关键词: 网络药理学, 瑞香狼毒, 类风湿性关节炎, 肿瘤坏死因子, 白介素-6, 白介素-1β

Abstract: This work aims to predict and verify the potential mechanism of Stellera chamaejasme L. in the treatment of rheumatoid arthritis(RA)based on network pharmacology. The main chemical components of Stellera chamaejasme L. were obtained from TCMSP, PubMed and TCMID databases and literature mining. The therapeutic targets of Stellera chamaejasme L. were obtained by using Uniprot and- DOI:10.3969/j.issn.1000-1565.2023.01.008基于网络药理学及动物实验探讨瑞香狼毒治疗RA作用机制胡伊力格其^1,2,白小红¹,白梅荣^1,2,包文双¹,胡和珠拉^1,2,拉喜那木吉拉¹(1.内蒙古民族大学 蒙医药学院,内蒙古 通辽 028000;2.内蒙古民族大学 蒙医药研发工程教育部重点实验室,内蒙古 通辽 028000)摘 要:为探讨瑞香狼毒(Stellera chamaejasme L.)治疗类风湿性关节炎(rheumatoid arthritis,RA)的潜在机制,利用TCMSP、PubMed及TCMID数据库和文献挖掘获得瑞香狼毒主要化学成分,利用Swiss Target Prediction、Uniprot数据库获得瑞香狼毒治疗疾病靶点,运用OMIM、GeneCards及PharmGKB数据库获取RA主要作用靶点,通过对化学成分靶点与疾病基因进行交集整合,筛选瑞香狼毒治疗RA的潜在治疗靶点.使用Cytoscape 3.6.1 软件构建“药物-活性成分-靶点-疾病”相互作用网络图,将潜在治疗靶点用DAVID软件分析预测相关的生物学过程,并通过动物实验对主要生物学过程进行验证.采用ELISA检测瑞香狼毒对RA模型大鼠血清炎症因子的影响,该研究共筛选出瑞香狼毒60个活性成分,5 017个与RA潜在治疗靶点及380个交集靶点;动物实验结果表明,瑞香狼毒可以通过抑制炎症因子肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)表达以发挥抗RA作用.该研究揭示了网络药理学预测并指导实验设计的合理性,证实瑞香狼毒可以通过抑制炎症因子以发挥抗RA作用,为瑞香狼毒治疗RA的机制研究提供依据.关键词:网络药理学;瑞香狼毒;类风湿性关节炎;肿瘤坏死因子;白介素-6;白介素-1β中图分类号:R593.21 文献标志码:A 文章编号:1000-1565(2023)01-0048-10Mechanism of Stellera chamaejasme L. in the treatment of reumatoid arthritis based on network pharmacology and animal experiment Huyiligeqi^1,2,BAI Xiaohong¹, BAI Meirong^1,2, BAO Wenshuang¹, Huhezhula^1,2, Laxinamujila¹(1.School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000,China;2.Key Laboratory of Mongolian Medicine Research and Development Engineering of the Ministry of Education, Inner Mongolia Minzu University, Tongliao 028000,China)Abstract: This work aims to predict and verify the potential mechanism of Stellera chamaejasme L. in the treatment of rheumatoid arthritis(RA)based on network pharmacology. The main chemical components of Stellera chamaejasme L. were obtained from TCMSP, PubMed and TCMID databases and literature mining. The therapeutic targets of Stellera chamaejasme L. were obtained by using Uniprot and- 收稿日期:2022-06-20 基金项目:内蒙古自治区自然科学基金资助项目(2018LH08063);内蒙古民族大学中药学(蒙药学)重点学科建设项目(ZYX005);内蒙古民族大学博士科研启动基金资助项目(2017B5408);内蒙古自治区高等学校蒙药安全评价“创新团队”项目(NMGIRT2216);内蒙古自治区自然科学基金资助项目(2020LH08013);蒙药标准化研究国际合作科技创新项目(MDKBZH2018033);蒙医药研发工程教育部重点实验室开发基金项目(MDK2021051);内蒙古自治区卫生健康科技计划项目(202202258) 第一作者:胡伊力格其(1978—),女,蒙古族,内蒙古通辽人,内蒙古民族大学副教授,博士,主要从事蒙药及复方质量标准和药学方面研究.E-mail:b13948550593@163.com第1期胡伊力格其等:基于网络药理学及动物实验探讨瑞香狼毒治疗RA作用机制Swiss Target Prediction databases. Main targets of RA were screened through GeneCards, OMIM and PharmGKB databases. The chemical component targets and disease targets were integrated to screen the potential therapeutic targets of Stellera chamaejasme L. for RA. Cytoscape 3.6.1 software was used to construct the “drug-component-target-disease” interaction network diagram. Meanwhile, potential therapeutic targets were analyzed by DAVID software to predict the relevant biological process. Finally, the main biological processes were verified by animal experiments. The effects of Stellera chamaejasme L. on serum inflammatory factors in RA model rats were detected by ELISA. A total of 60 active components of Stellera chamaejasme L., 5017 potential therapeutic targets and 380 common targets for RA were screened out. The results of animal experiments showed that Stellera chamaejasme L. attenuates RA by inhibiting the expression of inflammatory factors including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and interleukin-6(IL-6). This study revealed the rationality of network pharmacology to predict and guide the experimental design and confirmed that Stellera chamaejasme L. exerted anti-RA effect by inhibiting inflammatory factors, and provided basis for the study of the mechanism of Stellera chamaejasme in treating RA.

Key words: network pharmacology, Stellera chamaejasme L., rheumatoid arthritis, tumor necrosis factor, interleukin-1β, interleukin-6