基于网络药理学和分子对接探讨沉香药效的作用机制

Study on the Mechanism of Action of Agarwood Based on Network Pharmacology and Molecular Docking

目的:运用网络药理学和分子对接探讨沉香药效的作用机制。方法:运用TCMSP数据库搜索沉香的化学成分,利用OB和DL作为筛选指标得到有效活性成分,STRING 11.0数据库得到靶点和与其相对应的疾病,通过Cytoscape3.7.2软件建立化合物-靶点网络、蛋白相互作用网络、靶点-疾病网络,David v6.7数据库进行GO和KEGG富集分析,探究其作用机制。结果:筛选出9个化合物,265个靶点,疾病1073种,168个蛋白,39个基因功能条目,84条信号通路。选用较好的活性组分槲皮素、谷甾醇、6,7-二甲氧基-2-(2-苯乙基)色酮、6,7-二甲氧基-2-(2-(4-甲氧基苯基)乙基)色原酮与核心靶点PTGS1、HSP90AA1、AR、PTGS2、AKT1、IL6、TP53、VEGFA进行分子对接验证。6,7-二甲氧基-2-(2-苯乙基)色酮与PTGS1亲和力较好。结论:沉香以多成分-多靶点-多通路的方式发挥治疗的效果,分子对接验证初测结果,为进一步研究沉香药效的分子作用机制提供理论基础。

Objective:To explore the mechanism of of action of agarwood by network pharmacology and molecular docking.Method:TCMSP database was useed to search the chemical components of agarwood,OB and DL were used as the screening indexes to obtain the active components,The target and corresponding diseases were obtained from STRING 11.0 database.Compound target network,protein interaction network and target disease network were established by using the software of Cytoscape 3.7.2.The enrichment of GO and KEGG was analyzed in v6.7 database to explore its mechanism of action.Results:9 compounds,265 targets and 1073 diseases were screened out.There were 168 proteins,39 gene function entries,84 signal pathways.Quercetin,sitosterol,6,7-dimethoxy-2-(2-phenethyl)chromone,6,7-dimethoxy-2-(2-(4-methoxyphenyl)ethyl)chromone and the core targets PTGS1,HSP90AA1,AR,PTGS2,AKT1,IL6,TP53,VEGFA were selected for molecular docking verification.6,7-Dimethoxy-2-(2-phenylethyl)chromone has good affinity with PTGS1.Conclusion:Agarwood has the therapeutic effect in the way of multi-component,multi-target,and multi channel.The preliminary test results of molecular docking are verified,which provides a theoretical basis for further research on the molecular mechanism of agarwood efficacy.