摘要
目的:探究中医药治疗急性淋巴细胞白血病(ALL)的作用机制,并用实验验证。方法:收集中医药治疗ALL文献的药物组成;利用中药系统药理学数据库与分析平台(TCMSP)、通用蛋白质(UniProt)数据库收集高频中药的成分及靶点,基因表达综合系统(GEO)数据库收集疾病靶点,取交集靶点,利用微生信平台进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析,利用Cytoscape 3.9.1构建蛋白质-蛋白质相互作用网络(PPI);基于网络药理学预测结果,用分子对接及实验进行验证。结果:筛选得到10个高频中药,包含157个有效成分及280个靶点,ALL相关的疾病靶点2428个,经筛选得到37个交集靶点,KEGG富集分析显示交集靶点作用于白细胞介素-17(IL-17)、化学致癌受体激活、T细胞受体等多种癌症、免疫和炎症反应相关的信号通路,核心有效成分为槲皮素,核心靶点为蛋白激酶B(AKT1),分子对接结果显示二者对接良好,细胞实验结果显示槲皮素处理后的ALL细胞活率明显降低,凋亡率明显升高(P<0.05),磷脂酰肌醇3-激酶(PI3K)、磷酸化蛋白激酶B(p-AKT)的表达均降低。结论:网络药理学的初步筛选与预测发现,中药可通过多成分、多靶点、多通路治疗ALL,其中的核心成分槲皮素可通过调控PI3K/AKT信号通路抑制ALL细胞增殖、诱导细胞凋亡,从而发挥抗ALL的作用,为中药治疗ALL有效成分的开发和运用提供参考。
Objective:To explore the mechanisms of traditional Chinese medicine(TCM)in the treatment of acute lymphoblastic leukemia(ALL)and to validate these findings through experiments.Methods:A literature review was conducted to collect the medicinal compositions used in TCM for ALL treatment.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the UniProt database were utilized to gather high-frequency TCM components and their targets.Disease-related targets were obtained from the Gene Expression Omnibus(GEO)database,and intersection targets were identified.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the Microarray Analysis Platform.A protein-protein interaction(PPI)network was constructed using Cytoscape 3.9.1.Based on network pharmacology predictions,molecular docking and experimental validation were carried out.Results:Ten high-frequency TCMs were identified,comprising 157 active components and 280 targets,with 2428 disease-related targets for ALL.After filtering,37 intersection targets were obtained.KEGG enrichment analysis indicated that these targets were involved in multiple cancer,immune,and inflammatory response-related signaling pathways,including interleukin-17(IL-17),chemokine receptor activation,and T-cell receptor pathways.The core active component identified was quercetin,with the key target being protein kinase B(AKT1).Molecular docking results showed a good interaction between quercetin and AKT1.Cell experiments demonstrated that quercetin treatment significantly reduced the viability of ALL cells and increased apoptosis rates(P<0.05),with a decrease in the expression of phosphoinositide 3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT).Conclusion:Preliminary screening and predictions from network pharmacology indicate that TCM can treat ALL through multiple components,targets,and pathways.The core component quercetin may inhibit ALL cell proliferation and induce ap
作者
刘景文
马秋玲
苏雅静
石慧慧
郭家缘
张曼
刘洺欣
李东东
刘文卿
LIU Jingwen;MA Qiuling;SU Yajing;SHI Huihui;GUO Jiayuan;ZHANG Man;LIU Mingxin;LI Dongdong;LIU Wenqing(The Second Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450002,China)
出处
《世界中医药》
CAS
北大核心
2024年第17期2562-2571,共10页
World Chinese Medicine
基金
国家自然科学基金青年科学基金项目(82204981)
河南省自然科学基金项目(222300420487)
河南省中医药科学研究专项(20-21ZY1050)
河南省中医药科学研究专项课题(2022ZY1056)。
关键词
急性淋巴细胞白血病
中医药
有效成分
网络药理学
细胞实验
加权基因共表达网络分析
分子对接
作用机制
Acute lymphocytic leukemia
Traditional Chinese medicine
Active ingredients
Network pharmacology
Cell experiments
Weighted gene co expression network analysis
Molecular docking
Mechanism of action
