基于化学生物信息学方法探讨黄芪通过调节能量代谢发挥“补气”功效的物质基础和分子机制

Exploration on Material Basis and Molecular Mechanism of Astragali Radix Exerting the Effect of “Invigorating Qi” Through Regulating Energy Metabolism Based on Chemo-bio Informatics Methods

关键词:  黄芪  补气  能量代谢  化学生物信息学

Key words:  Astragali Radix  invigorating Qi  energy metabolism  chemo-bio informatics

摘要:

目的 阐释黄芪发挥“补气”功效调节能量代谢的物质基础和生物学机制。方法 TCMSP数据库及文献检索收集黄芪潜在活性成分，SEA数据库进行基于结构相似性的靶点预测，GeneCards、OMIM、TTD数据库获取能量代谢靶点。Cytoscape软件构建黄芪调节能量代谢靶点蛋白-蛋白相互作用网络图，并进行GO和KEGG富集分析。黄芪全成分与关键靶点进行分子对接和层次聚类分析评估靶点-成分亲和力，采用CCK-8法、流式细胞术、ATP试剂盒检测黄芪代表性化合物对H9C2心肌细胞、GES-1胃上皮细胞能量代谢的影响，并进行结合模式分析。结果 网络药理学结果显示，黄芪调节能量代谢潜在作用靶点有126个；GO和KEGG富集分析表明，黄芪调节能量代谢可能与氧化还原过程、蛋白及酶合成的基因表达有关。其中，SIRT1及PPARγ是参与能量代谢调节的关键靶点。分子对接及层次聚类显示黄芪成分对SIRT1及PPARγ具有较好的靶向性，结合分子对接打分值筛选出3个代表性化合物进行体外实验验证；槲皮素、山奈酚能够促进H9C2心肌细胞、GES-1胃上皮细胞能量代谢。结合模式分析表明，槲皮素、山奈酚与SIRT1、PPARγ之间具有较好的结合能力。结论 本研究通过中医药化学生物信息学方法初步阐释了黄芪调节能量代谢的物质基础和生物机制，为黄芪通过“补气”发挥行滞通痹功效的中医内涵提供了科学依据。

Abstract:

OBJECTIVE To explain the material basis and biological mechanism of Astragali Radix’s “invigorating Qi” effect to regulate energy metabolism. METHODS The TCMSP database and literature search collected potential active components of Astragali Radix, the SEA database performed target prediction based on structural similarity, and the GeneCards, OMIM, and TTD databases obtained energy metabolism targets. Cytoscape software was used to construct protein-protein interaction network maps of Astragali Radix regulated energy metabolism targets, and GO and KEGG enrichment analyses were performed. Molecular docking and hierarchical cluster analysis were performed to evaluate the target-component affinity between the whole constituents of Astragali Radix and key targets, and the effects of representative compounds of Astragali Radix on the energy metabolism of H9C2 cardiomyocytes and GES-1 gastric epithelial cells were detected, and the binding mode analysis was conducted. RESULTS Network pharmacology results showed that there were 126 potential targets of Astragali Radix regulating energy metabolism. GO and KEGG enrichment analysis showed that Astragali Radix regulating energy metabolism might be related to gene expression of oxidation-reduction process, protein and enzyme synthesis. Among them, SIRT1 and PPARγ were key targets involved in the regulation of energy metabolism. Molecular docking and hierarchical clustering showed that Astragali Radix components had superior targeting to SIRT1 and PPARγ, and three representative compounds were selected for in vitro experimental verification in combination with molecular docking scores. Quercetin and kaempferol could promote energy metabolism in H9C2 cardiomyocytes and GES-1 gastric epithelial cells. The binding mode analysis showed that quercetin and kaempferol had preferable binding ability to SIRT1 and PPARγ. CONCLUSION In this study, the material basis and biological mechanism of Astragali Radix regulating energy metabolism are preliminarily explained by traditional Chinese medicine chemo-bio informatics methods, which provide a scientific basis for the connotation of Astragali Radix exerting the effect of stagnation and arthralgia through “invigorating Qi” in traditional Chinese medicine.