首页|期刊导航|药学研究|基于数据挖掘和网络毒理学探究苦参碱诱发癫痫发作的作用机制

基于数据挖掘和网络毒理学探究苦参碱诱发癫痫发作的作用机制OA

Exploring the mechanism of matrine-induced epileptic seizures based on data mining and network toxicology

中文摘要英文摘要

目的 探究苦参碱诱发癫痫发作的潜在作用机制,为其神经毒性研究提供理论依据.方法 基于数据挖掘和网络毒理学方法,整合苦参碱与癫痫相关靶点,对交集靶点进行富集分析,进一步结合蛋白质互作网络、机器学习等方法筛选核心毒理生物标志物,并利用分子对接验证苦参碱与标志物的结合活性.结果 共筛选出 63个苦参碱诱导癫痫的潜在作用靶点.富集分析表明其主要参与铁死亡、Janus 激酶-信号转导和转录激活因子(JAK-STAT)信号通路、白细胞介素-17(IL-17)信号通路等关键分子途径.最终确定了 5 个核心毒理生物标志物(SQSTM1、NFE2L2、JAK2、Akt1 和 BCL2).同时分子对接结果显示苦参碱与核心靶点均具有良好的结合活性.结论 苦参碱可能通过作用于 SQSTM1、NFE2L2、JAK2 等核心靶点,调控铁死亡、JAK-STAT 及 IL-17 信号通路等多条途径,协同诱发癫痫发作.本研究为阐明苦参碱的神经毒性机制及潜在干预策略提供了新思路和理论依据.

Objective To explore the potential mechanism of matrine-induced epileptic seizures and provide a theoreti-cal basis for its neurotoxicity research.Methods Based on data mining and network toxicology methods,the targets related to matrine and epilepsy were integrated,and the enrichment analysis of their intersection targets was conducted.Further,mul-tiple methods such as protein-protein interaction networks and machine learning were combined to screen core toxicological biomarkers.Molecular docking was utilized to verify the binding activity of matrine with the biomarkers.Results A total of 63 potential targets of matrine-induced epilepsy were screened out.Enrichment analysis indicated that they mainly participa-ted in key molecular pathways such as ferroptosis,JAK-STAT signaling pathway,and IL-17 signaling pathway.Eventually,five core toxicological biomarkers(SQSTM1,NFE2L2,JAK2,Akt1,BCL2)were determined.Meanwhile,the molecular docking results showed that matrine had good binding activity with the core targets.Conclusion Matrine may induce epi-leptic seizures by acting on core targets such as SQSTM1,NFE2L2,and JAK2,and regulating multiple pathways including ferroptosis,JAK-STAT,and IL-17 signaling pathways in a coordinated manner.This study provides new ideas and theoretical basis for clarifying the neurotoxic mechanism of matrine and potential intervention strategies.

任姿瑄;李昌玲;刘德山

山东中医药大学第一临床医学院,山东 济南 250014山东大学齐鲁医院中医科,山东 济南 250012山东大学齐鲁医院中医科,山东 济南 250012

医药卫生

苦参碱癫痫网络毒理学神经毒性机器学习分子对接

MatrineEpilepsyNetwork toxicologyNeurotoxicityMachine learningMolecular docking

《药学研究》 2026 (7)

734-741,8

山东省自然科学基金项目(No.ZR2022QH163)齐鲁医派老年病中西汇通学术流派传承工作室项目(No.2022-93-1-10)

10.13506/j.cnki.jpr.2026.07.003

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