基于整合药理学探讨薏苡附子败酱散对胃肠癌“异病同治”作用机制

Exploring the Mechanism of Yiyi Fuzi Baijiang Powder in the Treatment of Gastric and Colorectal Cancers Based on Integrated Pharmacology

目的:通过整合药理学探讨薏苡附子败酱散对胃癌和肠癌“异病同治”的潜在作用机制。方法:运用TCMSP、SwissTargetPrediction、PharmMapper数据平台预测薏苡附子败酱散相关成分及作用靶点,与通过OMIM、DisGeNET、GeneCards数据库收集的胃癌(GC)、结直肠癌(CRC)相关靶点进行交互,将交互靶点借助DAVID数据库平台进行基因本体功能(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,利用Cytoscape软件构建“化合物-靶点-通路”网络;最后通过分子对接预测薏苡附子败酱散活性成分与靶点蛋白的结合能力。结果:从数据库共筛选出薏苡附子败酱散44个有效成分以及968个作用靶点,与GC、CRC进行交集后得到交集靶点463个;利用Network Analyer插件筛选出金合欢素、蒙花苷、脱氧穿心莲内酯等10个核心成分,肿瘤蛋白p53(TP53)等10个核心靶点。GO功能共富集蛋白质磷酸化等1870个条目;KEGG共富集表皮生长因子(EGFR)、血管内皮生长因子(VEGF)等195条通路。分子对接结果进一步证实金合欢素、蒙花苷、脱氧穿心莲内酯等具有良好的构效关系。结论:薏苡附子败酱散可能通过作用于AKT1、TP53、PIK3CA等核心靶点调控p53、EGFR、VEGF、HIF-1等信号通路,发挥对胃癌、肠癌“异病同治”的作用。

Objective:To explore the potential mechanism of Yiyi Fuzi Baijiang Powder(YFBP)in the treatment of gastric and colorectal cancers based on integrated pharmacology.Utilizing an integrated pharmacological approach,the study aims to investigate the potential mechanism of Yiyi Fuzi Baijiang Powder(YFBP)for treating gastric and colorectal cancers.Through the exploration of integrated pharmacology,a deeper understanding can be gained regarding how Yiyi Fuzi Baijiang Powder(YFBP)exerts its therapeutic effects on gastric and colorectal cancers.Methods:The prediction of relevant components and targets of YFBP in the context of gastric cancer(GC)and colorectal cancer(CRC)can be accomplished through the utilization of data platforms such as TCMSP,SwissTargetPrediction,and PharmMapper.These platforms enable the identification and prediction of potential components and their corresponding targets.Additionally,in order to gather relevant targets specifically associated with GC and CRC,databases such as OMIM,DisGeNET,and GeneCards can be employed.By integrating the results from these data platforms and databases,a comprehensive understanding of the interaction between YFBP and the targets related to GC and CRC can be achieved.To further analyze the interacting targets,the DAVID database platform was utilized to delve into the gene ontology function(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.This step helps in comprehending the functional implications and pathways associated with the identified targets.Subsequently,the Cytoscape software was employed to construct a“compound-target-pathway”network,which visually represents the relationships among the compounds,targets,and pathways.Lastly,to determine the binding ability of the active ingredient to the target protein,molecular docking was performed,providing insights into the potential interactions at a molecular level.Results:From YFBP,a total of 44 active ingredients and 968 action targets were obtained.After intersecting with gastric cancer(GC)and colorectal cancer(CRC),463 intersecting targets were identified.Using the Network Analyzer plugin,10 core components(including acacetin,quercetin,and deoxygenated andrographolide)and 10 core targets(including tumor protein p53,TP53 and AKT)were screened.The gene ontology(GO)analysis revealed that protein phosphorylation was enriched,along with 1870 other entries.The KEGG pathway enrichment analysis identified 195 pathways,including the epidermal growth factor receptor(EGFR)and vascular endothelial growth factor(VEGF)pathways.Furthermore,the molecular docking results provided confirmation of the positive structure-activity relationship observed for acacetin,quercetin,and deoxygenated andrographolide,indicating their potential significance in the therapeutic effects of YFBP.Conclusion:YFBP may regulate signaling pathways such as p53,EGFR,VEGF,and HIF-1 by acting on core targets such as AKT1,TP53,and PIK3CA,exerting the effect of“treating different diseases together”for GC and CRC.