基于网络药理学和分子对接探讨诃子缓解乌头碱引起的神经毒性机制研究

Study on the mechanism of Chebulae Fructus in alleviating aconitine-induced neurotoxicity based on network pharmacology and molecular docking

目的:采用网络药理学方法分析诃子缓解乌头碱引起的神经毒性的可能机制。方法:使用网络药理学数据库得到诃子缓解乌头碱神经毒性的成分和靶点。对得到的靶点进行蛋白相互作用分析,筛选出诃子缓解乌头碱引起神经毒性的关键成分和靶点,并使用分子对接进行验证。应用Metascape数据库对交集中靶点进行GO分析和KEGG通路富集。结果:筛选出诃子中11种成分和150个靶点,其中鞣花酸、碎叶紫堇碱、硫酸奎尼丁、番泻苷E_qt、霹雳萝芙辛碱五个关键成分与ALB、EGFR、HSP90AA1、SRC、CASP3五个关键靶点之间可以通过极性作用紧密结合。靶点的富集分析显示诃子缓解乌头碱引起神经毒性靶点存在于轴突、树突、细胞体、细胞外基质、线粒体基质等部位,可能参与抗氧化活性、ATP酶结合等功能,可能调节FoxO,PI3K-Akt,Ras,MAPK等信号传导通路。结论:诃子治疗乌头碱神经毒性可能与调节神经系统中氧化应激反应,调节神经细胞中线粒体相关的能量代谢,调节神经递质传递等机制有关。

Objective:To analyze the potential mechanism of Chebulae Fructus in alleviating aconitine-induced neurotoxicity using the network pharmacology method.Method:The components and targets of Chebulae Fructus in alleviating aconitineinduced neurotoxicity were obtained by using network pharmacological databases.Protein-protein interaction analysis was conducted on the obtained targets,and the key components and targets of Chebulae Fructus alleviating aconitine-induced neurotoxicity were screened,which were validated by molecular docking.GO analysis and KEGG enrichment analysis of the interaction targets were conducted through the Metascape database.Result:11 components and 150 targets of Chebulae Fructus were screened,among which the five key components including(R)-(6-methoxy-4-quinolyl)-[(2R,4R,5S)-5-vinylquinuclidin-2-yl]methanol,Cheilanthifoline,Ellagic acid,Sennoside E_qt and Peraksine could closely bind to the five key targets including ALB,EGFR,HSP90AA1,SRC and CASP3 by polarity interaction.Enrichment analysis of the targets showed that the targets of Chebulae Fructus alleviating aconitine-induced neurotoxicity existed in axons,dendrites,cell bodies,extracellular matrix and mitochondrial matrix,which may be involved in antioxidant activity,ATPase binding and other functions,and may regulate the FoxO,PI3K-Akt,Ras,MAPK signaling pathways.Conclusion:The mechanism of Chebulae Fructus in alleviating aconitineinduced neurotoxicity may be related to regulating oxidative stress responses in the nervous system,mitochondria-related energy metabolism in nerve cells,and neurotransmitter transmission.