基于“整体观”探讨中药的研究思维和方法
|
摘要
中药源于自然,治疗疾病有自身的优势和特点,其作用方式一直是中药研究者们不断研究和探索的重要内容。本文从中医的"整体观"对中药起效机制进行深入思考,认为中药成分多样可契合生物多靶,而生物靶标之间的协同作用是中药起效机制的重要补充;此外,中药对情志及肠道菌群稳态的调节作用也不容忽视,或许可为今后开展中药作用机制的研究提供新的思维和方法。
Chinese medicine originates from nature, and the mechanism of it for treating diseases must be different from chemical drugs. It has always been an important part of the research and exploration for Chinese medicine researchers.This paper takes a deep consideration on the mechanism of Chinese medicine from the "holistic view" of Chinese medicine, and explores other possible more important modes of Chinese medicine works, so as to provide new thinking and method for the future research on the mechanism of action of Chinese medicine.
Chinese medicine originates from nature, and the mechanism of it for treating diseases must be different from chemical drugs. It has always been an important part of the research and exploration for Chinese medicine researchers.This paper takes a deep consideration on the mechanism of Chinese medicine from the "holistic view" of Chinese medicine, and explores other possible more important modes of Chinese medicine works, so as to provide new thinking and method for the future research on the mechanism of action of Chinese medicine.
引文
1蒋宁,齐春会,曹亮,等.新形势·新策略--中药新药及健康产品研发与国际化发展.中国药理学与毒理学杂志,2018,32(1).
2陆茵,张大方.中药药理学(第1版).北京:人民卫生出版社,2012.
3姜廷良.桂枝汤现代研究与应用.北京:人民卫生出版社,2011.
4 Xu X,Zhu Y.Curcumin inhibits human non-small cell lung cancer xenografts by targeting STAT3 pathway.Am J Transl Res,2017,9(8):3633.
5 Kalashnikova I,Mazar J,Neal C J,et al.Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma.Nanoscale,2017,9(29):10375-10387.
6 Dong H S,Nam J H,Lee E S,et al.Inhibition of Ca 2+releaseactivated Ca 2+channel(CRAC)by curcumin and caffeic acid phenethyl ester(CAPE)via electrophilic addition to a cysteine residue of Orai1.Biochem Bioph Res Co,2012,428(1):56-61.
7 Cragg G M,Newman D J.A tale of two tumor targets:topoisomerase Iand tubulin.The Wall and Wani contribution to cancer chemotherapy.JNat Prod(Gorakhpur),2004,67(2):232-244.
8 Wang J,Zhang C J,Wan N C,et al.Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum.Nat Commun,2015,6:10111.
9郭宗儒.药物的杂泛性.药学学报,2011(4):361-369.
10 Schreiber G,Keating A E.Protein binding specificity versus promiscuity.Curr Opin Struct Biol,2011,21(1):50-61.
11 Chen W,Miao Y Q,Fan D J,et al.Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.AAPS PharmSciTech,2011,12(2):705-711.
12 Bo W,Blennow G.A Study on the Fate of Curcumin in the Rat.Basic Clin Pharmacol Toxicol,2010,43(2):86-92.
13张海防,郭健新,黄罗生,等.羟基红花黄色素A在大鼠体内的药代动力学.中国药科大学学报,2006,37(5):456-460.
14王逢春,王敏,李秀敏,等.LC-MS/MS测定大鼠血浆中没食子酸丙酯浓度.医学研究生学报,2013,26(10):1049-1052.
15韦忠红,余苏云,陈文星,等.微量中药成分的起效机制研究不容忽视--“遗传协同致死”模式有助于发现并阐释中药显效物质基础及起效机制.世界科学技术-中医药现代化,2017,19(9):1424-1429.
16 Stermitz F R,Lorenz P,Tawara J N,et al.Synergy in a medicinal plant:Antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin,a multidrug pump inhibitor.Proc Natl Acad Sci U S A,2000,97(4):1433-1437.
17余苏云,陆茵.中药起效作用机制探讨.中国药理学与毒理学杂志,2018,32(5):347-354.
18 Bryant H E,Schultz N,Thomas H D,et al.Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose)polymerase.Nature,2007,434(7035):913-917.
19 Farmer H,McCabe N,Lord C J,et al.Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature,2005,434(7035):917-921.
20 Nijman S M,Friend S H.Cancer.Potential of the synthetic lethality principle.Science(New York,N.Y.),2013,342(6160):809-811.
21 Mullard A.Synthetic lethality screens point the way to new cancer drug targets.Nature Reviews Drug Discovery,2017,16(10):736.
22 Wang T,Yu H,Hughes N W,et al.Gene essentiality profiling reveals gene networks and synthetic lethal interactions with oncogenic ras.Cell,2017,168(5):890-903,e15.
23 Cox A D,Fesik S W,Kimmelman A C,et al.Drugging the undruggable RAS:mission possible.Nature Reviews Drug Discovery,2014,13(11):828.
24 Wilck N,Matus M G,Kearney S M,et al.Salt-responsive gut commensal modulates TH17 axis and disease.Nature,2017,551(7682)
25 Wu H,Esteve E,Tremaroli V,et al.Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes,contributing to the therapeutic effects of the drug.Nat Med,2017,23(7):850.
26 Guglielmi G.How gut microbes are joining the fight against cancer.Nature,2018,557(7706):482-484.
27 Perry R J,Peng L,Barry N A,et al.Acetate mediates a microbiomebrain-β-cell axis to promote metabolic syndrome.Nature,2016,534(7606):213-217.
28 Sergio S V,David R,Mónica M M,et al.Gut bacteria metabolism impacts immune recovery in HIV-infected individuals.EBioMedicine,2016,8(C):203-216.
29 Yip L Y,Aw C C,Lee S H,et al.The liver–gut microbiota axis modulates hepatotoxicity of tacrine in the rat.Hepatology,2017,67(1):282.
30 Sampson T,Debelius J,Thron T,et al.Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease.Cell,2016,167(6):1469.
31 Bailey C J.Metformin:historical overview.Diabetologia,2017,60(9):1-11.
32 Bailey C J,Wilcock C,Scarpello J H B.Metformin and the intestine.Diabetologia,2008,51(8):1552-1553.
33 Bauer P V,Duca F A,Waise T,et al.Metformin alters upper small intestinal microbiota that impact a Glucose-SGLT1-Sensing glucoregulatory pathway.Cell Metab,2018,27(1):101-117.
34 Zhang X,Zhao Y,Zhang M,et al.Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.PLoS One,2012,7(8):e42529.
35 Zhang Z,Chen Y,Xiang L,et al.Effect of curcumin on the diversity of gut microbiota in ovariectomized rats.Nutrients,2017,9(10):1146.
36 Mu J,Zhuang X,Wang Q,et al.Interspecies communication between plant and mouse gut host cells through edible plant derived exosomelike nanoparticles.Mol Nutr Food Res,2014,58(7):1561-1573.
37 Yoo B B,Mazmanian S K.The enteric network:interactions between the immune and nervous systems of the gut.Immunity,2017,46(6):910-926.
38 Han W,Tellez L A,Perkins M H,et al.A neural circuit for gut-induced reward.Cell,2018,175(3):887-888.
39 Foster J A,McVey N K A.Gut-brain axis:how the microbiome influences anxiety and depression.Trends Neurosci,2013,36(5):305-312.
40 Vuong H E,Yano J M,Fung T C,et al.The microbiome and host behavior.Annu Rev Neurosci,2017,40:21-49.
41 van der Lely AJ,Tsch?p M,Heiman M L,et al.Biological,physiological,pathophysiological,and pharmacological aspects of ghrelin.Endocr Rev,2004,25(3):426-457.
42 Sanger G J,Lee K.Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders.Nat Rev Drug Discov,2008,7(3):241-254.
43梁瑞峰,葛文静,王慧森,等.痛泻要方加减引经药防风对肠易激综合征大鼠内脏敏感性及脑肠轴不同靶点脑肠肽的影响.中国实验方剂学杂志,2018,24(2):152-157.
44陆敏,张伟,姚青,等.肠康方对肠易激综合征内脏高敏感模型大鼠脑肠轴5-羟色胺转运体的作用.世界华人消化杂志,2015,(8):1231-1237.
2陆茵,张大方.中药药理学(第1版).北京:人民卫生出版社,2012.
3姜廷良.桂枝汤现代研究与应用.北京:人民卫生出版社,2011.
4 Xu X,Zhu Y.Curcumin inhibits human non-small cell lung cancer xenografts by targeting STAT3 pathway.Am J Transl Res,2017,9(8):3633.
5 Kalashnikova I,Mazar J,Neal C J,et al.Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma.Nanoscale,2017,9(29):10375-10387.
6 Dong H S,Nam J H,Lee E S,et al.Inhibition of Ca 2+releaseactivated Ca 2+channel(CRAC)by curcumin and caffeic acid phenethyl ester(CAPE)via electrophilic addition to a cysteine residue of Orai1.Biochem Bioph Res Co,2012,428(1):56-61.
7 Cragg G M,Newman D J.A tale of two tumor targets:topoisomerase Iand tubulin.The Wall and Wani contribution to cancer chemotherapy.JNat Prod(Gorakhpur),2004,67(2):232-244.
8 Wang J,Zhang C J,Wan N C,et al.Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum.Nat Commun,2015,6:10111.
9郭宗儒.药物的杂泛性.药学学报,2011(4):361-369.
10 Schreiber G,Keating A E.Protein binding specificity versus promiscuity.Curr Opin Struct Biol,2011,21(1):50-61.
11 Chen W,Miao Y Q,Fan D J,et al.Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.AAPS PharmSciTech,2011,12(2):705-711.
12 Bo W,Blennow G.A Study on the Fate of Curcumin in the Rat.Basic Clin Pharmacol Toxicol,2010,43(2):86-92.
13张海防,郭健新,黄罗生,等.羟基红花黄色素A在大鼠体内的药代动力学.中国药科大学学报,2006,37(5):456-460.
14王逢春,王敏,李秀敏,等.LC-MS/MS测定大鼠血浆中没食子酸丙酯浓度.医学研究生学报,2013,26(10):1049-1052.
15韦忠红,余苏云,陈文星,等.微量中药成分的起效机制研究不容忽视--“遗传协同致死”模式有助于发现并阐释中药显效物质基础及起效机制.世界科学技术-中医药现代化,2017,19(9):1424-1429.
16 Stermitz F R,Lorenz P,Tawara J N,et al.Synergy in a medicinal plant:Antimicrobial action of berberine potentiated by 5'-methoxyhydnocarpin,a multidrug pump inhibitor.Proc Natl Acad Sci U S A,2000,97(4):1433-1437.
17余苏云,陆茵.中药起效作用机制探讨.中国药理学与毒理学杂志,2018,32(5):347-354.
18 Bryant H E,Schultz N,Thomas H D,et al.Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose)polymerase.Nature,2007,434(7035):913-917.
19 Farmer H,McCabe N,Lord C J,et al.Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.Nature,2005,434(7035):917-921.
20 Nijman S M,Friend S H.Cancer.Potential of the synthetic lethality principle.Science(New York,N.Y.),2013,342(6160):809-811.
21 Mullard A.Synthetic lethality screens point the way to new cancer drug targets.Nature Reviews Drug Discovery,2017,16(10):736.
22 Wang T,Yu H,Hughes N W,et al.Gene essentiality profiling reveals gene networks and synthetic lethal interactions with oncogenic ras.Cell,2017,168(5):890-903,e15.
23 Cox A D,Fesik S W,Kimmelman A C,et al.Drugging the undruggable RAS:mission possible.Nature Reviews Drug Discovery,2014,13(11):828.
24 Wilck N,Matus M G,Kearney S M,et al.Salt-responsive gut commensal modulates TH17 axis and disease.Nature,2017,551(7682)
25 Wu H,Esteve E,Tremaroli V,et al.Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes,contributing to the therapeutic effects of the drug.Nat Med,2017,23(7):850.
26 Guglielmi G.How gut microbes are joining the fight against cancer.Nature,2018,557(7706):482-484.
27 Perry R J,Peng L,Barry N A,et al.Acetate mediates a microbiomebrain-β-cell axis to promote metabolic syndrome.Nature,2016,534(7606):213-217.
28 Sergio S V,David R,Mónica M M,et al.Gut bacteria metabolism impacts immune recovery in HIV-infected individuals.EBioMedicine,2016,8(C):203-216.
29 Yip L Y,Aw C C,Lee S H,et al.The liver–gut microbiota axis modulates hepatotoxicity of tacrine in the rat.Hepatology,2017,67(1):282.
30 Sampson T,Debelius J,Thron T,et al.Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease.Cell,2016,167(6):1469.
31 Bailey C J.Metformin:historical overview.Diabetologia,2017,60(9):1-11.
32 Bailey C J,Wilcock C,Scarpello J H B.Metformin and the intestine.Diabetologia,2008,51(8):1552-1553.
33 Bauer P V,Duca F A,Waise T,et al.Metformin alters upper small intestinal microbiota that impact a Glucose-SGLT1-Sensing glucoregulatory pathway.Cell Metab,2018,27(1):101-117.
34 Zhang X,Zhao Y,Zhang M,et al.Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.PLoS One,2012,7(8):e42529.
35 Zhang Z,Chen Y,Xiang L,et al.Effect of curcumin on the diversity of gut microbiota in ovariectomized rats.Nutrients,2017,9(10):1146.
36 Mu J,Zhuang X,Wang Q,et al.Interspecies communication between plant and mouse gut host cells through edible plant derived exosomelike nanoparticles.Mol Nutr Food Res,2014,58(7):1561-1573.
37 Yoo B B,Mazmanian S K.The enteric network:interactions between the immune and nervous systems of the gut.Immunity,2017,46(6):910-926.
38 Han W,Tellez L A,Perkins M H,et al.A neural circuit for gut-induced reward.Cell,2018,175(3):887-888.
39 Foster J A,McVey N K A.Gut-brain axis:how the microbiome influences anxiety and depression.Trends Neurosci,2013,36(5):305-312.
40 Vuong H E,Yano J M,Fung T C,et al.The microbiome and host behavior.Annu Rev Neurosci,2017,40:21-49.
41 van der Lely AJ,Tsch?p M,Heiman M L,et al.Biological,physiological,pathophysiological,and pharmacological aspects of ghrelin.Endocr Rev,2004,25(3):426-457.
42 Sanger G J,Lee K.Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders.Nat Rev Drug Discov,2008,7(3):241-254.
43梁瑞峰,葛文静,王慧森,等.痛泻要方加减引经药防风对肠易激综合征大鼠内脏敏感性及脑肠轴不同靶点脑肠肽的影响.中国实验方剂学杂志,2018,24(2):152-157.
44陆敏,张伟,姚青,等.肠康方对肠易激综合征内脏高敏感模型大鼠脑肠轴5-羟色胺转运体的作用.世界华人消化杂志,2015,(8):1231-1237.