基于网络药理学消岩汤中夏枯草与白花蛇舌草治疗非小细胞肺癌作用机制的研究

Network Pharmacology Studies on Therapeutic Mechanism of Spica Prunellae and Herba Hedyotis Diffusae in Xiaoyan Decoction for the Treatment of Non-Small Cell Lung Cancer

目的运用网络药理学方法探讨消岩汤中夏枯草与白花蛇舌草治疗非小细胞肺癌的功效物质基础和作用机制。方法运用中药系统药理学分析平台(traditional Chinese medicine systems phannacology,TCMSP)检索消岩汤中夏枯草与白花蛇舌草两味中药的活性化合物与作用靶点,通过Online Mendelian Inheritance in Man(OMIM)、Genecards、PharmGkb以及治疗靶点数据库(Therapeutic Target Database,TTD)疾病数据库查找非小细胞肺癌的相关靶点,绘制“药物-共同靶点-疾病”网络图,将夏枯草和白花蛇舌草两味中药和非小细胞肺癌的共同靶点,进行蛋白互作网络(protein-protein interaction network,PPI)分析,并进行基因本体(Gene Ontology,GO)与京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果按口服生物利用度(oral bioavailability,OB)≥30%且类药性(drug likeness,DL)≥0.18作为筛选标准,得出两味中药的活性化合物共有15种,作用靶点有160个;以“药物靶点-疾病靶点”高相关性为标准,筛选出非小细胞肺癌一共有2513个疾病靶点,药物与疾病的共同靶点一共有112个。PPI互作关系最多的靶点为蛋白激酶B(protein kinase,AKT)1、白介素(Interleukin,IL)-6、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)A、重组人半胱天冬酶(Caspase,CASP)-3、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)。GO富集共包含1476条结果,提示共同靶点的功能主要表现在对氧化应激的反应相关通路,KEGG富集显示,共同靶点表达在151条信号通路中。结论阐明了消岩汤中夏枯草与白花蛇舌草是通过多成分、多靶点发挥对非小细胞肺癌的治疗作用,且作用机制与HIF-1信号通路以及对氧化应激反应相关通路有紧密联系,为消岩汤的临床应用和实验研究提供了科学依据。

Objective Network pharmacology studies were carried out to explore the active substance and therapeutic mechanism of Spica Prunellae and Herba Hedyotis Diffusae in Xiaoyan Decoction for the treatment of non-small cell lung cancer(NSCLC).Methods Active compounds and therapeutic targets related to Spica Prunellae and Herba Hedyotis Diffusae in Xiaoyan Decoction were retrieved from the analysis platform of traditional Chinese medicine systems pharmacology(TCMSP)database.By using the disease-related databases of Online Mendelian Inheritance in Man(OMIM), Genecards, PharmGkb and Therapeutic Target Database(TTD), we searched for targets relevant to NSCLC and established the network diagram of “medicine- common targets diseases”. By combining the common targets of Spica Prunellae and Herba Hedyotis for NSCLC,we constructed their protein-protein interaction network(PPI),and then completed the Gene Ontology(GO)analysis and KEGG enrichment analysis. Results With the oral bioavailability(OB)≥ 30% and drug likeness(DL)≥ 0.18 as the selection criteria, 15 active ingredients and 160 acting targets were screened from Spica Prunellae and Herba Hedyotis in Xiaoyan Decoction. With the high correlation of medicine to diseases as the standard,a total of 2 513 high-correlation targets of NSCLC and 112 common targets relevant with drugs and diseases were screened out. PPI network was constructed,and then the most common targets were protein kinase AKT1,interleukin 6(IL-6), vascular endothelial growth factor A(VEGFA),human recombinant CASP3 and epidermal growth factor receptor (EGFR). A total of 1 476 results were obtained after the GO enrichment analysis,indicating that the function of the common target was mainly manifested as the oxidative stress-related pathway. The KEGG enrichment analysis showed that the common target was expressed in 151 signal pathways. Conclusion The network pharmacology studies indicated that the effect of Spica Prunellae and Herba Hedyotis Diffusae in Xiaoyan Decoction on NSCLC is through multiple components and multiple targets, and the therapeutic mechanism is closely related with the hypoxia inducible factor 1(HIF-1)signal pathway and with the oxidative stress-related pathway. The results will provide scientific basis for the clinical application and experimental research of Xiaoyan Decoction.