基于网络药理学和分子对接预测身痛逐瘀汤治疗神经病理性疼痛的作用机制研究

Network pharmacology prediction and molecular docking-based strategy to explore the mechanism of Shentong Zhuyu Decoction treat neuropathic pain

摘要:

目的：通过网络药理学和分子对接研究身痛逐瘀汤治疗神经病理性疼痛的作用机制。方法：通过TCMSP和HERB数据库获取身痛逐瘀汤活性成分及对应靶点,在GeneCards,OMIM数据库搜索神经病理性疼痛相关靶点,对药物靶点和疾病靶点取交集,获取交集靶 点。通过Cytoscape3.8.0构建“中药-活性成分-靶点”网络；借助STRING 11.0数据库构建蛋白互作网络,同时借助Cytoscape3.8.0软件中Analyze Network插件计算网络中节点的拓扑参数,筛选出网络中起重要作用的核心靶点。将交集靶点投射到GO和KEGG富集分析。最后,借助 AutoDock Vina 1.1.2平台进行分子对接,预测身痛逐瘀汤主要活性成分与核心靶点的结合度。结果：通过筛选得到身痛逐瘀汤活性成分199个, 靶点478个；神经病理性疼痛相关靶点1902个；药物与疾病的交集靶点122个。其中STAT3、IL6、MAPK1、MAPK3、TNF等靶点在身痛逐瘀汤干预神经病理性疼痛的生物网络中起到重要作用,主要涉及 MAPK、cAMP、IL-17等信号通路。分子对接结果显示身痛逐瘀汤活性化合物与MAPK3、FOS、IFNG等关键靶点具有较高结合能力。结论：身痛逐瘀汤可通过多靶点、多途径对神经病理性疼痛产生镇痛作用, 为其治疗神经病理性疼痛的作用机制提供新思路。

Abstract:

Objective: To explore the mechanism of Shentong zhuyu decoction(STZYT)in the treatment of neuropathic pain by network pharmacology and molecular docking. Methods:The principal components and corresponding protein targets of STZYT were searched on TCMSP and HERB, The targets related to neuropathic pain were searched in GeneCards and OMIM databases, and the intersection of drug targets and disease targets was obtained. The "TCM-Active ingredients-Target"network was constructed by Cytoscape3.8.0.The coincidence target was imported into STRING database to construct a PPI network. We further performed GO and KEGG enrichment analysis on the targets. Finally, molecular docking study was approved for the core target and the active compound. Results: 199 active ingredients and 478 targets of STZYT were obtained. There were 1902 neuropathic pain related targets. There were 122 intersection targets of drugs and diseases. Among them, STAT3, IL6, MAPK1, MAPK3, TNF and other targets play an important role in the biological network of STZYT to interfere with neuropathic pain, mainly involving MAPK, cAMP, IL-17 and other signaling pathways. Molecular docking results showed that the active compounds of STZYT had high binding ability with MAPK3, FOS, IFNG and other key targets. Conclusion： STZYT can produce analgesic effect on neuropathic pain through multi-target and multi-pathway, and provide a new idea for the mechanism of action of STZYT in the treatment of neuropathic pain.