, whereas scientists recently made considerable efforts to tailor metabolomics and associated strategy to investigate various aspects of traditional Chinese medicine involving identities of chemicals, quality control and assessment, therapeutic mechanism,compatibility priority and toxicological issue. Here, we draft this critical review by giving some typical cases to highlight the priority and limitations of metabolomics method to address those key questions for the first instance, then inspire scientific community to work together by which we have the capacity to innovate the methodology of metabolomics, and further improve the translational applications to well address the key questions associated clinical efficiency and drug discovery based on traditional Chinese medicine.
Systems biology driven metabolomics was designed to globally profile all the small-molecule metabolites, then snapshot the host-responses to differently biological factors by capturing the modified metabolites and associated metabolism, such as disease progression, drug treatment and genetic modifications. This method has been broadly employed to address the key questions in different niches of wide-spectrum life sciences. Basically, chemical complexity of traditional Chinese medicine indeed confers substantial challenge while we attempt to well understand therapeutic capacity. However, the philosophy of holistic diagnosis and therapeutics has been completely incorporated into the traditional Chinese medicine practice, which share the common atlas with metabolomics strategy, whereas scientists recently made considerable efforts to tailor metabolomics and associated strategy to investigate various aspects of traditional Chinese medicine involving identities of chemicals, quality control and assessment, therapeutic mechanism,compatibility priority and toxicological issue. Here, we draft this critical review by giving some typical cases to highlight the priority and limitations of metabolomics method to address those key questions for the first instance, then inspire scientific community to work together by which we have the capacity to innovate the methodology of metabolomics, and further improve the translational applications to well address the key questions associated clinical efficiency and drug discovery based on traditional Chinese medicine.
引文
1 Nicholson J K, Lindon J C, Holmes E.'Metabonomics':understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica, 1999, 29(11):1181-1189.
2 Allwood J W, Cheung W, Xu Y, et al. Metabolomics in melon:a new opportunity for aroma analysis. Phytochemistry, 2014, 99:61-72.
3 Bellaire A, Ischebeck T, Staedler Y, et al. Metabolism and developmentintegration of micro computed tomography data and metabolite profiling reveals metabolic reprogramming from floral initiation to silique development. New Phytol, 2014, 202(1):322-335.
4 Trushina E, Mielke M M. Recent advances in the application of metabolomics to Alzheimer's Disease. Biochimica et Biophysica Acta(BBA)-Molecular Basis of Disease, 2014, 1842(8):1232-1239.
5 Kordalewska M, Markuszewski M J. Metabolomics in cardiovascular diseases. Journal of Pharmaceutical and Biomedical Analysis, 2015,113:121-136.
6 Scrivo R, Casadei L, Valerio M, et al. Metabolomics approach in allergic and rheumatic diseases. Current Allergy and Asthma Reports, 2014, 14(6):445.
7 Tianjiao L, Shuai W, Xiansheng M, et al. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid.PLoS One, 2014, 9(1):e82499.
8 Zhang J, Mu X, Xia Y, et al. Metabolomic analysis reveals a unique urinary pattern in normozoospermic infertile men. Journal of Proteome Research, 2014, 13(6):3088-3099.
9 Ghartey J, Bastek J A, Brown A G, et al. Women with preterm birth have a distinct cervicovaginal metabolome. American Journal of Obstetrics and Gynecology, 2015, 212(6):771-776.
10 Armitage E G, Barbas C. Metabolomics in cancer biomarker discovery:current trends and future perspectives. Journal of Pharmaceutical and Biomedical Analysis, 2014, 87:1-11.
11 Mastrangelo A, Armitage E G, Garcia A, et al. Metabolomics as a tool for drug discovery and personalised medicine. A review. Curr Top Med Chem, 2014, 14(23):2627-2636.
12 Bouhifd M, Beger R, Flynn T, et al. t4Workshop report:quality assurance of metabolomics. ALTEX, 2015, 32(4):319-326.
13 Werf M J V D, Overkamp K M, Muilwijk B, et al. Microbial metabolomics:toward a platform with full metabolome coverage. Analytical Biochemistry,2007, 370(1):17-25.
14 Zenobi R. Single-cell metabolomics:analytical and biological perspectives. Science, 2013, 342(6163):1243259.
15 Lv H, Henderson J P. Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production. Journal of Proteome Research, 2011, 10(12):5547-5554.
16 Martins-De-Souza D. Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder. Dialogues in clinical neuroscience, 2014, 6(1):63.
17 陈晓亚,刘培,孟玉玲,等.植物的次生代谢.科学, 1996, 48(5):37-39.
18 黄璐琦,郭兰萍.环境胁迫下次生代谢产物的积累及道地药材的形成.中国中药杂志. 2007(4):277-280.
19 赵新峰,孔宏伟,汪江山,等. UFLC-ESI-IT-TOF鉴定六味地黄丸中的化学成分和代谢成分.世界科学技术(中医药现代化), 2009(1):153-157.
20 Wang P, Lv H T, Zhang A H, et al. Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula:liuwei dihuang Wan.2013, 36(21-22):3511-3516.缺少期刊名称
21 李睿,曾岑,王平,等.基于GC-MS和UPLC-Q-TOF-MS的麻黄汤化学成分识别.中国中药杂志, 2014, 39(4):704-709.
22 王喜军.中药药效物质基础研究的系统方法学——中医方证代谢组学.中国中药杂志, 2015(1):13-17.
23 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/QTOF-MS/MS. Journal of Pharmaceutical and Biomedical Analysis, 2008,46(3):477-490.
24 刘琦,赵宏伟,张爱华,等.基于中医方证代谢组学研究男仕胶囊治疗肾阳虚证的药效物质基础及作用机制.中国中药杂志, 2016(15):2901-2914.
25 卢盛文,孔玲,初航,等.基于中医方证代谢组学的生脉散干预老年痴呆症大鼠的药效物质基础研究.世界科学技术-中医药现代化,2016(10):1720-1729.
26 Luo X, Guo R, Xu X, et al. Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts. Mass spectrometry reviews, 2018.
27 鲁守平,隋新霞,孙群,等.药用植物次生代谢的生物学作用及生态环境因子的影响.天然产物研究与开发, 2006(6):1027-1032.
28 李玲,刘明珠,徐卫明.薄层刮板一荧光分析法在中药复方制剂.中草药, 1996(5):275-277.
29 罗集鹏.中药制剂质量控制方法的现状与展望.中药材, 1999(5):258-260.
30 谢培山.色谱指纹图谱分析是中草药质量控制的可行策略.中药新药与临床药理, 2001(3):141-151.
31 王智民,钱忠直,张启伟,等.一测多评法建立的技术指南.中国中药杂志, 2011, 36(6):657-658.
32 Shu Y, Liu Z, Zhao S, et al. Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs. Analytical and Bioanalytical Chemistry, 2017, 409(20):4849-4865.
33 Jiang Y, Vaysse J, Gilard V, et al. Quality Assessment of commercial Magnoliae Officinalis cortex by1H-NMR-based metabolomics and HPLC methods. Phytochemical Analysis, 2012, 23(4):387-395.
34 Wu J, Yang W, Pan H, et al. Geographic impact evaluation of the quality of Alismatis Rhizoma by untargeted metabolomics and quantitative assay.Journal of Separation Science, 2018, 41(4):839-846.
35 刘昌孝,陈士林,肖小河,等.中药质量标志物(Q-Marker):中药产品质量控制的新概念.中草药, 2016, 47(9):443-1457.
36 张铁军,白钢,刘昌孝.中药质量标志物的概念、核心理论与研究方法.药学学报, 2019, 54(2):187-196.
37 张铁军,许浚,韩彦琪,等.中药质量标志物(Q-marker)研究:延胡索质量评价及质量标准研究.中草药, 2016(9):1458-1467.
38 武欣,张洪兵,许浚,等.基于质量标志物的元胡止痛方配伍大鼠脑组织分布研究.中草药, 2018, 49(1):45-49.
39 Beger R D, Sun J, Schnackenberg L K. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity.Toxicology and Applied Pharmacology, 2010, 243(2):154-166.
40 杨萍,贾钰华,李杰.代谢组学技术及其在中医药领域中的应用.辽宁中医杂志, 2009, 36(1):32-35.
41 Duan L, Guo L, Wang L, et al. Application of metabolomics in toxicity evaluationoftraditionalChinesemedicines. Chinese Medicine,2018,13(1).
42 Zhang H, Zhao X, Sun Z, et al. Recognition of the toxicity of aristolochic acid. Journal of Clinical Pharmacy and Therapeutics, 2019, 44(2):157-162.
43 张莉,孟梅霞,安军民,等.基于UPLC-MS/MS~E方法研究马兜铃酸肾病大鼠的血清代谢组学.药物分析杂志, 2014, 34(11):1948-1953.
44 Michl J, Kite G C, Wanke S, et al. LC-MS-and1H NMR-based metabolomic analysis and in vitro toxicological assessment of 43Aristolochia species. Journal of Natural Products, 2016, 79(1):30-37.
45 Dong G, Wei D, Wang J, et al. Study of the cardiotoxicity of venenum bufonis in rats using an1H NMR-based metabolomics approach. PLOS ONE, 2015, 10(3):e119515.
46 梁晓萍,张政,胡坪,等.蟾酥急性毒性的代谢组学研究.高等学校化学学报, 2011, 32(1):38-43.
47 Xu W, Wang H, Chen G, et al.1H NMR-based metabonomics study on the toxicity alleviation effect of other traditional Chinese medicines in niuhuang jiedu tablet to realgar(As2S2). Journal of Ethnopharmacology,2013, 148(1):88-98.
48 马致洁,章从恩,唐进法,等.雷公藤配伍甘草降低肝毒性的代谢通路探讨.药学学报, 2017,(7):1077-1084.
49 Luo H, Gu C, Liu C, et al. Plasma metabolic profiling analysis of Strychnos nux-vomica Linn. and Tripterygium wilfordii Hook F-induced renal toxicity using metabolomics coupled with UPLC/Q-TOF-MS.Toxicology research, 2018, 7(6):1153-1163.
50 Xu T, Feng G, Zhao B, et al. A non-target urinary and serum metabolomics strategy reveals therapeutical mechanism of Radix Astragali on adjuvant-induced arthritis rats. J Chromatogr B Analyt Technol Biomed Life Sci, 2017, 1048:94-101.
51 Zhao P, Li J, Li Y, et al. Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal bufei jianpi formula for the treatment of COPD. International Journal of Chronic Obstructive Pulmonary Disease, 2014:2633.
52 Zhao P, Li J, Li Y, et al. Integrating transcriptomics, proteomics, and metabolomics profiling with system pharmacology for the delineation of long-term therapeutic mechanisms of bufei jianpi formula in treating COPD. BioMed Research International, 2017, 2017:1-17.
53 Li X, Zhang A, Sun H, et al. Metabolic characterization and pathway analysis of berberine protects against prostate cancer. Oncotarget, 2017,8(39):65022.
54 张爱华,孙晖,闫广利,等.中医方证代谢组学——中医药研究的新策略.中国中药杂志, 2015(4):569-576.
55 Sun H, Yang L, Li M, et al. UPLC-G2Si-HDMS untargeted metabolomics for identification of metabolic targets of Yin-Chen-Hao-Tang used as a therapeutic agent of dampness-heat jaundice syndrome. Journal of Chromatography B, 2018, 1081-1082:41-50.
56 孟宪生,姜民,罗国安,等.基于代谢组学的中药川芎对寒凝血瘀证大鼠作用机制研究.辽宁中医杂志, 2012, 39(2):218-221.
57 吕贝然,杨文宁,唐明敏,等.大鼠体内川芎多成分序贯代谢研究.中国中医药信息杂志, 2015, 22(4):77-82.
58 柳长凤,陈平平,刘树民,等.基于代谢组学技术的黄连解毒汤配伍规律研究.中国实验方剂学杂志, 2012, 18(13):146-152.
59 蒋怀周,鲍远程.代谢组学应用于中医药研究的思考.中医药学报,2010, 38(4):63-67.
60 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.中国天然药物, 2008,(1):43-47.
61 李先娜,邹迪,李冰冰,等.基于体内过程的关黄柏在知柏地黄丸等类方配伍环境下血中移行成分分析.世界科学技术-中医药现代化,2016, 18(10):1730-1739.
62 Cui X, Qian D, Jiang S, et al. Scutellariae Radix and Coptidis Rhizoma improve glucose and lipid metabolism in T2DM rats via regulation of the metabolic profiling and MAPK/PI3K/Akt signaling pathway. International Journal of Molecular Sciences, 2018, 19(11):3634.
63 Wu J, Zheng H, Yao X, et al. Comparative analysis of the compatibility effects of danggui-sini decoction on a blood stasis syndrome rat model using untargeted metabolomics. Journal of Chromatography B, 2019,1105:164-175.
64 Liu P, Shang E, Zhu Y, et al. Comparative analysis of compatibility effects on invigorating blood circulation for Cyperi Rhizoma series of herb pairs using untargeted metabolomics. Frontiers in Pharmacology,2017, 8:677.
65 Cui D, Wang X, Chen J, et al. Quantitative evaluation of the compatibility effects of huangqin decoction on the treatment of irinotecan-induced gastrointestinal toxicity using untargeted metabolomics. Frontiers in Pharmacology, 2017, 8:211.
2 Allwood J W, Cheung W, Xu Y, et al. Metabolomics in melon:a new opportunity for aroma analysis. Phytochemistry, 2014, 99:61-72.
3 Bellaire A, Ischebeck T, Staedler Y, et al. Metabolism and developmentintegration of micro computed tomography data and metabolite profiling reveals metabolic reprogramming from floral initiation to silique development. New Phytol, 2014, 202(1):322-335.
4 Trushina E, Mielke M M. Recent advances in the application of metabolomics to Alzheimer's Disease. Biochimica et Biophysica Acta(BBA)-Molecular Basis of Disease, 2014, 1842(8):1232-1239.
5 Kordalewska M, Markuszewski M J. Metabolomics in cardiovascular diseases. Journal of Pharmaceutical and Biomedical Analysis, 2015,113:121-136.
6 Scrivo R, Casadei L, Valerio M, et al. Metabolomics approach in allergic and rheumatic diseases. Current Allergy and Asthma Reports, 2014, 14(6):445.
7 Tianjiao L, Shuai W, Xiansheng M, et al. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid.PLoS One, 2014, 9(1):e82499.
8 Zhang J, Mu X, Xia Y, et al. Metabolomic analysis reveals a unique urinary pattern in normozoospermic infertile men. Journal of Proteome Research, 2014, 13(6):3088-3099.
9 Ghartey J, Bastek J A, Brown A G, et al. Women with preterm birth have a distinct cervicovaginal metabolome. American Journal of Obstetrics and Gynecology, 2015, 212(6):771-776.
10 Armitage E G, Barbas C. Metabolomics in cancer biomarker discovery:current trends and future perspectives. Journal of Pharmaceutical and Biomedical Analysis, 2014, 87:1-11.
11 Mastrangelo A, Armitage E G, Garcia A, et al. Metabolomics as a tool for drug discovery and personalised medicine. A review. Curr Top Med Chem, 2014, 14(23):2627-2636.
12 Bouhifd M, Beger R, Flynn T, et al. t4Workshop report:quality assurance of metabolomics. ALTEX, 2015, 32(4):319-326.
13 Werf M J V D, Overkamp K M, Muilwijk B, et al. Microbial metabolomics:toward a platform with full metabolome coverage. Analytical Biochemistry,2007, 370(1):17-25.
14 Zenobi R. Single-cell metabolomics:analytical and biological perspectives. Science, 2013, 342(6163):1243259.
15 Lv H, Henderson J P. Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production. Journal of Proteome Research, 2011, 10(12):5547-5554.
16 Martins-De-Souza D. Proteomics, metabolomics, and protein interactomics in the characterization of the molecular features of major depressive disorder. Dialogues in clinical neuroscience, 2014, 6(1):63.
17 陈晓亚,刘培,孟玉玲,等.植物的次生代谢.科学, 1996, 48(5):37-39.
18 黄璐琦,郭兰萍.环境胁迫下次生代谢产物的积累及道地药材的形成.中国中药杂志. 2007(4):277-280.
19 赵新峰,孔宏伟,汪江山,等. UFLC-ESI-IT-TOF鉴定六味地黄丸中的化学成分和代谢成分.世界科学技术(中医药现代化), 2009(1):153-157.
20 Wang P, Lv H T, Zhang A H, et al. Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula:liuwei dihuang Wan.2013, 36(21-22):3511-3516.缺少期刊名称
21 李睿,曾岑,王平,等.基于GC-MS和UPLC-Q-TOF-MS的麻黄汤化学成分识别.中国中药杂志, 2014, 39(4):704-709.
22 王喜军.中药药效物质基础研究的系统方法学——中医方证代谢组学.中国中药杂志, 2015(1):13-17.
23 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/QTOF-MS/MS. Journal of Pharmaceutical and Biomedical Analysis, 2008,46(3):477-490.
24 刘琦,赵宏伟,张爱华,等.基于中医方证代谢组学研究男仕胶囊治疗肾阳虚证的药效物质基础及作用机制.中国中药杂志, 2016(15):2901-2914.
25 卢盛文,孔玲,初航,等.基于中医方证代谢组学的生脉散干预老年痴呆症大鼠的药效物质基础研究.世界科学技术-中医药现代化,2016(10):1720-1729.
26 Luo X, Guo R, Xu X, et al. Mass spectrometry and associated technologies delineate the advantageously biomedical capacity of siderophores in different pathogenic contexts. Mass spectrometry reviews, 2018.
27 鲁守平,隋新霞,孙群,等.药用植物次生代谢的生物学作用及生态环境因子的影响.天然产物研究与开发, 2006(6):1027-1032.
28 李玲,刘明珠,徐卫明.薄层刮板一荧光分析法在中药复方制剂.中草药, 1996(5):275-277.
29 罗集鹏.中药制剂质量控制方法的现状与展望.中药材, 1999(5):258-260.
30 谢培山.色谱指纹图谱分析是中草药质量控制的可行策略.中药新药与临床药理, 2001(3):141-151.
31 王智民,钱忠直,张启伟,等.一测多评法建立的技术指南.中国中药杂志, 2011, 36(6):657-658.
32 Shu Y, Liu Z, Zhao S, et al. Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs. Analytical and Bioanalytical Chemistry, 2017, 409(20):4849-4865.
33 Jiang Y, Vaysse J, Gilard V, et al. Quality Assessment of commercial Magnoliae Officinalis cortex by1H-NMR-based metabolomics and HPLC methods. Phytochemical Analysis, 2012, 23(4):387-395.
34 Wu J, Yang W, Pan H, et al. Geographic impact evaluation of the quality of Alismatis Rhizoma by untargeted metabolomics and quantitative assay.Journal of Separation Science, 2018, 41(4):839-846.
35 刘昌孝,陈士林,肖小河,等.中药质量标志物(Q-Marker):中药产品质量控制的新概念.中草药, 2016, 47(9):443-1457.
36 张铁军,白钢,刘昌孝.中药质量标志物的概念、核心理论与研究方法.药学学报, 2019, 54(2):187-196.
37 张铁军,许浚,韩彦琪,等.中药质量标志物(Q-marker)研究:延胡索质量评价及质量标准研究.中草药, 2016(9):1458-1467.
38 武欣,张洪兵,许浚,等.基于质量标志物的元胡止痛方配伍大鼠脑组织分布研究.中草药, 2018, 49(1):45-49.
39 Beger R D, Sun J, Schnackenberg L K. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity.Toxicology and Applied Pharmacology, 2010, 243(2):154-166.
40 杨萍,贾钰华,李杰.代谢组学技术及其在中医药领域中的应用.辽宁中医杂志, 2009, 36(1):32-35.
41 Duan L, Guo L, Wang L, et al. Application of metabolomics in toxicity evaluationoftraditionalChinesemedicines. Chinese Medicine,2018,13(1).
42 Zhang H, Zhao X, Sun Z, et al. Recognition of the toxicity of aristolochic acid. Journal of Clinical Pharmacy and Therapeutics, 2019, 44(2):157-162.
43 张莉,孟梅霞,安军民,等.基于UPLC-MS/MS~E方法研究马兜铃酸肾病大鼠的血清代谢组学.药物分析杂志, 2014, 34(11):1948-1953.
44 Michl J, Kite G C, Wanke S, et al. LC-MS-and1H NMR-based metabolomic analysis and in vitro toxicological assessment of 43Aristolochia species. Journal of Natural Products, 2016, 79(1):30-37.
45 Dong G, Wei D, Wang J, et al. Study of the cardiotoxicity of venenum bufonis in rats using an1H NMR-based metabolomics approach. PLOS ONE, 2015, 10(3):e119515.
46 梁晓萍,张政,胡坪,等.蟾酥急性毒性的代谢组学研究.高等学校化学学报, 2011, 32(1):38-43.
47 Xu W, Wang H, Chen G, et al.1H NMR-based metabonomics study on the toxicity alleviation effect of other traditional Chinese medicines in niuhuang jiedu tablet to realgar(As2S2). Journal of Ethnopharmacology,2013, 148(1):88-98.
48 马致洁,章从恩,唐进法,等.雷公藤配伍甘草降低肝毒性的代谢通路探讨.药学学报, 2017,(7):1077-1084.
49 Luo H, Gu C, Liu C, et al. Plasma metabolic profiling analysis of Strychnos nux-vomica Linn. and Tripterygium wilfordii Hook F-induced renal toxicity using metabolomics coupled with UPLC/Q-TOF-MS.Toxicology research, 2018, 7(6):1153-1163.
50 Xu T, Feng G, Zhao B, et al. A non-target urinary and serum metabolomics strategy reveals therapeutical mechanism of Radix Astragali on adjuvant-induced arthritis rats. J Chromatogr B Analyt Technol Biomed Life Sci, 2017, 1048:94-101.
51 Zhao P, Li J, Li Y, et al. Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal bufei jianpi formula for the treatment of COPD. International Journal of Chronic Obstructive Pulmonary Disease, 2014:2633.
52 Zhao P, Li J, Li Y, et al. Integrating transcriptomics, proteomics, and metabolomics profiling with system pharmacology for the delineation of long-term therapeutic mechanisms of bufei jianpi formula in treating COPD. BioMed Research International, 2017, 2017:1-17.
53 Li X, Zhang A, Sun H, et al. Metabolic characterization and pathway analysis of berberine protects against prostate cancer. Oncotarget, 2017,8(39):65022.
54 张爱华,孙晖,闫广利,等.中医方证代谢组学——中医药研究的新策略.中国中药杂志, 2015(4):569-576.
55 Sun H, Yang L, Li M, et al. UPLC-G2Si-HDMS untargeted metabolomics for identification of metabolic targets of Yin-Chen-Hao-Tang used as a therapeutic agent of dampness-heat jaundice syndrome. Journal of Chromatography B, 2018, 1081-1082:41-50.
56 孟宪生,姜民,罗国安,等.基于代谢组学的中药川芎对寒凝血瘀证大鼠作用机制研究.辽宁中医杂志, 2012, 39(2):218-221.
57 吕贝然,杨文宁,唐明敏,等.大鼠体内川芎多成分序贯代谢研究.中国中医药信息杂志, 2015, 22(4):77-82.
58 柳长凤,陈平平,刘树民,等.基于代谢组学技术的黄连解毒汤配伍规律研究.中国实验方剂学杂志, 2012, 18(13):146-152.
59 蒋怀周,鲍远程.代谢组学应用于中医药研究的思考.中医药学报,2010, 38(4):63-67.
60 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.中国天然药物, 2008,(1):43-47.
61 李先娜,邹迪,李冰冰,等.基于体内过程的关黄柏在知柏地黄丸等类方配伍环境下血中移行成分分析.世界科学技术-中医药现代化,2016, 18(10):1730-1739.
62 Cui X, Qian D, Jiang S, et al. Scutellariae Radix and Coptidis Rhizoma improve glucose and lipid metabolism in T2DM rats via regulation of the metabolic profiling and MAPK/PI3K/Akt signaling pathway. International Journal of Molecular Sciences, 2018, 19(11):3634.
63 Wu J, Zheng H, Yao X, et al. Comparative analysis of the compatibility effects of danggui-sini decoction on a blood stasis syndrome rat model using untargeted metabolomics. Journal of Chromatography B, 2019,1105:164-175.
64 Liu P, Shang E, Zhu Y, et al. Comparative analysis of compatibility effects on invigorating blood circulation for Cyperi Rhizoma series of herb pairs using untargeted metabolomics. Frontiers in Pharmacology,2017, 8:677.
65 Cui D, Wang X, Chen J, et al. Quantitative evaluation of the compatibility effects of huangqin decoction on the treatment of irinotecan-induced gastrointestinal toxicity using untargeted metabolomics. Frontiers in Pharmacology, 2017, 8:211.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |