首页|基于网络药理学及实验验证探究松三糖治疗肝纤维化的作用机制

基于网络药理学及实验验证探究松三糖治疗肝纤维化的作用机制

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目的 利用网络药理学、分子对接技术研究松三糖治疗肝纤维化潜在机制,并对核心靶点进行实验验证。方法 从Swiss Target Prediction数据库中筛选松三糖治疗疾病相关靶点;从OMIM、GeneCards、Disgenet数据库中筛选出肝纤维化的相关靶点。对STRING数据库进行蛋白质相互作用网络,将tsv格式数据结果导入Cytoscape 3。9。1 软件中进行可视化分析。进一步使用DAVID数据库对交集靶点进行基因本体(GO)分析和京都基因和基因组的百科全书(KEGG)富集分析,并进行分子对接。通过MTT法检测小鼠肝星状细胞系JS-1细胞活力;Western blotting验证核心靶点的蛋白表达水平。结果 KEGG富集分析显示交集靶点涉及信号通路 64 条,主要为磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)、丝裂原活化蛋白激酶(MAPK)信号通路。分子对接提示松三糖与核心靶点能较好结合。Western blotting 结果显示,在不同浓度松三糖作用下,JS-1 细胞中磷酸化的PI3K/Akt以及MAPK的蛋白表达量均显著降低。结论 松三糖可能通过作用于PI3K/Akt及MAPK等多个靶点,发挥抗肝纤维化作用。
Mechanism of melezitose in treatment of liver fibrosis based on network pharmacology and experimental verification
Objective To investigate the mechanisms of the melezitose in treating liver fibrosis using network pharmacology and molecular docking techniques,and to validate the core targets.Methods The related targets of melezitose in treatment of liver fibrosis were screened from the Swiss Target Prediction database.The related targets of liver fibrosis were screened from OMIM,GeneCards and Disgenet databases.The protein interaction network was carried out on the STRING database,and the tsv format data results were imported into Cytoscape 3.9.1 software for visual analysis.DAVID database was further used for GO analysis and KEGG enrichment analysis,and molecular docking.The viability of mouse hepatic stellate cell line JS-1 was measured by MTT assay.Western blotting verified the protein expression level of the core target.Results KEGG enrichment analysis showed that the intersection targets involved 64 signaling pathways,mainly PI3K/Akt and MAPK signaling pathways.Molecular docking suggested that pine triose could bind well to the core target.Western blotting results showed that the phosphorylated PI3K/Akt and MAPK protein expressions in cells were significantly reduced under the influence of different concentrations of melezitose.Conclusion Melezitose may exert anti-liver fibrosis effects by acting on multiple targets such as PI3K/Akt and MAPK.

melezitoseliver fibrosisnetwork pharmacologymolecular dockingPI3K/AktMAPK

吕志远、宋建忠、曹玲玲、向阳、李进发、常军民

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新疆医科大学 药学院,新疆 乌鲁木齐 830000

新疆医科大学附属肿瘤医院 药学部,新疆 乌鲁木齐 830011

新疆医科大学 基础医学院,新疆 乌鲁木齐 830000

新疆医科大学第一附属医院 检验科,新疆 乌鲁木齐 830011

新疆天然药物活性组分与释药技术重点实验室,新疆 乌鲁木齐 830000

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松三糖 肝纤维化 网络药理学 分子对接 磷脂酰肌醇3-激酶 蛋白激酶B 丝裂原活化蛋白激酶

新疆维吾尔自治区重大科技专项项目新疆维吾尔自治区自然科学基金资助项目

2022A03019-32022D01D37

2024

现代药物与临床
天津药物研究院,中国药学会

现代药物与临床

CSTPCD
影响因子:1.179
ISSN:1674-5515
年,卷(期):2024.39(10)
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