秋水仙碱治疗神经损伤的网络药理学研究

Network Pharmacology Study of Colchicine in the Treatment of Neurological Injury

摘要

目的 运用网络药理学和分子对接技术,探讨秋水仙碱在调控铁死亡治疗神经损伤中的作用。方法 使用PubChem和Swiss Target Prediction数据库获得秋水仙碱靶点,GeneCards、OMIM和DisGeNET数据库获得神经损伤靶点,FerrDb数据库获得铁死亡靶点,利用Venny 2.1.0工具获得三者交集靶点。基于STRING数据库构建PPI网络,并用Metascape进行GO和KEGG通路富集分析。最后,使用Autodock Vina对秋水仙碱与前十靶点进行分子对接分析。结果 秋水仙碱靶点401个,神经损伤靶点3 367个,铁死亡靶点1 543个,交集靶点57个。PPI网络显示TP53、IL6、EGFR等为主要靶点,KEGG分析表明秋水仙碱通过Wnt信号通路调控铁死亡治疗神经损伤。分子对接结果显示秋水仙碱与多个靶点结合良好。结论 秋水仙碱可能通过Wnt信号通路调控相关基因,治疗神经损伤。

Abstract

Objective This study utilizes network pharmacology and molecular docking techniques to explore the role of colchicine in regulating ferroptosis for the treatment of neurological injury. Methods Colchicine targets were obtained from the PubChem and Swiss Target Prediction databases, while targets related to neurological injury were retrieved from the GeneCards, OMIM, and DisGeNET databases. Ferroptosis targets were sourced from the FerrDb database, and the Venny 2.1.0 tool was accustomed to identify the intersection of these three sets. A protein-protein interaction (PPI) network was constructed based on the STRING database, and GO and KEGG pathway enrichment analyses were conducted using Metascape. Ultimately, molecular docking analyses of colchicine with the top ten targets were performed using Autodock Vina. Results There were 401 targets for colchicine, 3 367 for neurological injury, and 1 543 for ferroptosis, with 57 intersection targets. The PPI network identified TP53, IL6, EGFR, and others as major targets. KEGG analysis indicated that colchicine regulated ferroptosis through the Wnt signaling pathway to treat neurological injury. Molecular docking results showed that colchicine bound well to multiple targets. Conclusion Colchicine may regulate related genes through the Wnt signaling pathway to treat neurological injury.

关键词

秋水仙碱 / 铁死亡 / 神经损伤 / 网络药理学 / 分子对接

Key words

colchicine / ferroptosis / neurological injury / network pharmacology / molecular docking

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基金资助

国家自然科学基金（82204929）; 安徽高校协同创新项目（GXXT-2023-073）