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基于网络药理学探讨藤梨根治疗结直肠癌的作用机制

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目的 基于网络药理学的研究方法探讨中药藤梨根治疗结直肠癌的作用机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)以及中医药整合药理学研究平台(TCMIP)获取藤梨根的主要活性成分和药物作用靶点,通过GeneCards数据库和OMIM数据库获取结直肠癌的疾病靶点,再通过R语言及VennDiagram作图数据包映射筛选得出药物与疾病的交集靶点,即为藤梨根治疗结直肠癌的潜在治疗靶点.利用Cytoscape 3.7.1 软件、String 数据库分别构建藤梨根治疗结直肠癌的潜在治疗靶点的"药物-成分-疾病-靶点"网络图和蛋白质-蛋白质相互作用(PPI)网络图.最后通过David数据库对潜在治疗靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将富集结果可视化.结果 筛选到藤梨根药物主要活性成分 6 个,药物作用靶点 154 个,结直肠癌相关疾病靶点10 622 个,两者取交集得到藤梨根治疗结直肠癌的潜在治疗靶点145 个;藤梨根的6 种活性成分芦荟大黄素(aloe-emodin)、ent-表儿茶素(ent-Epicatechin)、(+)-儿茶素[(+)-catechin]、槲皮素(quercetin)、谷甾醇(sitos-terol)及β-谷甾醇(beta-sitosterol)均为治疗结直肠癌的关键核心成分,关键靶点有丝氨酸/苏氨酸蛋白激酶 1(AKT1)、白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、JUN、胱天蛋白酶 3(CASP3)、IL-1β、表皮生长因子受体(EGFR)、ESR1 等;GO功能富集分析结果共得到生物过程(BP)条目 141 个,主要涉及DNA结合转录因子活性、转录因子活性、细胞因子活性、血红素结合抗氧化活性等生物过程,KEGG通路富集分析结果显示主要涉及晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路、肿瘤坏死因子(TNF)信号通路、IL-17 信号通路、缺氧诱导因子-1(HIF-1)信号通路等.结论 基于网络药理学的角度初步探讨并验证了藤梨根治疗结直肠癌的多成分、多靶点、多通路的整体调节作用特点,预测了藤梨根治疗结直肠癌的潜在作用机制,为其活性成分研究与实验研究提供科学依据.
Mechanism of Radix Actinidiae chinensis in treating colorectal cancer based on the network pharmacology
Objective To explore the therapeutic mechanism of the traditional Chinese medicine(TCM)herbal Radix Actinidiae chinensis in the treatment of colorectal cancer(CRC)based on the network pharmacology.Methods The main ac-tive ingredients and drug targets of Radix Actinidiae chinensis were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine(TCMIP).Disease targets of CRC were predicted using the GeneCards database and the Online Mendelian Inheritance in Man(OMIM).The intersection of drug targets and disease targets was obtained using the R package and visualized in a Venn diagram,which were therapeutic targets of Radix Actinidiae chinensis in the treatment of CRC.Cyto-scape3.6.1 software and String database were used to construct the drug-component-disease-target network and protein-protein interaction(PPI)network.Finally,therapeutic targets of Radix Actinidiae chinensis in the treatment of CRC were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)enrichment analyses,and visualized using the Database for Annotation,Visualization and Integrated Discovery(DAVID).Results A total of 6 active ingredients and 154 disease targets of Radix Actinidiae chinensis,and 10 622 disease targets associated with CRC were screened.By making an intersection,145 therapeutic targets of Radix Actinidiae chinensis in the treatment of CRC were obtained.The six active ingredients of Radix Actinidiae chinensis,including aloe-emodin,ent-Epicatechin,(+)-catechin,quercetin,sitosterol and beta-sitosterol were all the core targets for the treatment of CRC.Key targets included AKT1(AKT Serine/Threonine Kinase 1),IL-6(interleukin 6),VEGFA(Vascular Endothelial Growth Fac-tor A),JUN(Jun proto-oncogene),CASP3(caspase-3),IL-1β(interleukin 1β),EGFR(epidermal growth factor recep-tor)and ESR1(estrogen receptor 1).GO enrichment analysis obtained 141 terms of biological processes(BP),mainly inclu-ding the DNA-binding transcription factor activity,transcription factor activity,cytokine activity and heme-binding antioxidant activity.The KEGG pathway enrichment analysis showed that the core targets were mainly enriched in the AGE-RAGE(Ad-vanced Glycation End Products and receptor for AGEs),TNF(tumor necrosis factor),IL-17(interleukin 17)and HIF-1(Hypoxia-Inducible Factor 1)signaling pathways.Conclusion Based on the network pharmacology,we primarily explore and verifie the multi-component,multi-target and multi-pathway therapeutic regulation of Radix Actinidiae chinensis in CRC,predict the potential of Radix Actinidiae chinensis in the treatment of CRC,and provide scientific references for analyzing its ac-tive ingredients and experimental research.

Radix Actinidiae chinensisColorectal cancerPharmacology of chinese medicineMechanism

吴赛、王馨璐、陆玮兰、汪海慧、李海涛、闫国良

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上海中医药大学,上海 201203

上海中医药大学附属市中医医院急诊科,上海 200071

藤梨根 结直肠癌 中药药理 作用机制

上海市卫生和计划生育委员会科研课题计划

201740012

2024

河北中医
河北省医学情报研究所,河北省中医药学会

河北中医

CSTPCD
影响因子:0.951
ISSN:1002-2619
年,卷(期):2024.46(1)
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