采用网络药理学和分子对接技术探讨“补肾解毒散结方”治疗结直肠癌的潜在分子机制

Exploration on the Potential Molecular Mechanism of Bushen Jiedu Sanjie Recipe for the Treatment of Colorectal Cancer with Network Pharmacology and Molecular Docking Techniques

目的 采用网络药理学与分子对接技术,探讨“补肾解毒散结方”治疗结直肠癌(Colorectal cancer,CRC)的潜在分 子作用机制。方法 采用网络药理学与分子对接技术,利用 TCMSP、PubChem、Swiss Target Prediction数据库检索“补肾解 毒散结方”主要组方生地黄、女贞子、肉苁蓉和山慈菇的活性成分及潜在靶点,通过 Genecards、OMIM数据库检索结直肠 癌的治疗靶点。利用 Venny2.1.0软件构建药物与疾病交集靶点,STRING数据库建立靶点蛋白相互作用关系,Cytoscape3.6.1 软件构建“药物-活性成分-靶点”网络。基于 Bioconductor数据库运用 R语言分析软件对核心靶点进行 GO功能分析和 KEGG 通路富集分析。通过 AutoDockTools-1.5.6等软件预测核心靶点与核心成分的分子对接。结果 “补肾解毒散结方”共有 20种 活性成分和 37个“药物-疾病”交集靶点。GO功能分析得到 957条生物学过程、20个细胞组分、76个分子功能,KEGG富 集分析得到涉 HIF-1、PI3K-Akt、病毒感染、p53、细胞凋亡等 102条信号通路,同时,分子对接结果初步验证了核心靶点 AR、BCL2、CASP3、CASP9、PPARG、PRSS1等与山奈酚、木犀草素、槲皮素等活性成分间具有较好的结合活性。结论 “补肾解毒散结方”可能通过活性成分山奈酚、木犀草素、槲皮素与 AR、BCL2、CASP3、CASP9、PPARG、PRSS1等靶蛋白 结合发挥防治结直肠癌的作用,为结直肠癌的治疗研究和临床应用提供了理论依据。

Objective To investigate the potential molecular mechanism of “Bushen Jiedu Sanjie prescription” in the treatment of Colorectal cancer(CRC) by using network pharmacology and molecular docking technology. Methods TCMSP,PubChem,and Swiss Target Prediction databases were used to screen the active ingredients and potential targets of Radix Rehmanniae Preparata, Fructus Ligustri Lucidi, Herba Cistanches, and Pseudobulbus Cremastrae seu Pleiones in Bushen Jiedu Sanjie Recipe. Genecards and OMIM database were used 21 for the retrieval of colorectal cancer related targets. Venny2.1.0 software was used for constructing the intersection target of drugs and diseases. And then the protein interaction targets were obtained by using the STRING database, and Cytoscape3.6.1 software was used to construct the drug-active components-targets network. On the basis of Bioconductor database, R language analysis software was used for GO function analysis and KEGG pathway enrichment analysis. Autodocktools-1.5.6 was used for molecular docking to predict the binding energy of core targets and core components. Results The results showed that a total of 20 active ingredients of Bushen Jiedu Sanjie Recipe and 37 intersection targets of medicine-disease were screened out. The results of GO function analysis showed that 957 biological processes, 20 cell components, and 76 kinds of molecular function were obtained. KEGG enrichment analysis presented 102 signaling pathways associated with HIF-1,PI3K-Akt,viral infection, p53, and cell apoptosis. The molecular docking preliminary demonstrated that the core targets AR, BCL2, CASP3, CASP9, PPARG and PRSS1 were related to kaempferol, luteolin, quercetin and other active ingredients with good binding activity. Conclusion “Bushen Jiedu Sanjie Recipe” may play a role in the prevention and treatment of colorectal cancer through the combination of active ingredients kaempferol,luteolin, quercetin with AR, BCL2, CASP3, CASP9, PPARG, PRSS1 and other target proteins, which provides a theoretical basis for the therapeutic research and clinical application of colorectal cancer.