基于网络药理学及分子对接探讨三七治疗胃癌前病变的作用机制

Mechanism of Notoginseng Radix et Rhizoma in treatment of gastric precancerous lesions based on network pharmacology and molecular docking

目的基于网络药理学及分子对接方法探讨三七治疗胃癌前病变机制。方法通过中药系统药理学数据库与分析平台(TCMSP)筛选三七有效成分和靶点,通过Uniprot数据库将获取的蛋白靶点转换为人类基因靶点,通过SwissTarget Prediction数据库进行成分潜在靶点预测补充。通过GeneCards数据库筛选胃癌前病变疾病相关靶点。筛选出三七治疗胃癌前病变交集靶点利用STRING数据库与Cytoscape 3.9.1软件构建蛋白质相互作用(PPI)网络。利用David数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;运用AutoDock vina对三七有效成分(配体)与核心靶点(受体)进行分子对接,利用PyMOL软件将结果进行可视化处理。结果共收集到三七8种有效成分及三七治疗胃癌前病变的交集靶点128个;三七治疗胃癌前病变的5个最核心靶点分别为信号转导及转录激活蛋白3(STAT3)、丝裂原活化蛋白激酶1(MAPK1)、肿瘤蛋白P53(TP53)、蛋白激酶B(Akt1)、90KDA热休克蛋白ΑA1重组蛋白(HSP90AA1),2个核心有效活性成分为槲皮素和人参皂苷F2。GO富集分析显示,相关靶点参与基因调控、细胞凋亡、DNA及RNA转录等多个生物学过程发挥作用。KEGG富集分析显示,三七治疗胃癌前病变在癌症通路富集最明显,核心靶点还参与了包括Janus激酶-信号转导及转录激活因子(JAK/STAT)、MAPK、TP53、磷脂肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路在内的多种信号通路途径发挥作用。结论三七治疗胃癌前病变具有多成分、多靶点、多通路的特点,机制复杂,可能主要通过癌症通路途径发挥作用。

Objective To explore the mechanism of Notoginseng Radix et Rhizoma for the treatment of gastric precancerous lesions based on network pharmacology and molecular docking methods.Methods To screen Notoginseng Radix et Rhizoma active ingredients and targets by TCMSP,the protein targets obtained were converted into human gene targets through the Uniprot database,and the potential targets of ingredients were predicted and supplemented through the SwissTargetPrediction database.To screen the gastric precancerous lesions disease-related targets through Genecards database.The protein interaction(PPI)network was constructed using STRING database and Cytoscape 3.9.1 software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using David database.AutoDock vina was used to molecularly dock the active ingredients(ligands)of Notoginseng Radix et Rhizoma with the core targets(receptors).Results A total of 8 effective components of Notoginseng Radix et Rhizoma and 128 intersectional targets of Panax notoginseng in treatment of gastric precancerous lesions were collected.The five core targets of Notoginseng Radix et Rhizoma in treatment of gastric precancerous lesions were signal transduction and transcription-activating protein 3(STAT3),mitogen activated protein kinase 1(MAPK1),tumor protein P53(TP53),protein kinase B(Akt1),and 90KDA heat shock proteinΑA1 recombinant protein(HSP90AA1).The two core active ingredients were quercetin and ginsenoside F2.GO enrichment analysis showed that related targets played a role in many biological processes,such as gene regulation,cell apoptosis,DNA and RNA transcription.KEGG enrichment analysis showed that Notoginseng Radix et Rhizoma had the most obvious enrichment in the cancer pathway in treatment of gastric prelesions.Core targets are also involved in various signaling pathways,including the Janus kinase-signal transduction and transcriptional activator(JAK/STAT),MAPK,TP53,and phospholipinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway.Conclusion Notoginseng Radix et Rhizoma has the characteristics of multicomponent,multi-target and multi-pathway in the treatment of gastric precancerous lesions,and its mechanism is complex,which may play its role mainly through the cancer pathway.