基于网络药理学与体外实验探讨木犀草素治疗乳腺炎的作用机制  

Action mechanism of luteolin in the treatment of mastitis based on network pharmacology and in vitro experiments

作　　者：李月平 陈晓兰 谢树才 姜林丽 谌文元 LI Yueping;CHEN Xiaolan;XIE Shucai;JIANG Linli;CHEN Wenyuan(School of Pharmacy,Guizhou Universityof Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学药学院,贵州贵阳550025

出　　处：《贵州科学》2025年第1期51-60,共10页Guizhou Science

摘　　要：目的:基于网络药理学与体外验证实验探讨木犀草素防治乳腺炎(Mastitis)的相互作用机理。方法:依托TCMSP、Swiss Target Prediction、Gene Cards等数据库系统对木犀草素与乳腺炎相关的靶点做出预测,在STRING数据库系统中取两者交叉靶点构建蛋白相互作用(PPI)网络系统,并借助于CytosCape3.7.软件系统开展可视化数据分析,检测出核心靶点。使用David数据库经过GO和KEGG富集解析,预测木犀草素防治乳腺炎的功能机理,经过分子对接技术和牛乳腺上皮细胞(BMECS)实验验证。结果:预测发现,有314个木犀草素潜在靶点和186个乳腺炎潜在靶点,两者有16个交叉靶点,涉及ICAM1、ERBB、EGFR、ESR1、IL6、TNF等6个重要核心基础靶点。根据GO的分析结果,涉及生物过程的有负调节的凋亡进程、正调节的RNA聚合酶Ⅱ启动子转录、基因组表现的正调节等,这些都是生物过程的重要组成部分。研究表明,DNA结合是一种特殊的分子机制,它可以影响蛋白质、酶、细胞因子、蛋白激酶、雌激素反应元件以及RNA聚合酶Ⅱ转录因子等多种生物学功能,而且它们之间还可以通过配体调节DNA的激活序列,从而发挥出其独特的作用。细胞外空间、细胞表面、线粒体基质等涉及细胞组分。在KEGG途径中,主要有癌症途径、脂质及动脉粥样硬化信号途径、甲型流感途径、JAK-STAT信号途径、PI3K-AKT信号途径、蛋白聚糖、乳癌、EGFR酪氨酸激酶抑制剂抗药性信号途径等。分子对接结果显示,木犀草素与ICAM1、ERBB2、EGFR、ESR1、IL6、TNF等6个核心靶点均具有良好的结合活性。经过实际应用,我们发现,DMSO的浓度为0.5%时,可以使细胞的生存率提升至95.04%。相比之下,LPS的浓度降至10μg·mL^(-1)时,可以使其生长受限。我们还发现,在24 h的情况下,10μg·mL^(-1)的LPS可以有效地影响BMEC细胞,并使其产生更多的TNF-α。低、中、高剂量木犀草素分别为:In this study we investigated the interaction mechanism of luteolin in the prevention and treatment of mastitis based on network pharmacology and in vitro validation experiments.The targets related to luteolin and mastitis were predicted by using TCMSP,Swiss Target Prediction,Gene Cards and other databases,and the protein interaction(PPI)network was constructed by taking the cross-targets of the two in STRING database.The visual data analysis was carried out with the help of CytosCape3.7.software to detect the core targets.GO and KEGG enrichment analysis were performed by using David database,and the functional mechanism of luteolin in the prevention and treatment of mastitis was predicted.The results were verified by molecular docking and bovine mammary epithelial cell(BMECS)experiment.It was predicted that there were 314 potential targets of luteolin and 186 potential targets of mastitis,and 16 cross-targets were found,involving 6 important core basic targets,including ICAM1,ERBB,EGFR,ESR1,IL6 and TNF.According to GO results,the negatively regulated apoptosis process,positively regulated RNA polymerase Ⅱ promoter transcription,and positively regulated genomic expression were involved.Among the KEGG pathways,there were mainly cancer pathway,lipid and atherosclerotic signaling pathway,influenza A pathway,JAK-STAT signaling pathway,PI3K-AKT signaling pathway,proteoglycan,breast cancer,EGFR tyrosine kinase inhibitor resistance signaling pathway,etc.The molecular docking results showed that luteolin had good binding activity with six core targets,including ICAM1,ERBB2,EGFR,ESR1,IL6 and TNF.After practical application,we found that 0.5%DMSO could increase the survival rate of cells to 95.04%.In contrast,10μg/mL LPS could limit its growth.We also found that at 24 h,10μg/mL LPS could effectively affect BMEC cells and cause them to produce more TNF-α.Low-,medium-,and high-dose luteolin were 1μg/mL,10μg/mL,and 20μg/mL,respectively,and the concentration of the positive drug dexamethasone was 0.1μg/mL.Compared wit

关 键 词：木犀草素 乳腺炎 网络药理学 分子对接 Janus激酶-转录激活因子信号通路 

分 类 号：R285.5[医药卫生—中药学]