基于网络药理学和生信分析探讨紫苏醛抗慢性粒细胞白血病的潜在作用机制

Research on Potential Mechanism of Perillaldehyde Against Chronic Myelocytic Leukemia Based on Network Pharmacology and Bioinformatics Analysis

目的基于网络药理学、分子对接及生物信息学分析探究紫苏醛(PAE)抗慢性粒细胞白血病(CML)的潜在作用机制。方法从HERB、BATMAN、TCMSP和SuperPred数据库获取PAE靶点,利用Genecards、DisGeNET、DrugBank和OMIM数据库预测CML的疾病靶点。筛选潜在药物靶点和疾病靶点的交集基因,再进行基于GO及KEGG的富集分析。将富集结果导入STRING数据库,构建蛋白互相作用(PPI)网络图。运用分子对接及生物信息学分析筛选并验证其评分最高的靶点。最后通过酶联免疫吸附测定(ELISA)和蛋白质免疫印迹(Western blot)检测进一步验证了PAE与CXCL8(IL-8)的相互作用关系。结果共得到了53个药物靶点、2415个疾病靶点,其中包括CXCL8在内的交集靶点共18个。分子对接结果证明紫苏醛与核心靶点CXCL8结合潜能较好。生信分析结果显示CXCL8在正常组和患者组之间有显著表达差异。ELISA和Western blot结果一致表明PAE能显著降低CXCL8在慢性粒细胞白血病K562细胞中的表达,并呈现出浓度依赖性。结论CXCL8可能是PAE抗CML的潜在靶点。

Objective To explore the potential mechanism of perillaldehyde(PAE)against chronic myelocytic leukemia(CML)based on network pharmacology,molecular docking and bioinformatics.Methods Action targets of PAE were obtained from HERB,BATMAN,TCMSP and SuperPred databases,and the disease targets of CML were predicted using Genecards,DisGeNET,DrugBank and OMIM databases.The intersecting genes of potential drug targets and disease targets were screened,and then the enrichment analysis based on GO and KEGG was performed.The enrichment results were imported into STRING database to construct a protein interaction(PPI)network map.Then the molecular docking and bioinformatics analysis were used to screen and verify the targets of highest score.Finally,the interaction between PAE and CXCL8(IL-8)was further verified by enzyme-linked immunosorbent assay(ELISA)and Western blot.Results 53 drug targets and 2415 disease targets were obtained,and 18 intersecting targets including CXCL8 were obtained.Molecular docking results demonstrated that PAE had good binding potential with CXCL8.Bioinformatics analysis showed that CXCL8 was significantly differentially expressed between the normal and the patient groups.The ELISA results and Western blot results consistently showed that PAE significantly reduced CXCL8expression in chronic myelocytic leukemia K562 cells in a concentration-dependent manner.Conclusion CXCL8could be a potential target of PAE against CML.