基于网络药理学和分子对接探讨藏药唐古特乌头抗炎作用机制  

The anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology and molecular docking

作　　者：柏远 陈晓 李竣[1] 史建勋 黄先菊[1] BAI Yuan;CHEN Xiao;LI Jun;SHI Jian-xun;HUANG Xian-ju(School of Pharmacy,South-central Minzu University,Wuhan 430074,China;Hubei Yaosheng Chinese Medicine Science and Technology Corperation,Zaoyang Hubei 441200,China;Zhejiang Pharmaceutical College,Ningbo Zhejiang 315100,China)

机构地区：[1]中南民族大学药学院,湖北武汉430074 [2]湖北药昇中药科技有限公司,湖北枣阳441200 [3]浙江医药高等专科学校,浙江宁波315100

出　　处：《中国药理学通报》2023年第1期161-169,共9页Chinese Pharmacological Bulletin

基　　金：湖北省支持企业技术创新发展项目(No2021BLB174);国家自然科学基金资助项目(No81374064)。

摘　　要：目的基于网络药理学、分子对接技术及体外细胞实验验证,拟探讨唐古特乌头抗炎作用的潜在分子机制。方法文献调研并使用数据库检索并筛选得到唐古特乌头活性成分靶点和疾病靶点;交集得到共同靶点,构建protein protein interaction(PPI)网络,得出核心靶点,绘制成分-靶点-疾病网络;对共同靶点进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析;将唐古特乌头二萜类生物碱活性成分和部分核心靶点进行分子对接验证。最后基于RAW264.7细胞体外炎症模型,采用MTT法、Griess试剂盒和实时荧光定量RT-PCR等方法验证唐古特乌头醇提物的药效及机制。结果文献搜集得到唐古特乌头17种活性成分,交集得到284个共同靶点;KEGG富集得到PI3K-Akt、Ras、MAPK、HIF-1等108条通路;分子对接结果显示,唐古特乌头活性成分与对接的核心靶点均具有较高的亲和力;体外细胞炎症实验表明,唐古特乌头能够抑制LPS诱导的RAW264.7细胞上清液中NO的释放,减少iNOS的表达。实时荧光定量RT-PCR显示,唐古特乌头可以通过调节PI3K-Akt信号通路发挥抗炎作用。结论唐古特乌头可通过PI3K-Akt等通路发挥抗炎作用,为更好地推进其开发应用提供了科学根据。Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment.Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database.The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network.Then the component-target-disease network diagram was constructed.The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets.AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum.Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR.Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets.Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1.Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked.In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells.Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway.Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.

关 键 词：唐古特乌头 网络药理学 分子对接 抗炎 机制 通路 

分 类 号：R282.71[医药卫生—中药学] R319[医药卫生—中医学] R971.1