基于网络药理学和蛋白模块分析淫羊藿治疗骨关节炎的作用与机制

文题释义：网络药理学：是基于系统生物学的理论，对生物系统的网络分析、选取特定信号节点进行多靶点药物分子设计的新学科。网络药理学强调对信号通路的多途径调节，提高药物的治疗效果，降低毒副作用，从而提高新药临床试验的成功率，节省药物的研发费用。 淫羊藿：为小檗科多年生草本植物，其性温，味辛，归肝经、肾经，传统中医药理论认为淫羊藿具有补肾壮阳、强筋健骨、祛除风湿痹痛等功效，临床上广泛将其应用于骨关节炎疾病的治疗。淫羊藿参与调控骨关节炎的信号通路主要有白细胞介素受体通路、肿瘤坏死因子信号通路、Toll样受体信号通路、T细胞受体信号通路、NF-κB信号通路、破骨细胞分化通路(RANK/RANKL/OPG)。 背景：现代中药药理学研究表明淫羊藿苷在骨关节炎方面有着非常积极的作用。由于淫羊藿所含化学成分较为复杂，且在分子水平上治疗骨关节炎的机制尚不明确，因此利用网络药理学从分子水平来解释淫羊藿治疗骨关节炎的潜在化学成分及作用机制，可为后期药物研发及疾病治疗提供一定理论依据。 目的：采用网络药理学方法探讨淫羊藿治疗骨关节炎的分子机制。 方法：通过TCMSP数据库筛选淫羊藿的药效成分，通过TCMSP、Swiss Target Prediction和STITCH数据库预测淫羊藿药效成分的调控靶点，通过OMIM、GeneCards和TTD数据库预测治疗骨关节炎的靶点，将淫羊藿药效靶点与骨关节炎治疗靶点取交集，得到淫羊藿治疗骨关节炎的靶点，并构建“药物-成分-靶点-疾病”网络。通过STRING数据库分析蛋白互作关系，运用DAVID数据库分析蛋白模块的相关信号通路和功能。 结果与结论：①筛选得到23个淫羊藿药效成分，共预测得到230个淫羊藿药效靶点和1 221个骨关节炎的治疗靶点，取交集后得到95个淫羊藿治疗骨关节炎的靶点，蛋白互作分析提示JUN、AKT1、RELA、MAPK1、IL6、CXCL8、MAPK8、MAPK14、FOS、IL1B为蛋白互作网络中的核心靶点；②关键蛋白模块主要涉及白细胞介素受体通路、肿瘤坏死因子信号通路、Toll样受体信号通路、T细胞受体信号通路、NF-κB信号通路和破骨细胞分化通路，可能通过调控细胞增殖与凋亡、免疫细胞及免疫反应、炎症因子及炎症反应、脂多糖的细胞反应等多种生物过程发挥治疗骨关节炎的作用。 ORCID: 0000-0002-2572-0229(章晓云) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Mechanisms of Epimedium in the treatment of osteoarthritis based on network pharmacology and protein module

BACKGROUND:Pharmacological studies in modern Chinese medicine have shown that icariin has a very positive effect on osteoarthritis.Because of the complex chemical composition of Epimedium and its unclear mechanism underlying the treatment of osteoarthritis at the molecular level,network pharmacology is introduced to explain the potential chemical components and molecular mechanism of Epimedium in the treatment of osteoarthritis.This can provide a theoretical basis for future drug development and disease treatment.OBJECTIVE:To explore the molecular mechanism of Epimedium in the treatment of osteoarthritis based on network pharmacology.METHODS:TCMSP database was used to screen the active ingredients of Epimedium.TCMSP,Swiss Target Prediction and STITCH database were used to predict the regulatory targets of the active ingredients of Epimedium.OMIM,GeneCards and TTD database were used to predict the therapeutic targets of osteoporosis.The therapeutic target of Epimedium for osteoporosis was obtained by intersecting the therapeutic target of Epimedium and osteoarthritis.A drug-component-target-disease network was then constructed.The protein interaction was analyzed by STRING database,and the related signaling pathways and functions of protein modules were analyzed by DAVID database.RESULTS AND CONCLUSION:Twenty-three pharmacodynamic components of Epimedium were screened and 230 pharmacodynamic targets of Epimedium and 1221 therapeutic targets of osteoarthritis were predicted.After crossing,95 therapeutic targets of Epimedium for osteoporosis were obtained.Protein interaction analysis indicated that JUN,AKT1,RELA,MAPK1,IL6,CXCL8,MAPK8,MAPK14,FOS and IL1B were the core targets of protein interaction network.Key protein modules were mainly involved in interleukin receptor pathway,tumor necrosis factor signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,nuclear factor-kappa B signaling pathway and osteoclast differentiation pathway.They might play a role in the treatment of osteoarthritis by regulating many biological processes such as cell proliferation and apoptosis,immune cells and immune response,inflammatory factors and inflammatory response,and lipopolysaccharide cell response.