豨莶精醇对免疫性血小板减少症的网络药理学与实验研究

Study on ITP by Darutigenol Based on Network Pharmacology

目的通过网络药理学的方法,研究豨莶精醇对免疫性血小板减少症的作用及作用机制,并通过细胞实验对其作用进行初步探究。方法通过SwissTargetPrediction数据库绘制豨莶精醇结构,预测豨莶精醇作用的靶点,通过GeneCards数据库,以"Immune Thrombocytopenia"为关键词获取疾病相关靶点,通过Cytoscape 3.5.0软件绘制化合物-靶点-疾病网络图,获得豨莶精醇与免疫性血小板减少症共有靶点,使用David 6.8数据库进行GO生物学过程分析和KEGG通路分析,STRING数据库分析获得关键靶点;通过刀豆蛋白A诱导脾细胞增殖,使用豨莶精醇进行干预,检测细胞增殖变化。结果网络药理学分析显示,豨莶精醇与血小板减少性紫癜共有靶点56个,发挥治疗作用的生物学过程与调节多个蛋白通路的磷酸化、调节一氧化氮的合成、调控JAK-STAT级联、调控细胞的增殖凋亡和迁移等相关,涉及的通路有癌症的途径、催乳素信号通路、PI3K-Akt信号通路、ErbB信号通路、胶质瘤、白细胞跨内皮迁移、FoxO信号通路、GnRH信号通路等,关键靶点有STAT3、EGFR、ESR1、HSP90AA1、MAPK8;细胞实验显示豨莶精醇对刀豆蛋白A诱导的脾细胞增殖具有一定的抑制作用。结论豨莶精醇对免疫性血小板减少症具有一定治疗作用,主要的作用机制是通过影响多个基因表达,调节多通路,来影响免疫相关细胞的增殖及凋亡。

Objective To study the effect and mechanism of Darutigenol on ITP by means of network pharmacology and through the cell experiment to explore the effect.Methods The structure of Darutigenol was drawn by SwissTargetPrediction database to predict the target.Through the GeneCards database,disease-related targets were obtained using"Immune Thrombocytopenia"as the keyword,and compound-targets-disease network were drawn by Cytoscape 3.5.0 software,obtained common targets of Darutigenol and ITP,used David 6.8 database for GO biological process analysis and KEGG pathway analysis,STRING database analysis to obtain key targets;Concanavalin A was used to induce the proliferation of splenocytes,and Darutigenol were used to intervene.Results Network pharmacological analysis showed that Darutigenol and ITP share 56 targets,the biological processes that exert therapeutic effects and regulate the phosphorylation of multiple protein pathways,regulate the synthesis of nitric oxide,regulate the JAK-STAT cascade,regulates cell proliferation,apoptosis and migration.The pathways involved are cancer pathway,prolactin signaling pathway,PI3 K-Akt signaling pathway,ErbB signaling pathway,glioma,leukocyte transendothelial migration,FoxO signaling pathway,GnRH signaling pathway,the key targets are STAT3,EGFR,ESR1,HSP90 AA1,and MAPK8;Cell experiment showed that polygonatol could inhibit the proliferation of splenocytes induced by concanavalin A.Conclusion Darutigenol has a certain therapeutic effect on ITP.The main mechanism of action is to affect the proliferation and apoptosis of immune-related cells by influencing the expression of multiple genes and regulating multiple pathways.