基于网络药理学和分子对接探究浙贝母治疗急性髓系白血病的作用机制

Study of the Mechanism of Zhebeimu(Fritillaria thunbergii)in the Treatment of Acute Myeloid Leukemia based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接,初步探寻浙贝母治疗急性髓系白血病(AML)作用机制。方法:通过TCMSP数据库联合Swiss Target Prediction数据库,筛选浙贝母化学成分并预测相关靶点,通过GeneCards、OMIM、DRUGBANK数据库获取急性髓系白血病靶点,取二者交集基因利用String平台进行蛋白质相互作用分析,采用DAVID平台对其进行GO和KEGG富集分析,使用CytoScape3.7.2软件构建(化学成分-靶点-通路)网络图,同时筛取浙贝母靶点基因与GEO数据库急性髓系白血病差异基因的交集基因,将前后所得的交集基因通过分子对接验证。结果:分子对接结果显示,浙贝母治疗AML的核心化学成分为6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-吡喃葡萄糖、紫鄂贝碱、β-谷甾醇、浙贝母甲素、浙贝母乙素,核心靶点为CYP1B1、PTGS2、GAPDH、CCND1。主要通过细胞凋亡、细胞增殖、代谢、免疫调节、促血管生长等生物学通路发挥作用。结论:本研究初步揭示了浙贝母通过多成分、多靶点、多通路治疗急性髓系白血病的作用机制,其小分子化合物6-甲氧基-2-乙酰基-3-甲基-1,4-萘醌-8-O-β-D-吡喃葡萄糖对CYP1B1靶点的调节作用为浙贝母发挥其治疗功能的关键机制,为下一步的实验研究提供了方向。

Objective:To explore the mechanism of Zhebeimu(Fritillaria thunbergii)in the treatment of acute myeloid leukemia(AML)based on network pharmacology and molecular docking.Methods:TCMSP database and Swiss Target Prediction database were used to screen chemical constituents and predict related targets.Genecards,OMIM and DRUGBANK databases were used to obtain acute myeloid leukemia targets.Protein interaction analysis was performed by string platform for the intersection genes,and GO and KEGG enrichment analysis were performed by DAVID platform.The software of CytoScape 3.7.2 was used to construct the(chemical composition target pathway)network map.Meanwhile,the intersection genes between target genes of Zhebeimu(Fritillaria thunbergii)and different genes of acute myeloid leukemia in geo database were screened,and the obtained intersection genes were verified by molecular docking.Results:The results of molecular docking showed that the core chemical components of Zhebeimu(Fritillariae)in the treatment of AML were 6-methoxyl-2-acetyl-3-methyl-1,4-naphthoquinone-8-O-beta-D-glucopyra-noside,Ziebeimine,beta-sitosterol,Verticine,Peiminine.The core targets were CYP1B1,PTGS2,GAPDH and CCND1.It played an important role in cell apoptosis,proliferation,metabolism,immune regulation,vascular growth and other biological pathways.Conclusion:This study preliminarily revealed the mechanism of Zhebeimu(Fritillaria thunbergii)in the treatment of acute myeloid leukemia through multi-component,multi-target and multi-channel,and the regulatory effect of its small molecule compound 6-methoxy-2-acetyl-3-methyl-1and 4-naphthoquinone-8-o-beta-D-glucopyranose on CYP1B1 target was the key mechanism for Zhebeimu(Fritillaria thunbergii)to play its therapeutic function,and provides the direction for further experimental research.