基于网络药理学分析桃红四物汤治疗股骨头坏死的机制

Analysis in mechanism of Taohong Siwu Decoction in the treatment of femoral head necrosis based on network pharmacology

  • 摘要:
      目的  利用网络药理学方法探索桃红四物汤治疗股骨头坏死的作用机制。
      方法  通过中药系统药理学数据库与分析平台(TCMSP)、GeneCards、OMIM、Drugbank数据库获取桃红四物汤治疗股骨头坏死活性成分与靶点,构建活性成分-靶点互作网络,绘制蛋白互作(PPI)网络并进行分子对接,最后行GO富集和KEGG通路富集分析。
      结果  从桃红四物汤中筛选出活性成分69个,作用于股骨头坏死的主要活性成分为槲皮素、山奈酚、木犀草素; 关键靶点为血管内皮生长因子(VEGF)、白细胞介素-6(IL-6)及成骨细胞特异性转录因子2(Runx2)。分子对接服务器分析发现,桃红四物汤的活性成分与关键靶点能够紧密结合。GO富集分析显示,分子功能主要包括转录因子结合、类固醇激素受体活性、蛋白激酶结合等方面。生物过程主要涉及到细胞因子介导的信号通路、对类固醇激素的反应及细胞凋亡信号通路等生物学过程,细胞组成主要包括核转录因子复合体、蛋白激酶复合体、蛋白质-DNA复合物等。KEGG富集分析获取相关信号通路为VEGF、Janus激酶/信号转导与转录激活子(JAK/STAT)及核转录因子-kappa B(NF-κB)信号通路。
      结论  桃红四物汤治疗股骨头坏死的作用机制在于应用槲皮素、山奈酚、木犀草素等活性成分,以VEGF、IL-6及Runx2为靶点,通过VEGF、JAK/STAT及NF-κB信号通路参与治疗股骨头坏死。

     

    Abstract:
      Objective  To explore the mechanism of Taohong Siwu Decoction in the treatment of femoral head necrosis by means of network pharmacology method.
      Methods  Through Traditional Chinese Medicine Systems Pharmacology (TCMSP), GeneCards, OMIM and Drugbank databases, the active components and targets of Taohong Siwu Decoction in the treatment of osteonecrosis of femoral head were obtained, and then the active component-target interaction network, protein-protein Interaction(PPI)network and molecular docking were constructed. Finally, GO enrichment and KEGG pathway enrichment analysis were performed.
      Results  Sixty-nine active ingredients were screened from Taohong Siwu Decoction. The main active ingredients for femoral head necrosis were quercetin, kaempferol, and luteolin; the key targets were vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and runt-related transcription factor 2 (Runx2). Through molecular docking server analysis, it was found that the active components of Taohong Siwu Decoction could bind closely to the key targets. GO enrichment analysis showed that the molecular functions mainly included transcription factor binding, steroid hormone receptor activity, protein kinase binding and so on. Biological processes mainly involved cytokine mediated signaling pathways, response to steroid hormones, apoptosis signaling pathways and other biological processes. Cell components mainly included nuclear transcription factor complex, protein kinase complex, protein-DNA complex and so on. KEGG enrichment analysis revealed that VEGF, Janus kinase/signal transduction and transcriptional activator (JAK/STAT) as well as nuclear transcription factor-kappa B (NF-κB) signaling pathways were involved.
      Conclusion  Taking VEGF, IL-6 and Runx2 as targets, the action mechanism of active ingredients of Taohong Siwu Decoction including quercetin, kaempferol, luteolin and so is to participate in VEGF, JAK/STAT and NF-κB signaling pathways in treatment of femoral head necrosis.

     

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