基于网络药理学探究筋痛灵膏外用治疗肩关节周围炎的作用机制

Mechanism of external application of Jintongling ointment in treatment of periarthritis of shoulder based on network pharmacology

目的通过网络药理学对筋痛灵膏外用治疗肩关节周围炎的主要活性成分及其潜在的作用机制进行研究。方法筋痛灵膏的主要活性成分和靶标于中药系统药理学分析平台(TCMSP)获取,肩关节周围炎的靶标通过五大疾病数据库查找获得。药物-疾病交互靶点在Venny平台上获取,并建立蛋白质相互作用网络来筛选出核心靶点。交集靶点在Metascape平台上进行基因本体论(GO)和京都基因与基因组大百科全书数据库(KEGG)的富集分析。最后对药物主要成分和核心靶点进行分子对接。结果共筛选出53个活性成分,121个重要靶点;其中,核心活性成分为槲皮素、β-谷甾醇、谷甾醇、黄芩素,关键靶点为JUN、ESR1、TP53。GO功能富集分析得出筋痛灵膏作用的生物途径包括对异生素刺激的反应、细菌来源分子的反应、伤口愈合以及氧气水平的反应等。KEGG通路富集分析表明筋痛灵膏治疗肩关节周围炎主要富集在白细胞介素17信号通路、肿瘤坏死因子信号通路、糖尿病并发症中的AGE-RAGE信号通路等。结论筋痛灵膏通过核心成分调控JUN、ESR1、TP53关键靶点,作用于多种生物途径来参与调节免疫反应、减少炎性反应,以达到治疗肩关节周围炎的作用。

Objective To study the potential mechanism of the main active ingredients of Jintongling ointment in the treatment of periarthritis of shoulder by network pharmacology.Methods The main active components and targets of Jintongling ointment were obtained from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),and the targets of periarthritis of shoulder were obtained searching the five disease databases.The drug-disease interaction targets were obtained from the Venny platform,and the protein interaction network was established to screen the core targets.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the Metascape platform.Finally,molecular docking was performed on the drug's main components and core targets.Results Fifty-three active components and 121 important targets were screened out;among them,the core active components were quercetin,β-sitosterol,sitosterol,and baicalein,and the key targets were JUN,ESR1,and TP53.GO functional enrichment analysis showed that the biological pathways of Jintongling ointment included the responses to exogenous stimuli and bacterial source molecules,wound healing,and the response to oxygen level.The KEGG pathway enrichment analysis showed that the treatment of periarthritis of shoulder with Jintongling ointment was mainly enriched in interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,AGE-RAGE signaling pathway in diabetic complications,etc.Conclusion Jintongling ointment regulates JUN,ESR1,and TP53 key targets through core components and acts on a variety of biological pathways to participate in the regulation of immune response and reduce inflammatory response,so as to achieve the effect of treating periarthritis of shoulder.