摘要
目的基于系统药理学方法研究雷公藤配伍甘草治疗类风湿性关节炎作用机制。方法基于中药系统药理学平台(TCMSP)数据库和文献搜索,建立雷公藤配伍甘草化学成分库。运用DRAR-CPI、中医分子机制的生物信息学分析工具(BATMAN-TCM)等在线预测网站,预测成分靶标,并与疾病靶标取交集得到雷公藤配伍甘草治疗类风湿性关节炎作用靶标。通过作用靶标反向筛选潜在活性成分,并用超高效液相色谱-飞行时间质谱(UPLC-Q-TOF/MS)分析手段对活性成分进行验证。利用GeneMANIA数据库搜索间接靶标并利用蛋白互作筛选关键靶标,采用分子对接技术(SystemsDock)对潜在活性成分和关键靶标进行匹配,验证前期靶标筛选的可靠性以及反向药效团匹配的正确性。通过GO和京都基因与基因组百科全书通路分析(KEGG)生物学注释分析关键作用通路,探讨雷公藤配伍甘草治疗类风湿性关节炎作用机制。结果共得到33个化学成分和47个潜在靶标,其中32个成分31个靶标和35条通路与药对治疗类风湿性关节炎有密切关系,主要涉及花生四烯酸代谢通路、白介素(IL)-17信号通路、核因子(NF)-κB信号通路等炎症通路以及T细胞受体信号通路、C型凝集素受体信号通路等与免疫相关的通路。结论雷公藤配伍甘草治疗类风湿性关节炎主要通过炎症与免疫调节等多条途径得以实现。
Objective To explore the mechanism of Triptergium wilfordii combined with Glycyrrhiza uralensis in the treatment of Rheumatoid Arthritis based on systematic pharmacology.Methods TCMSP database and literature search were used to establish the chemical constituents Library of Triptergium wilfordii combined with Glycyrrhiza uralensis.The target of components was predicted through DRAR-CPI,BATMAN-TCM and other online prediction websites,and intersect with disease targets to obtain the therapeutic targets of Triptergium wilfordii combined with Glycyrrhiza uralensis for Rheumatoid Arthritis.Potential active components were screened by reverse targeting and verified by ultra-high performance liquid chromatography-time-of-flight mass spectrometry(UPLC-Q-TOF/MS).GeneMANIA database was used to search indirect targets and protein interaction was used to screen key targets.Molecular docking technology(Systems Dock)was used to match potential active ingredients with key targets to verify the reliability of previous target screening and the correctness of reverse pharmacophore matching.To explore the mechanism of Triptergium wilfordii combined with Glycyrrhiza uralensis in the treatment of rheumatoid arthritis,key pathways were analyzed by GO and KEGG biological annotations.Results A total of 33 chemical constituents and 47 potential targets were obtained.Among them,31 targets of 32 components and 35 pathways were closely related to drug therapy for Rheumatoid Arthritis,mainly involving the inflammatory pathways such as arachidonic acid metabolic pathway,IL-17 signaling pathway,as well as the immune-related pathways such as NF-κB signaling pathway and T cell receptor signaling pathway.Conclusion The treatment of Triptergium wilfordii combined with Glycyrrhiza uralensis mainly through inflammation and immune regulation.
作者
陈瑾
刘传鑫
杨培
曾琪
陈敏
雷仲夏
詹雪艳
CHEN Jin;LIU Chuanxin;YANG Pei;ZENG Qi;CHEN Min;LEI Zhongxia;ZHAN Xueyan(School of Chinese Pharmacy,Beijing University of Chinese Medicine,Beijing 10029,China)
出处
《药物评价研究》
CAS
2019年第9期1705-1722,共18页
Drug Evaluation Research
关键词
雷公藤
甘草
类风湿性关节
系统药理学
靶点
通路
机制
Triptergium wilfordii Hook.F
Glycyrrhiza uralensis
Rheumatoid Arthritis
systemic pharmacology
targets
pathways
mechanism
