基于网络药理学探究中药黄连抗菌作用机制

doi:10.16431/j.cnki.1671-7236.2020.05.034

摘要/Abstract

摘要： 试验旨在基于网络药理学方法探究中药黄连主要活性成分的抗菌作用机制。从TCMSP数据库筛选黄连有效成分及作用靶点，利用Uniprot数据库转化成相应靶点基因，将活性成分和靶点基因导入Cytoscape 3.6.1软件，构建活性成分-靶点网络图。再结合GeneCards数据库检索黄连抗菌相关靶点，将核心靶点基因上传至STRING平台，构建蛋白相互作用网络，最后，利用DAVID数据库对关键靶点进行GO生物学过程分析和KEGG通路富集分析。结果显示，黄连9种有效成分作用于105个抗菌靶点参与22条生物学过程（生物过程18条、分子功能3条、细胞组成1条）和19条相关信号通路。其中黄连的主要有效成分为槲皮素、氢化小檗碱、氧化小檗碱、小檗碱和巴马汀等；抗菌作用靶点为IL2、VCAM1、STAT1、NOS2、TGFB1、CASP9、MMP1、NFKBIA和CXCL10等；参与的生物学过程主要包括炎症反应、RNA聚合酶Ⅱ启动子转录的正调节、对脂多糖的反应、凋亡过程的负调节、细胞黏附等；主要作用于Toll样受体信号通路、肿瘤坏死因子（TNF）信号通路、NF-κB信号通路等。本试验结果表明，黄连可能通过槲皮素、小檗碱、巴马汀等活性成分作用于IL2、VCAM1、STAT1等关键靶标参与Toll样受体信号通路、TNF信号通路联合发挥抗菌作用，充分体现了黄连多成分、多靶点、多通路的抗菌作用机制，为进一步深入阐明黄连抗菌机制提供理论参考。

关键词: 网络药理学; 黄连; 抗菌; 作用机制

Abstract: This study was aimed to explore the antibacterial mechanism of the main components of Chinese traditional medicine Coptidis Rhizoma based on network pharmacology.The effective components and target targets of Coptidis Rhizoma were screened from the TCMSP database,and the corresponding target genes were transformed using the Uniprot database.The active components and target genes were imported into the Cytoscape 3.6.1 software to construct an active component-target network diagram.Combined with the GeneCards database to search the antibacterial related targets of Coptidis Rhizoma,the core target genes were uploaded to the STRING platform to build a protein interaction network.Finally,the DAVID database was used to analyze key targets by GO biological processes and KEGG pathway enrichment.The results of network pharmacology showed that 9 effective components of Coptidis Rhizoma acted on 105 antibacterial targets and participated in 22 biological processes (18 biological processes,3 molecular functions,1 cell composition) and 19 related signal pathways.Among them,the main active ingredients of Coptidis Rhizoma were quercetin,(R)-Canadine,berlambine,berberine and palmatine,etc.Antibacterial targets were IL2,VCAM1,STAT1,NOS2,TGFB1,CASP9,MMP1,NFKBIA and CXCL10,etc.The involved biological processes mainly included inflammatory response,positive regulation of RNA polymerase Ⅱ promoter transcription,response to lipopolysaccharide,negative regulation of apoptotic process,cell adhesion,etc.Mainly act on Toll-like receptors signal pathway,TNF signal pathway,NF-kappa B signaling pathway,etc.Coptidis Rhizoma might through its active ingredients such as quercetin,berberine,palmatine act on other key targets such as IL2,VCAM1 and STAT1 to participate in the Toll-like receptor signaling pathway and TNF signaling pathway to exert antibacterial effect.It fully reflected the antibacterial action mechanism of Coptidis Rhizoma with multiple components,multiple targets and multiple pathways,and provided a theoretical reference for further clarifying the antibacterial mechanism of Coptidis Rhizoma.

Key words: network pharmacology; Coptidis Rhizoma; antibacterial; mechanism

中图分类号:

S853.74

姚姗姗, 刘静茹, 陈静, 张鹏, 王文静, 张铁, 王春光. 基于网络药理学探究中药黄连抗菌作用机制[J]. 中国畜牧兽医, 2020, 47(5): 1593-1601.

YAO Shanshan, LIU Jingru, CHEN Jing, ZHANG Peng, WANG Wenjing, ZHANG Tie, WANG Chunguang. Study on Anti-bacterial Mechanism of Coptidis Rhizoma Based on Network Pharmacology[J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(5): 1593-1601.

参考文献

[1] 李彩虹,周克元.黄连活性成分的作用及机制研究进展[J].时珍国医国药,2010,21(2):466-468. LI C H,ZHOU K Y.Study advances on the effects and mechanisms of active constituents of Coptidis Rhizoma[J].Lishizhen Medicine and Materia Medica Research,2010,21(2):466-468.(in Chinese)
[2] 王丽.黄连碱对内毒素发热大鼠解热、抗炎作用的PK-PD模型研究[D].成都:成都中医药大学,2018. WANG L.Pharmacokinetic-pharmacodynamic study on antipyretic effects and anti-inflammatory of coptisine on endotoxin-induced pyrexia of rats[D].Chengdu:Chengdu University of TCM,2018.(in Chinese)
[3] 张庆莲,黄娟,邵单炫,等.黄连抗菌作用研究进展[J].中医药信息,2019,36(5):125-127. ZHANG Q L,HUANG J,SHAO D X,et al.Research progress on antibacterial activity of Coptis chinensis[J].Information on Traditional Chinese Medicine,2019,36(5):125-127.(in Chinese)
[4] 张潇,张亚丽,苗祥贞,等.黄连不同炮制品及组分的抗肿瘤活性与6种生物碱含量相关性研究[J].中华中医药杂志,2019,34(6):2668-2671. ZHANG X,ZHANG Y L,MIAO X Z,et al.Study on the correlation of antitumor activity and the content 6 alkaloids of different processed products and components of Rhizoma coptidis based on Caenorhabditis elegans[J].China Journal of Traditional Chinese Medicine and Pharmacy,2019,34(6):2668-2671.(in Chinese)
[5] 赵亚丽.黄连素通过miR-204/SIRT1改善糖尿病胰岛β细胞功能损伤的作用机制研究[D].长春:吉林大学,2019. ZHAO Y L.Berberine improves diabetic B cell damage through miR-204/SIRT 1 signaling pathway[D].Changchun:Jilin University,2019.(in Chinese)
[6] TANG J,FENG Y,TSAO S,et al.Berberine and Coptidis Rhizoma as novel antineoplastic agents:A review of traditional use and biomedical investigations[J].Journal of Ethnopharmacology,2009,126(1):5-17.(in Chinese)
[7] 林媛,司书毅,蒋建东.小檗碱的抗菌作用[J].药学学报,2018,53(2):163-168. LIN Y,SI S Y,JIANG J D.Antibacterial activity of berberine[J].Acta Pharmaceutica Sinica,2018,53(2):163-168.(in Chinese)
[8] 刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,47(6):696-703. LIU Z H,SUN X B.Network pharmacology:New opportunity for the modernization of traditional Chinese medicine[J].Acta Pharmaceutica Sinica,2012,47(6):696-703.(in Chinese)
[9] METZ J T,PHILIP J H.Rational approaches to targeted polypharmacology:Creating and navigating protein-ligand interaction networks[J].Current Opinion in Chemical Biology,2010,14(4):498-504.
[10] 孙莉敏,刘丽芳,朱华旭,等.基于网络药理学的黄连解毒汤治疗阿尔兹海默症的作用机制研究[J].药学学报,2017,52(8):1268-1275. SUN L M,LIU L F,ZHU H X,et al.Network pharmacology-based study on intervention mechanism of Huanglian Jiedu decoction in the treatment of Alzheimer's disease[J].Acta Pharmaceutica Sinica,2017,52(8):1268-1275.(in Chinese)
[11] XU X,ZHANG W,HUANG C,et al.A novel chemometric method for the prediction of human oral bioavailability[J].International Journal of Molecular Sciences,2012,13(6):6964-6982.
[12] 汝锦龙.中药系统药理学数据库和分析平台的构建和应用[D].杨凌:西北农林科技大学,2015. RU J L.Construction and utilization of traditional Chinese medicine systems pharmacology database and analysis platform[D].Yangling:Northwest A&F University,2015.(in Chinese)
[13] 田会东,郭丽娜,王单单,等.三七主要活性成分作用机制的网络药理学研究[J].药物评价研究,2019,42(1):70-75. TIAN H D,GUO L N,WANG D D,et al.Investigating the main components and mechanism of Panax notoginseng based on pharmacology network[J].Drug Evaluation Research,2019,42(1):70-75.(in Chinese)
[14] 段凯旋,李跃文,刘和波,等.基于网络药理学的羌活-独活药对抗炎作用机制研究[J].中国药房,2019,30(9):1241-1246. DUAN K X,LI Y W,LIU H B,et al.Study on anti-inflammatory mechanism of couplet medicine of Notopterygium incisum Angelica pubescens based on network pharmacology[J].China Pharmacy,2019,30(9):1241-1246.(in Chinese)
[15] 王维琪.黄连有效成分的药理研究与进展[J].中医临床研究,2016,8(26):147-148. WANG W Q.A review on pharmacologic effects of effective ingredients in Huanglian[J].Clinical Journal of Chinese Medicine,2016,8(26):147-148.(in Chinese)
[16] 谢川东,文燕,曾昱伟,等.黄连抗菌活性成分研究[J].湖北农业科学,2018,57(23):85-88. XIE C D,WEN Y,ZENG Y W,et al.Antibacterial activity component of Coptis chinensis Franch[J].Hubei Agricultural Sciences,2018,57(23):85-88.(in Chinese)
[17] 马莉,陶红莉,关建军,等.槲皮素对中脑动脉闭塞模型大鼠异常自噬和氧化应激的调节作用[J].中药药理与临床,2019,35(4):48-53. MA L,TAO H L,GUAN J J,et al.Regulatory effect of quercetin on abnormal autophagy and oxidative stress in rats with middle cerebral artery occlusion[J].Pharmacology and Clinics of Chinese Materia Medica,2019,35(4):48-53.(in Chinese)
[18] 任改艳,张步有,黄剑林.槲皮素对LPS诱导小鼠RAW264.7细胞炎症的保护作用[J].中成药,2019,41(8):1795-1799. REN G Y,ZHANG B Y,HUANG J L.Protective effects of quercetin on the inflammation of mice RAW264.7 cells induced by LPS[J].Chinese Traditional Patent Medicine,2019,41(8):1795-1799.(in Chinese)
[19] 杨扬,郭举.具有抗肿瘤活性的槲皮素衍生物研究进展[J].中草药,2018,49(6):1468-1475. YANG Y,GUO J.Research progress on active quercetin derivatives with antitumor effect Chinese traditional and herbal drugs[J].Chinese Traditional and Herbal Drugs,2018,49(6):1468-1475.(in Chinese)
[20] 李棒棒.槲皮素对金黄色葡萄球菌Coa抑制作用与机制研究[D].长春:吉林大学,2018. LI B B.Study on the inhibitory effect and mechanism of quercetin on Staphylococcus aureus Coa[D].Changchun:Jilin University,2018.(in Chinese)
[21] 滕楠.槲皮素抑菌作用的体内和体外研究[D].哈尔滨:东北农业大学,2015. TENG N.Bacteriostasis of quercetin in vivo and in vitro[D].Harbin:Northeast Agricultural University,2015.(in Chinese)
[22] 华国强.小檗碱抑菌特点及抑菌机制的初步研究[D].济南:山东大学,2005. HUA G Q.Preliminary study on antibacterial characteristics and mechanism of berberine[D].Jinan:Shandong University,2005.(in Chinese)
[23] 陈太杰,夏文品,周金雁,等.巴马亭的合成[J].中国医药工业杂志,2010,41(7):494-495. CHEN T J,XIA W P,ZHOU J Y,et al.Synthesis of palmatine[J].Chinese Journal of Pharmaceuticals,2010,41(7):494-495.(in Chinese)
[24] 金玉晶,曹大明,赵喜新,等.针灸对CTX化疗小鼠骨髓组织黏附分子ICAM-1、VCAM-1蛋白表达的影响[J].中医学报,2013,28(12):1840-1842. JIN Y J,CAO D M,ZHAO X X,et al.Influence of acupuncture and moxibustion on bone marrow tissue adhesion molecule ICAM-1,VCAM-1 protein expression in post chemotherapy with CTX mice[J].China Journal of Chinese Medicine,2013,28(12):1840-1842.(in Chinese)
[25] KABEL A M,ESTFANOUS R S,ALROBAIAN M M.Targeting oxidative stress,proinflammatory cytokines,apoptosis and toll like receptor 4 by empagliflozin to ameliorate bleomycin-induced lung fibrosis[J].Respiratory Physiology & Neurobiology,2019,273:103316.
[26] YIN Q Y,ZHAO B,QIU Y Y,et al.Research progress of mechanisms and drug therapy for atherosclerosis on Toll-like receptor pathway[J].Journal of Cardiovascular Pharmacology,2019,74(5):379-388.
[27] MONTFORT A,COLACIOS C,LEVADE T,et al.The TNF paradox in cancer progression and immunotherapy[J].Frontiers in Immunology,2019,10:1818.