目的 以葛根传统的降糖功效(中医称“止消渴”)作为研究对象,揭示葛根主要活性成分的作用靶点,探讨其多成分-多靶点-多通路的作用机制。方法 针对葛根中27个活性成分,采用反向药效团匹配方法进行作用靶点预测和作用机制探讨。通过对PharmMapper数据库和 DrugBank 数据库中降糖药物靶点的比对筛选,借助String数据库挖掘靶点信息关系,并采用 Cytoscape 软件构建成分-靶点-通路网络。结果 葛根降糖的潜在活性成分主要有18个,涉及9个靶点和25条代谢通路,其中潜在活性成分主要包括葛根素、3'-羟基葛根素、3'-甲氧基葛根素和大豆素等;潜在作用靶点主要有胰岛素受体、血管紧张素转换酶2、过氧化物酶体增殖活化受体γ等;代谢通路主要有低氧诱导因子-1(hypoxia-inducible factor-1, HIF-1)信号通路、肾素-血管紧张素系统、FoxO信号通路和腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)信号通路等。结论 本实验运用网络药理学方法和技术,从分子网络层面揭示了葛根主要活性成分降糖作用的多靶点预测、多通路的作用模式,为葛根降糖作用机制的深入探讨提供了理论依据和线索。
Abstract
OBJECTIVE To predict the action targets of the hypoglycemic bioactive components of Gegen (Puerariae Lobatae Radix), and investigate the “multi-components, multi-targets and multi-pathways” mechanism. METHODS Based on the network pharmacology, the reported 27 active ingredients in Gegen were used to predict the action target and reveal the action mechanism via reversed pharmacophore matching method, database mining, and some other methods. The PharmMapper database and DrugBank database were applied to screen the hypoglycemic drug targets approved by FDA. Additionlly, the information of these targets and their intentions were revealed by the String database. At last the ingredients-targets-pathways network was constructed via the Cytoscape software. RESULTS Studies found that Gegen contained hypoglycemic components, such as:puerarin, 3'-hydroxypuerarin, 3'-methoxypuerarin, daidzein and so on. Their actions involved in 9 potential targets and 25 energy metabolism or signal transmutation relevant biological processes, e.g. insulin receptor, angiotensin-converting enzyme 2 (ACE2), and peroxisome proliferator-activated receptor γ (PPARγ). While the mainly metabolism and signal transmutation pathways were HIF-1 signaling pathway, renin-angiotensin system, FoxO signaling pathway, AMPK signaling pathway and so on. CONCLUSION From the view of molecular network, this study applied provides network pharmacology methods and technologies to clarify the multi-components, multi-targets and multi-pathways of Gegen on the hypoglycemic effect, and it provides a theoretical basis and a clue for further exploration of the hypoglycemic mechanism of Gegen.
关键词
网络药理学 /
葛根 /
糖尿病 /
靶点 /
反向药效团匹配
{{custom_keyword}} /
Key words
network pharmacology /
Puerariae Lobatae Radix /
diabetes /
target /
PharmMapper
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] TAO L J, CHEN W T, JING L, et al. A network pharmacology approach to establish the pharmacological mechanism of jiaweixianjitang on inflammatory bowel disease. Biomed Rep, 2017, 6(3):272-278.
[2] ZHAO Z Y,SHEN X, HU B Y, et al. Systems pharmacology based researching of radix bupleuri in treatment of different emotional diseases. Chin Pharm J (中国药学杂志), 2016, 51(13):1131-1136.
[3] YUAN W F, TU M Y, CHEN C, et al. Network pharmacology study of compound danshen dropping pill based on molecular docking and recognition of biological network function modules. Chin Pharm J (中国药学杂志), 2017, 52(9):743-749.
[4] ZHU W T, FAN X M, WEI H, et al. Mechanism research of apatinib-treated breast cancer based on network pharmacology. Chin Pharm J (中国药学杂志), 2016, 51(18):1569-1573.
[5] GAO Y, GAO L, GAO X X, et al. An exploration in the action targets for antidepressant bioactive components of xiaoyaosan based on network pharmacology. Acta Pharm Sin (药学学报), 2015, 50(12):1589-1595.
[6] JINLONG R, PENG L, JINAN W, et al. TCMSP:a database of systems pharmacology for drug discovery from herbalmedicines. J Cheminformatics, 2014, 6(1):1-14.
[7] WONNG K H, RAZMOVSKI-NAUMOVSKI V, LI K M, et al. Comparing morphological, chemical and anti-diabetic characteristics of Puerariae Lobatae Radix and puerariae thomsonii radix. J Ethnopharmacol, 2015, 164:53-63.
[8] ZAN L X. Kudzu root's pharmacology and comprehensive development. Asia-Pac Tradit Med (亚太传统医药), 2010, 6(12):161-164.
[9] LIU J, ZHANG H, JI B, et al. A diet formula of Puerariae Radix, Lycium barbarum, Crataegus pinnatifida, and Polygonati rhizoma alleviates insulin resistance and hepatic steatosis in CD-1 mice and HepG2 cells. Food Funct, 2014, 5(5):1038-1049.
[10] CAI C C, XU Y Y, WANG H X, et al. The study of therapeutic effect and mechanism of Puerariae Radix polysaccharides on type 2 diabetes mellitus rats. Tianjin J Tradit Chin Med (天津中医药), 2014, 31(2):94-97.
[11] ZHAO Q Q, LI X, ZENG M L, et al. A network pharmacology based study of regulation effects of the main active components in honghua injection on cerebrovascular disease network. Chin Pharm J (中国药学杂志), 2015, 50(16):1402-1407.
[12] ULBRICHT C, COSTA D, DAM C, et al. An evidence-based systematic review of kudzu(Pueraria lobata) by the natural standard research collaboration. J Diet Suppl, 2014, 12(1):36-104.
[13] LI P, PAN G P, JIA M, et al. Effect of xin mai jia on atherosclerosis in rats. Genet Mol Res, 2015, 2(14):6018-6027.
[14] WANG Z M, XUE J T, JING Y, et al. Study on quality standard of Xinmaijai i capsule. J Xinxiang Med Coll (新乡医学院学报), 2017, 34(2):107-109.
[15] LIU H, LI Z L, GUO J, et al. Chemical constituents of the root of Pueraria lobata. J Shenyang Pharm Univ (沈阳药科大学学报), 2009, 26(11):882-885.
[16] ZHANG D H, DONG Q B, PENG S G. Study on the chemical constituents, pharmacological actions and clinical application of Radix Puerariae. Capit Med (首都医药), 2007, 6(12):44-45.
[17] LI G H, ZHANG Q W, WANG Y T. Chemical constituents from roots of Pueraria lobata. China J Chin Mater Med (中国中药杂志), 2010, 35(23):3156-3160.
[18] DU D H, LIU Y M. Research advances on treatment for type 2 diabetes and complications by effective component of Radix Pueraria. Chin Arch Tradit Chin Med (中华中医药学刊), 2008, 26(10):2157-2160.
[19] XIE M, CHEN F, CHEN Z. Research progress of HIF-1α and diabetes mellitus. Mod Prev Med (现代预防医学), 2013, 40(21):4060-4063.
[20] LI Y. HIF-1α signal pathway related to diabetes brain microvascular disease and intervention research . Luzhou:North Sichuan Medical College, 2013.
[21] YOU Y C. Study on the mechanism of modifield gegenqinlian decoction on microvascular damage and PI3K/AKT/CREB signaling pathway in hippocampus of diabetic rats with cognitive dysfunction . Chengdu:Chengdu University of Traditional Chinese Medicine, 2015.
[22] YAN B, TIAN G Q. Renin-angiotensin system and diabetic cognitive dysfunction, and effects of traditional chinese medicine on them. Chin J Rehabil Theory Pract (中国康复理论与实践), 2017, 23(3):270-273.
[23] WANG W, HE J H. Renin-angiotensin system and liver insulin resistance. Proc Clin Med (临床医药实践), 2016, 25(5):370-373.
[24] LIU B. The protective effects of puerarin on cardiac hypertrophy by activation of autophagy via AMPK/mTOR signal pathway . Guangzhou:Southern Medical University, 2016.
[25] ZHENG S J, CHEN N Q. Advancement in studies on transcription factor FoxO1 in pancreatic β-Cells. Med Recap (医学综述), 2011, 17(1):47-49.
[26] RAO X J. The effect of inhibiting Foxol on the glucose consumption of insulin resistant cells and the mechanism . Zhengzhou:Zhengzhou University, 2009.
[27] LIU Y G, XIE X X, WU J, et al. Research progress on drugs with new targets in treatment of type 2 diabetes. Drugs Clin (现代药物与临床), 2015, 30(2):222-227.
[28] GE B, XIE M L, GU Z L, et al. AMPK acts as a new target for the treatment of type 2 diabetes. Chin Pharmacol Bull (中国药理学通报), 2008, 24(5):580-583.
[29] XIANG X S. Study of type 2 diabetic rat model and its application in the valuation of hypoglycemic functional food . Beijing:Chinese Center for Disease Control and Prevention, 2010.
[30] WANG X Y, WANG Y L, XU W R. Advances in studies on treatment for targets of diabetes mellitus in recent years. Drug Eval Res (药物评价研究), 2012,35(1):42-45.
[31] TU J, LUO X X, LI B T, et al. Effects of berberine on mRNA expression levels of PPAR and adipocytokines in insulin-resistant adipocytes. China J Chin Mater Med (中国中药杂志), 2016, 41(11):1983-1989.
[32] LI B T. The compatibility law and action mechanism study for Gegen Qinlian Decoction(GGQLD) in Type 2 diabetes mellitus . Changsha:Hunan University of Chinese Medicine, 2015.
[33] ZHENG J H. Screening of molecular targets involved in antagonistic effects of natural antioxidants on insulin resistance . Changchun:Jinlin University, 2011.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
河南省高等学校重点科研项目资助(17A360026, 15A350012);河南省科技攻关计划资助(172102310326, 172102310616);新乡医学院博士科研启动基金资助(505095)
{{custom_fund}}
PDF(2872 KB)
