摘要
[目的]采用网络药理学方法筛选肉桂治疗骨性关节炎(OA)的作用靶点并明确作用机制.[方法]通过检索中药系统药理学成分分析平台获得肉桂的活性化合物并在PubChem数据库中获取所得化合物的SMILES结构,将其导入至SwissTargetPrediction平台中预测活性成分的潜在靶点,再通过GeneCards数据库获得相关化合物靶点,取两者交集得到肉桂作用靶点;检索TTD、Drug Bank、OMIM、GAD、Pharm GKB、DisGe NET数据库获得OA疾病相关靶点,并取与肉桂作用靶点的交集;采用STRING数据库及Cytoscape 3.2.1软件构建靶点相互作用网络图,并利用cytoHubba插件的MCC算法筛选关键靶点;基于DAVID数据库对靶点进行GO富集和KEGG通路富集分析.[结果]共得到肉桂活性化合物18个,肉桂-OA交集靶点40个,经MCC算法筛选得到关键基因10个,即PTGS2、MAPK8、MMP9、ALB、MMP2、MMP1、SERPINE1、TGFB1、PLAU和ESR1.GO富集共33个结果,其中生物过程主要包括胶原蛋白分解代谢过程、炎症反应、DNA转录正调控、氧化应激反应及组织缺氧反应等;分子功能主要包括血红素结合、芳香化酶活性、金属内肽酶活性及过氧化物酶活性等;细胞组成主要包括细胞外间隙、细胞外基质、血液微粒及核被膜内腔等.KEGG富集相关通路共32条,包括破骨细胞分化、花生四烯酸代谢、低氧诱导因子-1、核转录因子-κB、Toll样受体及肿瘤坏死因子等信号通路.[结论]采用网络药理学方法初步预测了肉桂治疗OA的抗炎、影响细胞增殖、分化及凋亡、抗氧化等潜在的作用机制,为肉桂的活性成分研究和实验研究提供了理论依据.
OBJECTIVE To screen the target and mechanism of Cinnamomum cassia Presl in the treatment of osteoarthritis(OA) by network pharmacology method.METHODS The active compounds of Cinnamomum cassia Presl were obtained by searching the pharmacology component analysis platform of traditional Chinese medicine(TCM) system,and their SMILES structure were obtained from PubChem database,then they were imported into the SwissTargetPrediction platform to predict the active ingredient of potential target point,then the targets of related compounds were obtained by GeneCards database,finally the targets of Cinnamomum cassia Presl were gotten by the intersection.TTD,Drug Bank,OMIM,GAD,Pharm GKB,Dis Ge NET database were searched to obtain OA disease related targets,and the intersection with Cinnamomum cassia Presl targets was obtained.STRING database and Cytoscape 3.2.1 software were used to construct the target interaction network diagram,and MCC algorithm of cyto Hubba plug-in was used to screen the key targets.GO enrichment and KEGG pathway enrichment were analyzed based on DAVID database.RESULTS A total of 18 active compounds from Cinnamomum cassia Presl and 40 intersection targets of Cinnamomum cassia Presl-OA were obtained,and 10 key genes were screened by MCC algorithm,namely PTGS2,MAPK8,MMP9,ALB,MMP2,MMP1,SERPINE1,TGFB1,PLAU and ESR1.A total of 33 GO enrichment results were obtained,biological process mainly included the process of collagen protein catabolism,inflammation,positive regulation of DNA transcription,oxidative stress and hypoxia reaction,etc.,molecular function mainly included heme binding,aromatase activity,metalloendopeptidase and peroxidase activity,etc.,cell composition mainly included extracellular space,extracellular matrix,blood particles and nuclear envelope lumen,etc..There were 32 pathways related to KEGG enrichment,including the signal pathway about osteoclast differentiation,arachidonic acid metabolism,hypoxia-inducible factor-1,nuclear factor κB,Toll-like receptors and tumor necrosis factor.CONCLUS
作者
樊燕鑫
权力
沈计荣
FAN Yanxin;QUAN Li;SHEN Jirong(Department of Joint Surgery,Changzhou Hospital of Chinese Medicine,Changzhou 213004,Jiangsu,China;Department of Laboratory,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China;Department of Orthopedics,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,Jiangsu,China)
出处
《延边大学医学学报》
CAS
2023年第2期95-102,共8页
Journal of Medical Science Yanbian University
基金
国家自然科学基金委面上项目基金(批准号:82274552)。
关键词
肉桂
骨性关节炎
网络药理学
Cinnamomum cassia Presl
osteoarthritis
network pharmacology
