基于网络药理学和分子对接技术探讨桃红四物汤治疗原发性痛经的有效成分及作用机制

Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology

通过网络药理学结合分子对接技术研究桃红四物汤治疗原发性痛经的有效成分及作用机制。首先利用TCMSP平台检索桃红四物汤中6味中药的化学成分和作用靶点,并通过DrugBank,OMIM,TTD和CTD等数据库筛选出治疗PD的靶标,借助Uniprot数据库对靶点进行基因注释,取药物-疾病交集基因通过Cytoscape 3.7.2构建药物-化合物-靶点网络,再基于STRING构建PPI蛋白互作网络,根据拓扑学参数筛选桃红四物汤治疗PD的核心靶点,通过DAVID进行GO功能富集分析,KOBAS 3.0进行KEGG通路富集分析,最后将网络中度值较高的成分与核心靶点进行分子对接。分析结果显示网络中包含槲皮素、山柰酚、木犀草素、杨梅酮、阿魏酸等36个化合物和PTGS2,PTGS1,PGR,PPARG等99个靶点,GO功能富集分析得到102个GO条目(P<0.01),KEGG通路富集得到228条信号通路(P<0.05),主要涉及炎症因子、免疫调节、激素水平调节、中枢镇痛以及平滑肌痉挛等信号通路。分子对接结果显示主要活性成分与靶点均能自发结合。该研究初步揭示了桃红四物汤通过多成分-多靶点-多通路治疗原发性痛经的作用机制,为桃红四物汤的机制研究提供理论依据。

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.