基于网络药理学探讨消瘤藤治疗子宫肌瘤的作用机制

The Mechanism of Xiaoliuteng(Pileostegia Tomentella)in the Treatment of Fibroid Based on Network Pharmacology

目的:应用网络药理学方法搜索消瘤藤治疗子宫肌瘤的活性成分、靶基因及信号通路,探讨消瘤藤抗子宫肌瘤的作用机制。方法:采用95%乙醇加热回流提取消瘤藤药材,利用HPLC-LTQ/Orbitrap MS技术对消瘤藤提取物进行检测。通过对照品、分子量和质谱裂解规律对消瘤藤化学成分进行鉴定。运用Swiss Target Prediction、GeneCards在线预测消瘤藤化学成分与“散瘀、消肿”相关的潜在靶点,在DAVID 6.8平台进行基因功能富集和KEGG通路富集分析,Cytoscape 3.6.0软件构建“成分-靶点-通路”网络,Autodock软件对核心成分与关键蛋白进行分子对接验证。结果:从消瘤藤中鉴定了14个化学成分,通过网络药理学预测出14种成分与“血瘀”“子宫肌瘤”相关潜在靶点23个,重要通路7条。结论:消瘤藤的活性成分在蛋白多糖、黏附斑激酶、Rap1及Ras通路具有关键作用,可能通过调节胰岛素样生长因子1受体(IGF1R)、表皮生长因子受体(EGFR)等靶点,通过多通路的方式共同作用起到“散瘀、消肿”作用。

Objective:To explore the active ingredients,target genes and signal pathways of Xiaoliuteng(Pileostegia tomentella)in the treatment of fibroid and to explore the anti-fibroid mechanism of Xiaoliuteng(Pileostegia tomentella)according to network pharmacology.Methods:The Xiaoliuteng(Pileostegia tomentella)was extracted by reflux extraction using 95%ethanol as solvent.The chemical constituents were separated and identified by HPLC-LTQ/Orbitrap MS.The chemical components of Xiaoliuteng(Pileostegia tomentella)were identified by reference substance,molecular weight and mass spectrometry fragmentation pattern.The Swiss Target Prediction and GeneCards were used to predict the potential target related to the chemical components of Xiaoliuteng(Pileostegia tomentella)and"dispersing blood stasis and reducing swelling".Gene ontology enrichment analysis and KEGG pathway enrichment analysis were performed on the DAVID6.8 platform,and the"component-target-path"network map was built by Cytoscape 3.6.0.Molecular docking of citrusinol with cytoskeletal protein was carried out by Autodock.Results:Totally 14 major constituents were separated and identified by tandem mass spectrometer,and 23 potential target and 7 important pathways were predicted by network pharmacology among the 14 major constituents.Conclusion:The active ingredient from Xiaoliuteng(Pileostegia tomentella)played key roles in proteoglycans,focal adhesion,Rap1 and Ras signaling pathway.They may work together through multiple pathways by regulating targets such as insulin-like growth factor 1 receptor(IGF1R)and epidermal growth factor receptor(EGFR)to dispell blood stasis and reduce swelling.