基于GC-MS和网络药理学分析白木香茶抗糖尿病机制

    Analysis on the Anti-Diabetic Mechanism of Aquilaria Sinensis Tea Based on GC-MS and Network Pharmacology

    • 摘要: 探究白木香茶活性成分及治疗糖尿病的作用机制。气相色谱-质谱联用法(GC-MS)分析白木香茶活性成分,利用Swiss Target Prediction数据库收集活性成分对应的靶点,以及GeneCards和OMIM数据库获取糖尿病相关的靶点,将成分靶点与疾病靶点经Venny分析筛选出潜在靶点。通过Cytoscape3.7.1软件构建成分靶点-疾病靶点网络、STRING数据库蛋白质相互作用网络、DAVID数据库对潜在靶点进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,利用RCSB PDB数据库和AutoDockTools 1.5.6软件对核心靶点进行分子对接验证。GC-MS法鉴定得到植醇、木栓酮和β-香树酮等23个活性成分;通过数据库收集到372个活性成分靶点与3168个糖尿病相关靶点,筛选出183个白木香茶治疗糖尿病的潜在靶点。这些潜在靶点主要富集于以下功能与通路,生物过程方面有胰岛素受损信号、胰岛素样生长因子受体信号、ERK1和ERK2级联的正调控等;细胞组成方面有质膜、受体复合物、细胞膜等;分子功能方面有跨膜受体、胶原受体的酪氨酸激酶活性、血小板衍生生长因子a受体活性等。KEGG通路分析显示,潜在靶点主要涉及癌症信号通路、胰岛素抵抗通路和内分泌抵抗通路等。分子对接结果表明,核心成分与关键靶蛋白均能稳定结合。综上,白木香茶活性成分通过多成分-多靶点-多通路的方式发挥治疗糖尿病作用,推测白木香茶中α-生育酚、β-香树酮、植醇等活性成分可能通过AKT1、IL-1β、SRC等关键靶蛋白,调节癌症、胰岛素抵抗通路和内分泌抵抗通路等通路,达到治疗糖尿病的作用,为开发糖尿病治疗的天然药物提供了理论依据。

       

      Abstract: This study aimed to explore the active components of Aquilaria sinensis tea and their therapeutic mechanism in diabetes treatment. The active components of Aquilaria sinensis tea were analyzed by gas chromatography-mass spectrometry (GC-MS). The Swiss Target Prediction database was used to collect the targets corresponding to these active components, while the diabetes-related targets were collected from the GeneCards and OMIM databases. Then, the component targets and disease targets were screened for the potential therapeutic targets by using Venny analysis. The Cytoscape 3.7.1 software was used to construct the component target-disease target network, and the STRING database was applied to build a protein-protein interaction (PPI) network. The DAVID database was used for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the potential targets. The molecular docking validation of the core targets was performed by using the RCSB PDB database and AutoDockTools 1.5.6 software. Twenty-three active components such as phytol, friedelin and β-amyrin were identified by using the GC-MS method. Through the database, 372 active component targets and 3,168 diabetes-related targets were collected, from which 183 potential targets for A. sinensis tea in the treatment of diabetes were screened out. These potential targets were mainly enriched in the following functions and pathways, such as the insulin impairment signaling, insulin-like growth factor receptor signaling, and positive regulation of the ERK1 and ERK2 cascades in the biological processes. The cellular components included the plasma membrane, receptor complexes, and cell membrane, etc.; in terms of molecular function, there were kinase activity of transmembrane receptors and collagen receptors, and platelet-derived growth factor alpha receptor activity. The KEGG pathway analysis revealed that the potential targets were mainly involved in the pathways related to cancer, insulin resistance, and endocrine resistance. The results of molecular docking showed that the core components could bind to the key target proteins stably. In conclusion, the active components of A. sinensis tea played a role in the treatment of diabetes through a multi-component, multi-target, and multi-pathway approach. It was speculated that the active components such as α-tocopherol, β-amyrin and phytol in A. sinensis tea may modulate the key target proteins including AKT1, IL-1β, and SRC, thereby regulating the pathways related to cancer, insulin resistance, and endocrine resistance, so as to achieve the therapeutic effects against diabetes, which provided a theoretical basis for the development of natural medicines for diabetes treatment.

       

    /

    返回文章
    返回