摘要
目的:基于网络药理学和分子对接技术预测龟甲治疗骨关节炎(OA)潜在靶点及作用机制。方法:通过BATMAN-TCM、TCMID数据库及文献检索并筛选龟甲活性成分,利用SwissTargetPrediction数据库预测活性成分靶点。运用TTD、PharmGkb、OMIM、DrugBank数据库预测合并筛选OA相关靶点,并取两者交集得到龟甲治疗OA的潜在作用靶点。借助String数据库进行潜在作用靶点的蛋白互作网络构建,运用Cytoscape 3.8.2软件构建可视化网络,CytoNCA插件筛选核心靶点。最后利用iGEMDOCK软件对核心靶点与其相对应成分进行分子对接验证。结果:筛选得到龟甲活性成分27个,对应314个靶点,将其与180个OA相关靶点取交集得到41个潜在作用靶点。其中潜在有效成分主要包括十四酸甾醇酯、(E)-11-二十碳烯酸、十五烷酸等,核心靶点为PTGS2、TNF、MAPK3、PPARG、NR3C1、RXRA,分子对接结果显示其与对应成分之间的结合作用较强。基因本体论(GO)富集得到72条生物过程(P<0.05),主要涉及RNA聚合酶Ⅱ启动子的转录起始、氧化还原过程、脂质代谢过程、细胞内受体信号通路、花生四烯酸代谢过程、类固醇代谢过程等,京都基因与基因组百科全书(KEGG)富集得到33条通路(P<0.05),主要涉及花生四烯酸代谢、过氧化物酶体增殖物激活受体(PPAR)、神经活性配体-受体相互作用、类固醇激素生物合成及癌症途径信号通路等。结论:龟甲可能通过调控炎症、软骨代谢、软骨细胞凋亡发挥预防和治疗OA的作用,需要进一步实验验证。
Objective:To analyze the mechanism of Tortoise Shell in the treatment of osteoarthritis(OA) based on network pharmacology and molecular docking technology.Methods:The Tortoise Shell active compounds were obtained from the database of BATMAN-TCM,TCMID,and literature.Swisstargetprediction was used The database predicts active ingredient targets.Using TTD,PharmGkb,OMIM,DrugBank database predicts and screens OA related targets,and takes the intersection of the two to obtain the potential target of Tortoise Shell in the treatment of OA.The protein-protein interaction network of potential targets was constructed with the help of String database,the visual network was constructed with Cytoscape 3.8.2 software,and the core targets were screened by CytoNCA plug-in.Finally,the core target and its corresponding components were verified by iGEMDOCK software.Results:27 active components of tortoise shell were screened,corresponding to 314 targets.41 potential targets were obtained by intersection with 180OA related targets.The potential active components mainly include tetradecanoic acid sterol ester,(E)-11 eicosenoic acid,pentadecanoic acid,etc.the core targets are PTGS2、TNF、MAPK3、PPARG、NR3C1、RXRA.The molecular docking results show that it has strong binding effect with the corresponding components.Gene Ontology(GO)enriched 72 biological processes(P<0.05),mainly involving transcription initiation,redox process,lipid metabolism process,intracellular receptor signal pathway,arachidonic acid metabolism process,steroid metabolism process,etc.of RNA polymerase Ⅱ promoter.Kyoto Encyclopedia of genes and genomes(KEGG)enriched 33 pathways(P<0.05),It mainly involves arachidonic acid metabolism,peroxisome proliferator activated receptor(PPAR),neuroactive ligand receptor interaction,steroid hormone biosynthesis and cancer pathway signal pathway.Conclusion:Tortoise shell may play a role in the prevention and treatment of OA by regulating inflammation,cartilage metabolism and chondrocyte apoptosis,which needs further experimental verification.
作者
朱香梅
李晴
石雨荷
朱珏
童巧珍
刘湘丹
王智
Zhu Xiangmei;Li Qing;Shi Yuhe;Zhu Jue;TongQiaozhen;Liu Xiangdan;Wang Zhi(College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,China;Key Laboratory of Germplasm Resources and Standardized Planting of Bulk Authentic Medicinal Materials from Hunan,Changsha 410208,China;Key Laboratory of Modern Research of TCM,Education Department of Hunan Province,Changsha 410208,China)
出处
《亚太传统医药》
2022年第7期132-139,共8页
Asia-Pacific Traditional Medicine
基金
湖南中医药大学“东健”研究生创新项目(2020DJ05,2021dj01)
湖南省自然科学基金(2020JJ4466)
财政部和农业农村部:国家现代农业产业技术体系资助项目(CARS-21)。
关键词
龟甲
骨关节炎
网络药理学
分子对接
Tortoise Shell
Osteoarthritis
Network Pharmacology
Molecular Docking
