基于网络药理学探讨昆明山海棠-益母草药对治疗类风湿关节炎的机制

曾丽盈; 王强; 韩隆胤; 钱凯; 杜彦仪; 黄文广; 郭文杰; 史周薇; 刘敏莹; 林昌松

doi:10.13422/j.cnki.syfjx.20191941

您当前的位置：

首页 >

文章列表页 >

基于网络药理学探讨昆明山海棠-益母草药对治疗类风湿关节炎的机制

数据挖掘 | 更新时间：2021-02-09

- 基于网络药理学探讨昆明山海棠-益母草药对治疗类风湿关节炎的机制
- Mechanism of Tripterygium hypoglaucum Radix-Leonurus japonicus Herba for Treating Rheumatoid Arthritis Based on Network Pharmacology
- 中国实验方剂学杂志 2019年25卷第19期页码：170-181
- 作者机构：
  
  1.广州中医药大学，广州　 510006；
  2.广州中医药大学　第一附属医院，广州　 510405
- 作者简介：
  
  曾丽盈，在读硕士，从事中医临床基础及风湿病研究，E-mail：645190497@qq.com
  林昌松，硕士，主任医师，从事风湿病中医药研究，E-mail：1617213793@qq.com
- 基金信息：
  
  国家自然科学基金项目(81573930;81774262);广东省自然科学基金项目(2017A030311009)
- DOI：10.13422/j.cnki.syfjx.20191941
  中图分类号： R2-0; R285.5; R289
- 收稿日期：2019-04-18，
  
  网络出版日期：2019-06-19，
  
  纸质出版日期：2019-10-05
- 稿件说明：
移动端阅览
曾丽盈, 王强, 韩隆胤, 等. 基于网络药理学探讨昆明山海棠-益母草药对治疗类风湿关节炎的机制[J]. 中国实验方剂学杂志, 2019,25(19):170-181.

Li-ying ZENG, Qiang WANG, Long-yin HAN, et al. Mechanism of Tripterygium hypoglaucum Radix-Leonurus japonicus Herba for Treating Rheumatoid Arthritis Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 170-181.
曾丽盈, 王强, 韩隆胤, 等. 基于网络药理学探讨昆明山海棠-益母草药对治疗类风湿关节炎的机制[J]. 中国实验方剂学杂志, 2019,25(19):170-181. DOI： 10.13422/j.cnki.syfjx.20191941.

Li-ying ZENG, Qiang WANG, Long-yin HAN, et al. Mechanism of Tripterygium hypoglaucum Radix-Leonurus japonicus Herba for Treating Rheumatoid Arthritis Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(19): 170-181. DOI： 10.13422/j.cnki.syfjx.20191941.

摘要

目的：

运用计算机网络药理学技术筛选昆明山海棠-益母草药对治疗RA的的主要活性成分，预测活性成分的作用靶点，建立药物成分-活性成分-作用靶点网络，进一步探讨昆明山海棠-益母草药对治疗类风湿关节炎(RA)的潜在作用机制。

方法：

通过DisGeNET，TTD，Drugbank数据库收集RA疾病作用靶点；从中药系统药理学分析平台(TCMSP)获得昆明山海棠、益母草的潜在活性成分及其对应的靶点；使用ImageGP平台筛选药物与疾病共有靶点；使用String数据库构建共有靶点互作(PPI)网络模型；采用Cytoscape软件建立“药物-活性成分-关键作用靶点”网络；采用String数据库构建蛋白质相互作用网络；利用ClueGO插件对靶点进行基因功能(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。

结果：

通过筛选得到9个药物活性成分，共涉及235个作用靶点，与疾病靶点有关的活性成分为7个，得到昆明山海棠-益母草药对-疾病共同靶点24个，共同靶点主要富集于278个生物过程和141条信号通路上发挥治疗RA的作用。

结论：

昆明山海棠-益母草药对对RA的治疗作用体现了中药多成分-多靶点-多途径的特点，为阐释其治疗RA的作用机制与临床应用提供了科学依据。

Abstract

Objective:

Computer network pharmacology technology was used to screen the main active ingredients of

Tripterygium hypoglaucum

radix-

Leonurus japonicus

herba for the treatment of rheumatoid arthritis(RA)

predict the targets of the active ingredients

establish a pharmaceutical ingredient-active ingredient-target network

and further explore the potential mechanism of

Tripterygium hypoglaucum

radix-

Leonurus japonicus

herba for the treatment of RA.

Method:

RA disease targets were collected through DisGeNET

TTD

and Drugbank databases

the potential active components of

Tripterygium hypoglaucum

radix and

Leonurus japonicus

herba and their corresponding targets were obtained from the Chinese Medicine System Pharmacology Analysis Platform (TCMSP); common targets for drugs and diseases were screened by using the ImageGP platform; a common target interaction (PPI) network model was constructed by using the String database

a " drug-active ingredient-key target" network was constructed by using Cytoscape software

a protein interaction network was constructed by using the String database

gene function (GO) analysis and pathway enrichment analysis based on the Kyoto Gene and Genomic Encyclopedia (KEGG) were performed by using the ClueGO plug-in.

Result:

Through screening

9 active pharmaceutical ingredients were obtained

involving a total of 235 targets

and 7 active ingredients were related to the disease targets. 24 common targets for

Tripterygium hypoglaucum

radix

Leonurus japonicus

herba-disease were obtained. The common targets were mainly enriched in 278 biological processes and 141 signaling pathways to play a role in the treatment of RA.

Conclusion:

The therapeutic effect of

Tripterygium hypoglaucum

radix

Leonurus japonicus

herba on RA reflects the characteristics of multi-component-multi-target-multi-channel of traditional Chinese medicine

and provides a scientific basis for explaining its mechanism and clinical application of RA.

关键词

Keywords

references

Chaudhari K , Rizvi S , Syed B A . Rheumatoid arthritis: current and future trends [J]. Nat Rev Drug Discov , 2016 , 15 ( 5 ): 305 - 306 .

Mcinnes I B , Schett G . The pathogenesis of rheumatoid arthritis [J]. N Engl J Me , 2011 , 365 ( 23 ): 2205 - 2219 .

Harnden K , Pease C , Jackson A . Rheumatoid arthritis [J]. BMJ , 2016 , 352 : i387 .

Aletaha D , Smolen J S . Diagnosis and management of rheumatoid arthritis: a review [J]. JAMA , 2018 , 320 ( 13 ): 1360 - 1372 .

Burmester G R , Pope J E . Novel treatment strategies in rheumatoid arthritis [J]. Lancet , 2017 , 389 ( 10086 ): 2338 - 2348 .

Miossec I P . Drug treatments for rheumatoid arthritis: looking backwards to move forwards [J]. BMJ , 2015 , 350 : h1192 .

徐佳琦，周寅敏．类风湿性关节炎的中医药治疗效果研究进展 [J]．世界最新医学信息文摘， 2018 ， 18 ( A2 )： 121 - 125 ．

林昌松，陈秀敏，林云斌．昆母汤佐治活动性类风湿关节炎的临床效果 [J]．广东医学， 2013 ， 34 ( 16 )： 2580 - 2582 ．

林昌松，梁江，刘风震，等．断藤益母汤治疗类风湿关节炎的临床疗效观察 [J]．广州中医药大学学报， 2012 ， 29 ( 6 )： 632 - 637 ．

谢晨琼，周萍，李祥，等．昆明山海棠化学成分及药理作用和临床应用研究进展 [J]．中草药， 2015 ， 46 ( 13 )： 1996 - 2010 ．

叶林虎，贺梅，赵欣黔，等．益母草及其制剂的研究进展 [J]．中国民族民间医药， 2019 ， 28 ( 2 )： 56 - 60 ．

陈秀敏，林昌松，刘清平，等．昆母汤对类风湿关节炎滑膜细胞增殖及凋亡的影响 [J]．实用医学杂志， 2015 ， 31 ( 17 )： 2793 - 2796 ．

林昌松，林云斌，陈秀敏，等．昆母汤醇提取物对类风湿关节炎成纤维样滑膜细胞增殖及IL-1β和MMP-3表达的影响 [J]．广东医学， 2015 ， 36 ( 14 )： 2136 - 2138 ．

林昌松，陈秀敏，林云斌，等．昆母汤醇提液对人类风湿关节炎成纤维样滑膜细胞凋亡及caspase-3表达的影响 [J]．广东医学， 2015 ， 36 ( 3 )： 339 - 341 ．

蔡叙东，林昌松，潘东梅，等．断藤益母汤对破骨细胞RANKL信号通路及MMP-9的影响 [J]．中国实验方剂学杂志， 2018 ， 24 ( 12 )： 68 - 73 ．

蔡叙东，林昌松，潘东梅，等．断藤益母汤对破骨细胞活性及Wnt信号通路的影响研究 [J]．中华中医药学刊， 2018 ， 36 ( 10 )： 2332 - 2335 ．

潘东梅，王强，蔡叙东，等．断藤益母汤抑制PI3K/AKT通路诱导类风湿关节炎成纤维样滑膜细胞凋亡 [J]．中华中医药杂志， 2018 ， 33 ( 5 )： 2051 - 2055 ．

LI N , XU Q , LIU Q , et al . Leonurine attenuates fibroblast-like synoviocyte-mediated synovial inflammation and joint destruction in rheumatoid arthritis [J]. Rheumatology (Oxford) , 2017 , 56 ( 8 ): 1417 - 1427 .

PAN D , LI N , LIU Y , et al . Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway [J]. Int Immunopharmacol , 2018 , 55 : 174 - 182 .

Hopkins A L . Network pharmacology: the next paradigm in drug discovery [J]. Nat Chem Biol , 2008 , 4 ( 11 ): 682 - 690 .

Pinero J , Bravo à , Queralt-Rosinach N , et al . DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants [J]. Nucleic Acids Res , 2017 , 45 ( D1 ): D833 - D839 .

CHEN X , JI Z L , CHEN Y Z . TTD: therapeutic target database [J]. Nucleic Acids Res , 2002 , 30 ( 1 ): 412 - 415 .

Wishart D S , Feunang Y D , GUO A C , et al . DrugBank 5.0: a major update to the DrugBank database for 2018 [J]. Nucleic Acids Res , 2018 , 46 ( D1 ): D1074 - D1082 .

RU J , LI P , WANG J , et al . TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform , 2014 , 6 : 13 .

Szklarzyk D , Morris J H , Cook H , et al . The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible [J]. Nucleic Acids Res , 2017 , 45 ( D1 ): D362 - D368 .

Cline M S , Smoot M , Cerami E , et al . Integration of biological networks and gene expression data using Cytoscape [J]. Nat Protoc , 2007 , 2 ( 10 ): 2366 - 2382 .

YANG Y , YE Y , QIU Q , et al . Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway [J]. Int Immunopharmacol , 2016 , 41 : 8 - 16 .

XU H , ZHAO H , LU C , et al . Triptolide inhibits osteoclast differentiation and bone resorption in vitro via enhancing the production of IL-10 and TGF-β1 by regulatory T cells [J]. Mediators Inflamm , 2016 , doi: 10.1155/2016/8048170 http://doi.org/10.1155/2016/8048170 .

LIU C , ZHANG Y , KONG X , et al . Triptolide prevents bone destruction in the collagen-induced arthritis model of rheumatoid arthritis by targeting RANKL/RANK/OPG signal pathway [J]. Evid Based Complement Alternat Med , 2013 , doi: 10.1155/2013/626038 http://doi.org/10.1155/2013/626038 .

Lee C J , Moon S J , Jeong J H , et al . Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 signaling axis prevents the development of rheumatoid arthritis [J]. Cell Death Dis , 2018 , 9 ( 3 ): 401 .

Yoon H Y , Lee E G , Lee H , et al . Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs [J]. Int J Mol Med , 2013 , 32 ( 4 ): 971 - 977 .

Choi E J , Bae S C , YU R , et al . Dietary vitamin E and quercetin modulate inflammatory responses of collagen-induced arthritis in mice [J]. J Med Food , 2009 , 12 ( 4 ): 770 - 775 .

Kim H R , Kim B M , Won J Y , et al . Quercetin, a plant polyphenol, Has potential for the prevention of bone destruction in rheumatoid arthritis [J]. J Med Food , 2019 , 22 ( 2 ): 152 - 161 .

YANG Y , ZHANG X , XU M , et al . Quercetin attenuates collagen-induced arthritis by restoration of Th17/Treg balance and activation of Heme Oxygenase 1-mediated anti-inflammatory effect [J]. Int Immunopharmacol , 2018 , 54 : 153 - 162 .

JI J J , LIN Y , HUANG S S , et al . Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis [J]. Afr J Tradit Complement Altern Med , 2013 , 10 ( 3 ): 418 - 421 .

PAN F , ZHU L , LV H , et al . Quercetin promotes the apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by upregulating lncRNA MALAT1 [J]. Int J Mol Med , 2016 , 38 ( 5 ): 1507 - 1514 .

LIN J , HUO R , XIAO L , et al . A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis [J]. 2014 , 66 ( 1 ): 49 - 59 .

ZHANG T , LI H , SHI J , et al . p53 predominantly regulates IL-6 production and suppresses synovial inflammation in fibroblast-like synoviocytes and adjuvant-induced arthritis [J]. Arthritis Res Ther , 2016 , 18 ( 1 ): 271 .

Park J S , Lim M A , Cho M L , et al . p53 controls autoimmune arthritis via STAT-mediated regulation of the Th17 cell/Treg cell balance in mice [J]. Arthritis Rheum , 2013 , 65 ( 4 ): 949 - 959 .

XIAO P , HAO Y , ZHU X , et al . p53 contributes to quercetin-induced apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes [J]. Inflammation , 2013 , 36 ( 2 ): 272 - 278 .

Park K H , GU D R , JIN S H , et al . Pueraria lobate inhibits RANKL-mediated osteoclastogenesis via downregulation of CREB/PGC1β/c-Fos/NFATc1 signaling [J]. Am J Chin Med , 2017 , 45 ( 8 ): 1725 - 1744 .

Choi B Y , Park C H , NA Y H , et al . Inhibition of RANKL-induced osteoclast differentiation through the downregulation of c-Fos and NFATc1 by eremochloa ophiuroides (centipedegrass) extract [J]. Mol Med Rep , 2016 , 13 ( 5 ): 4014 - 4022 .

SHANG W , ZHAO L J , DONG X L , et al . Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways [J]. Mol Med Rep , 2016 , 14 ( 4 ): 3620 - 3626 .

Kim H J , Yoon K A , Lee M K , et al . A novel small molecule, NecroX-7, inhibits osteoclast differentiation by suppressing NF-κB activity and c-Fos expression [J]. Life Sci , 2012 , 91 ( 19/20 ): 928 - 934 .

唐敏，何成松．丝裂原活化蛋白激酶信号转导通路与类风湿关节炎关系的研究 [J]．现代医药卫生， 2014 ， 30 ( 8 )： 1203 - 1206 ．

王洁，卞莹莹，张川，等．肿瘤坏死因子及其受体在类风湿性关节炎中的研究进展 [J]．药学实践杂志， 2017 ， 35 ( 4 )： 289 - 293 ．

刘丽丽，毛艳艳，高柳滨．类风湿关节炎全球药物研发状况分析 [J]．科技导报， 2016 ， 34 ( 24 )： 44 - 55 ．

Macdonald I J , LIU S C , SU C M , et al . Implications of angiogenesis involvement in arthritis [J]. Int J Mol Sci , 2018 , 19 ( 7 ): 2012 .

XIA Z B , MENG F R , FANG Y X , et al . Inhibition of NF-κB signaling pathway induces apoptosis and suppresses proliferation and angiogenesis of human fibroblast-like synovial cells in rheumatoid arthritis [J]. Medicine , 2018 , 97 ( 23 ): e10920 .

Girdharan S , Srinivasan M . Mechanisms of NF-κB p65 and strategies for therapeutic manipulation [J]. J Inflamm Res , 2018 , 11 : 407 - 419 .

SUN W , QIN R , WANG R , et al . Sam68 promotes invasion, migration, and proliferation of fibroblast-like synoviocytes by enhancing the NF-κB/P65 Pathway in rheumatoid arthritis [J]. Inflammation , 2018 , 41 ( 5 ): 1661 - 1670 .

Vasarhel B , Meszaros K , Karvaly G , et al . Focusing on tissue biomarkers. Estrogens as key players in the immune response and autoimmunity [J]. Orv Hetil , 2015 , 156 ( 51 ): 2070 - 2076 .

Paulissen S M , van Hamburg J P , Davelaar N , et al . Synovial fibroblasts directly induce Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23 [J]. J Immunol , 2013 , 191 ( 3 ): 1364 - 1372 .

YAN Y , Singh G K , ZHANG F , et al . Comparative study of normal and rheumatoid arthritis fibroblast-like synoviocytes proliferation under cyclic mechanical stretch: role of prostaglandin E2 [J]. Connect Tissue Res , 2012 , 53 ( 3 ): 246 - 254 .

Kim Y K , Shin J S , Nahm M H . NOD-like receptors in infection, immunity, and diseases [J]. Yonsei Med J , 2016 , 57 ( 1 ): 5 - 14 .

Lim K H , Staudt L M . Toll-like receptor signaling [J]. Cold Spring Harb Perspect Biol , 2013 , 5 ( 1 ): a11247 .

LIN Y , LUO Z . Aberrant methylation patterns affect the molecular pathogenesis of rheumatoid arthritis [J]. Int Immunopharmacol , 2017 , 46 : 141 - 145 .

Molino S , Tate E , Mckillop W M , et al . Sphingolipid pathway enzymes modulate cell fate and immune responses [J]. Immunotherapy , 2017 , 9 ( 14 ): 1185 - 1198 .

Redelman D , Welniak L A , Taub D , et al . Neuroendocrine hormones such as growth hormone and prolactin are integral members of the immunological cytokine network [J]. Cell Immunol , 252 ( 1/2 ): 111 - 121 .

TANG C , LI Y , LIN X , et al . Prolactin increases tumor necrosis factor alpha expression in peripheral CD14 monocytes of patients with rheumatoid arthritis [J]. Cell Immunol , 2014 , 290 ( 1 ): 164 - 168 .

Taylor C T , Colgan S P . Regulation of immunity and inflammation by hypoxia in immunological niches [J]. Nat Rev Immunol , 2017 , 17 ( 12 ): 774 - 785 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基于网络药理学探讨五苓散治疗类风湿关节炎的作用机制

基于网络药理学的五子衍宗丸抗睾丸炎症作用机制

基于网络药理学的附子-干姜药对治疗心力衰竭的作用机制分析

中药干预类风湿关节炎相关信号通路研究进展

基于网络药理学的鹿茸治疗骨关节炎作用的机制