文献类型：期刊文献

中文题名：基于网络药理学及实验验证探究廖氏化风丹抗白血病活性

英文题名：Exploring the Anti-leukemia Activity of Liaoshi Huafeng Dan Based on Network Pharmacology and Experimental Verification

作者：黄丽荣 程莎 侯菁 余佳 宋玉 万小青 滕彩厚 徐应江 骆衡

第一作者：黄丽荣

机构：[1]贵州理工学院食品药品制造工程学院,贵州贵阳550003;[2]贵州医科大学药用植物功效与利用国家重点实验室,贵州贵阳550014;[3]贵州省天然产物研究中心,贵州贵阳550014;[4]贵州万胜药业有限责任公司,贵州遵义563005

第一机构：贵州理工学院食品药品制造工程学院

年份：2023

卷号：34

期号：11

起止页码：1575-1585

中文期刊名：中药新药与临床药理

外文期刊名：Traditional Chinese Drug Research and Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：贵州理工学院高层次人才科研启动经费项目(XJGC20190659);贵州省科技支撑计划项目(黔科合支撑[2020]4Y161、黔科合支撑[2021]一般412);贵州省“百”层次创新型人才培养项目(黔科合平台人才-GCC[2022]034-1)。

语种：中文

中文关键词：廖氏化风丹;白血病;网络药理学;分子对接;实验验证;HEL细胞;K562细胞;小鼠

外文关键词：Liaoshi Huafeng Dan;leukemia;network pharmacology;molecular docking;experimental verification;HEL cells;K562 cells;mice

摘要：目的基于网络药理学探究廖氏化风丹抗白血病活性及作用机制,并通过实验进行验证。方法采用气相色谱-质谱联用分析结合中药系统药理学数据库与分析平台检索廖氏化风丹的化学成分;应用Swiss Target Prediction数据库检索该成分的潜在作用靶点;通过数据库GeneCards、CTD和OMIM检索白血病相关靶点;使用STRING数据库对交集靶点进行互作分析,构建PPI网络,筛选核心靶点;借助Cytoscape 3.8.0软件构建“药物-成分-靶点”网络,分析抗白血病关键活性成分;应用DAVID数据库进行基因本体(GO)功能富集与京都基因和基因组百科全书(KEGG)通路注释分析,将得到的主要活性成分与核心靶蛋白进行分子对接验证。采用MTT实验检测廖氏化风丹对白血病细胞增殖的影响,流式细胞术检测其对白血病细胞凋亡的影响;构建白血病小鼠模型,通过动物实验检测廖氏化风丹体内抗白血病活性。结果分析确定了廖氏化风丹活性成分111个,作用靶点1170个,其中与白血病相关的潜在靶点970个,核心靶点10个,主要包括ABL、BCL-2、KIT等;GO富集分析与KEGG注释分析显示这些作用靶点主要参与细胞凋亡、细胞增殖的调控等生物过程及cAMP信号通路、癌症通路、神经活性配体-受体相互作用、PI3K-Akt信号通路等;分子对接结果显示廖氏化风丹核心活性成分与核心靶蛋白ABL、BCL-2、KIT有较强的亲和力;体外细胞实验表明廖氏化风丹能够抑制HEL、K562细胞增殖并诱导细胞凋亡(P<0.01);动物体内实验结果表明廖氏化风丹对小鼠白血病有明显治疗作用(P<0.05,P<0.01)。结论揭示了廖氏化风丹抗白血病多成分、多靶点、多通路的作用机制,明确了其具有抗白血病活性,为进一步研究开发廖氏化风丹的药用价值提供依据。
Objective To investigate the anti-leukemia activity and mechanism of Liaoshi Huafeng Dan based on network pharmacology and experimental verification.Methods Gas chromatography-mass spectrometer analysis and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to search the chemical constituents of Liaoshi Huafeng Dan.The Swiss Target Prediction database was used to search the potential targets of components.Leukemia-related targets were retrieved from GeneCards,CTD and OMIM databases.The STRING database was used to analyze the interaction between the intersecting targets,the PPI network was constructed,and the core targets were screened.Cytoscape 3.8.0 sofware was used to construct a"drugscomponents-targets"network to analyze the key active components for anti-leukemia activity.DAVID database was used for GO enrichment and KEGG pathway annotation analysis,and molecular docking verification was conducted between the main active components and core target proteins.MTT assay was used to detect the effect of Liaoshi Huafeng Dan on the proliferation of leukemia cells,and the flow cytometry was used to detect the effect on the apoptosis of leukemia cells.The anti-leukemic activity of Liaoshi Huafeng Dan was detected in vivo by animal experiment.Results A total of 1ll active ingredients and 1170 targets of Liaoshi Huafeng Dan were identified,970 potential targets related to leukemia and 10 core targets were obtained,including ABL,BCL-2,KIT.GO enrichment analysis and KEGG pathway enrichment analysis showed that these targets were mainly involved in biological processes such as regulation of apoptosis and cell proliferation,cAMP signaling pathway,cancer pathway,neural active ligand-receptor interaction,and PI3K-Akt signaling pathway.The molecular docking results showed that the core active components of Liaoshi Huafeng Dan had strong affinity for the core target proteins,including ABL,BCL-2 and KIT.The cell experiments in vitro showed that Liaoshi Huafeng Dan could inhibit the proliferation and induce apoptosis of HEL and K562 cells(P<0.01).The animal experiments indicated that Liaoshi Huafeng Dan has significant therapeutic effect on mouse erythroleukemia(P<0.05,P<0.01).Conclusion This study revealed the mechanism of multi-component,multi-target and multi-channel for Liaoshi Huafeng Dan in the treatment of leukemia.Its anti-leukemia activity was confirmed,which provided basis for further research and development of medicinal value of Liaoshi Huafeng Dan.