[关键词]
[摘要]
目的 利用网络药理学方法建立厚朴“发汗”前后的差异成分-靶点网络,并探究厚朴“发汗”前后药理作用差异的分子机制,进而揭示其发汗的科学内涵。方法 通过查阅文献并筛选厚朴“发汗”前后的差异成分。利用Swiss Target Prediction预测差异成分的潜在靶点。利用STRING数据库筛选出最高置信度(得分0.900)的靶点并通过Cytoscape 3.6.0软件构建蛋白-蛋白互作网络。最后利用R Project中的clusterProfiler包对蛋白-蛋白互作网络进行GO注释和KEGG通路富集分析。结果 通过查阅文献共筛选出9种差异成分(阿西米诺宾、β-桉叶醇、和厚朴酚、厚朴三酚B、木兰花碱、厚朴酚、紫丁香苷、瑞枯灵和magnoloside A)并预测得到137个靶点(除重后共86个)。通过对蛋白-蛋白互作网络GO注释及通路富集分析,共得到550个GO注释和30条KEGG通路。结论 数据分析结果表明,“发汗”后厚朴药理作用的改变是化学成分相互作用的最终结果。其中,厚朴主要是通过5-羟色胺能突触、花生四烯酸代谢和钙信号通路发挥镇痛和抗胃溃疡作用。厚朴酚、和厚朴酚及β-桉叶醇等化学成分含量的改变是厚朴“发汗”前后疗效差异的主要原因。
[Key word]
[Abstract]
Objective Sweating is one of the important processing methods of traditional Chinese medicine. Some ingredient content of Magnoliae Officinalis Cortex (MOC) is changed after sweating which may cause the difference of efficacy. However, the molecular mechanism of how the changes of ingredient content of MOC affect the efficacy is not clear exactly. Based on the network pharmacology, the relationship between the changes of the ingredient content of MOC and the efficacy after sweating was studied. Methods The major difference of chemical ingredients before and after sweating were screened out based on the literatures. Swiss Target Prediction was used to predict the potential targets of these components. The high confidence (score 0.900) genes/targets selected out by STRING database were used to construct protein-protein interactions network by using cytoscape 3.6.0. The clusterProfiler package in R was used to analyze gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway. Results Nine different components (asimilobine, β-eudesmol, honokiol, magnatriol B, magnoflorine, magnolol, magnoloside A, reticuline, and syringin) were screened out. A total of 137 genes/targets were obtained (86 after deduplication). After GO annotation and KEGG enrichment analysis of the network, 550 GO-terms and 30 KEGG pathways were obtained. Conclusion Through analysis, the change in the pharmacological effects of MOC after sweating is the result of the interaction between the components. The analgesic and anti-gastric ulcer effects of MOC may be mainly produced through the serotonergic synapse, arachidonic acid metabolism and calcium signaling pathway. And the changes in the content of chemical components such as magnolol, honokiol and β-eudesmol are the main reasons for the difference in the efficacy of MOC before and after sweating.
[中图分类号]
[基金项目]
国家自然科学基金青年基金项目(81603300);四川省教育厅基金项目(16ZA0107);成都中医药大学杏林学者计划(QNXZ2018006)