摘要
目的:基于分子对接与网络药理学探究豨桐丸治疗类风湿性关节炎(rheumatoid arthritis, RA)的潜在生物学机制。方法:运用中药系统药理学数据库与分析平台结合文献挖掘,收集豨桐丸所含有的活性成分,并进行口服利用率、血脑屏障透过率和药物相似性等参数筛选;选择与RA相关的靶蛋白建立受体分子库;应用分子对接进行药物成分的初步筛选并通过50 ns的分子动力学验证对接结果的可靠性;通过化学成分靶点预测和靶点注释,采用Cytoscape 3.6.1软件进行活性成分靶点网络和靶点-疾病网络的构建及拓扑分析,验证了重要的成分与靶点;运用DAVID数据库对豨桐丸的靶点进行GO分析和KEGG富集分析。结果:豨桐丸中化学成分豆甾醇、羽扇醇、谷甾醇、芹菜素-7-O-β-D-葡萄糖醛酸苷丁酯主要通过疏水作用与相关靶蛋白结合发挥药效;豨桐丸治疗RA的机制涉及细胞过程、炎症反应过程等生物过程,涉及细胞膜、突触前膜、膜筏等细胞组分,白蛋白、肿瘤坏死因子、血管内皮生长因子A、丝裂原激活的蛋白激酶、前列腺素G/H合成酶2等多种物质;涉及的信号通路有神经活性配体受体相互作用通路、癌症蛋白多糖通路、人巨细胞病毒感染通路、JAK信号通路、乙肝通路等。结论:豨桐丸治疗RA的分子机制可能是通过多成分、多靶点、多通路的协同作用来发挥疗效,其主要生物学机制可能与神经活性配体-受体相互作用等信号通路有关,这为豨桐丸的推广及RA新药的研发奠定了研究基础。
Objective: To explore the potential biological mechanism of the treatment of rheumatoid arthritis(RA) based on molecular docking and network pharmacology.Methods: TCMSP database combined with literature mining was used to collect the active components contained in Xitong Pill, and screen the parameters such as oral utilization rate, blood-brain barrier permeability and drug similarity;the target proteins related to RA were selected to establish the receptor molecular library;molecular docking was used for preliminary screening of drug components, and the reliability of docking results was verified by 50 ns molecular dynamics;target prediction and target annotation were conducted by chemical composition;Cytoscape 3.6.1 software was used to construct and analyze the active ingredient target network and target disease network, and the important ingredients and targets were verified;DAVID database was used for GO analysis and KEGG enrichment analysis of the target of Xitong Pill.Results: The chemical constituents of stigmasterol, lupinol, sitosterol, and apigenin-7-O-β-D-glucuronide butyl ester in Xitong Pill mainly exert their medicinal effects by binding to related target proteins through hydrophobic interaction;the mechanism of Xitong Pill in treating RA involves biological processes such as cellular process and inflammatory reaction process, cell components such as cell membrane, presynaptic membrane and membrane raft, albumin, tumor necrosis factor, vascular endothelial growth factor A,mitogen activated protein kinase, prostaglandin G/H synthase 2 and so on;the signaling pathways involved include neuroactive ligand receptor interaction pathway, cancer protein polysaccharide pathway, human cytomegalovirus infection pathway, JAK signaling pathway, hepatitis B virus pathway and so on.Conclusion: The molecular mechanism of Xitong Pill in the treatment of RA may be the synergistic effect of multiple components, multiple targets and multiple pathways.Its main biological mechanism may be related to the signal pathways such as neuroactive ligand receptor interaction, which lays a research foundation for the promotion of Xitong Pill and the research and development of new drugs for RA.
作者
庄严
王少佩
王永林
胡玉龙
仝艳
董春红
李晓飞
ZHUANG Yan;WANG Shaopei;WANG Yonglin;HU Yulong;TONG Yan;DONG Chunhong;LI Xiaofei(Henan University of Chinese Medicine,Zhengzhou Henan China 450046)
出处
《中医学报》
CAS
2021年第9期1992-2004,共13页
Acta Chinese Medicine
基金
河南省科技攻关计划项目(082102310028)。
关键词
豨桐丸
类风湿性关节炎
活性物质
分子对接
分子动力学
网络药理学
Xitong Pill
rheumatoid arthritis(RA)
active substances
molecular docking
molecular dynamics
network pharmacology
作者简介
庄严(1994-),女,河南平顶山人,硕士研究生,主要从事药物化学研究;通信作者:李晓飞(1979-),男,河南鲁山人,理学硕士,副教授,主要从事计算机辅助药物设计研究。E-mail:lixiaofei@hactcm.edu.cn;董春红(1974-),女,河南焦作人,理学博士,教授,主要从事退行性疾病新药设计及作用机制研究。E-mail:chunhong_dong@hactcm.edu.cn。
