姜黄素调控铁死亡干预帕金森病的网络药理学研究及实验验证  

Network pharmacological study and experimental verification of curcumin regulating ferroptosis in Parkinson's disease

作　　者：吴春阳 欧阳竞锋[1] WU Chunyang;OUYANG Jingfeng(Experimental Research Center of Chinese Academy of Medical Sciences,Beijing Key Research Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Major Diseases,Beijing 100700,China)

机构地区：[1]中国中医科学院医学实验中心,中医药防治重大疾病基础研究北京市重点实验室,北京100700

出　　处：《海南医科大学学报》2025年第5期360-372,共13页Journal of Hainan Medical University

基　　金：中国中医科学院科技创新工程资助项目(CI2021A00602)。

摘　　要：目的:基于网络药理学、分子对接及实验验证,探讨姜黄素(curcumin,Cur)调控铁死亡干预帕金森病(Parkinson's disease,PD)的可能靶标及作用机制。方法:通过Swiss Target Prediction、SEA等数据库获取Cur作用靶点。通过GeneCards数据库获取PD的治疗靶标。利用Venn在线工具获取共同作用靶点,通过Cytoscape插件获取核心靶点及核心子网络,并通过DAVID数据库进行富集分析及利用微生信平台进行可视化。通过FerrDb数据库获取铁死亡相关基因,并与Cur和PD的共同靶点进行综合探讨,对潜在治疗靶点作出预测。通过鱼藤酮构建C17.2 PD模型;CCK-8法确定Cur最佳浓度;试剂盒检测ROS、GSH、亚铁离子含量及GPx、SOD活性;RT-qPCR检测NFE2L2及NOX4基因表达情况,Western blot检测Nrf2、NOX4蛋白表达水平。结果:网络药理学预测得到NOX4、NFE2L2等17个Cur调控铁死亡抗帕金森病的可能作用靶标,并介导氧化应激相关信号通路调控铁死亡。体外实验验证,与模型组比较,2.0μmol/L Cur可降低ROS、亚铁离子含量(P<0.01),升高GSH含量(P<0.01)及GPx、SOD活性升高(P<0.05),抑制NOX4基因及蛋白表达(P<0.05)并促进Nrf2基因及蛋白表达(P<0.05)。结论:姜黄素可能通过调控Nrf2及NOX4改善鱼藤酮诱导的C17.2细胞的氧化应激及铁死亡状态,实现保护神经干细胞来改善PD的作用。Objective:To explore the potential targets and mechanisms by which curcumin regulates ferroptosis in the intervention of Parkinson's disease(PD)based on network pharmacology,molecular docking,and experimental validation.Methods:Curcumin targets were obtained using databases such as Swiss Target Prediction and SEA.Therapeutic targets for PD were sourced from the GeneCards database.Common targets were identified using Venn online tools,and core targets and networks were analyzed with Cytoscape plugins.Enrichment analysis was performed using the DAVID database,with visualization via microbioinformatics platforms.Ferroptosis-related genes were retrieved from the FerrDb database.An integrated analysis of common targets among curcumin,PD,and ferroptosis was conducted,predicting potential therapeutic targets.A C17.2 PD model was established using rotenone;the optimal concentration of curcumin was determined via CCK-8 assay.ROS,GSH,ferrous ion levels,and GPx and SOD activities were measured using kits,while RT-qPCR and Western blot analyses assessed NFE2L2 and NOX4 gene and protein expressions,respectively.Results:Network pharmacology identified 17 potential targets,including NOX4 and NFE2L2,through which curcumin may regulate ferroptosis in PD by mediating oxidative stress-related signaling pathways.In vi?tro experiments demonstrated that 2.0μmol/L curcumin significantly reduced ROS and ferrous ion levels(P<0.01),increased GSH content(P<0.01),and enhanced GPx and SOD activities(P<0.05),while inhibiting NOX4 gene and protein expression(P<0.05)and promoting Nrf2 gene and protein expression(P<0.05).Conclusion:Curcumin may improve oxidative stress and ferroptosis in rotenone-induced C17.2 cells by regulating Nrf2 and NOX4,thereby protecting neural stem cells and improving PD outcomes.

关 键 词：帕金森病 姜黄素 铁死亡 网络药理学 NRF2 NOX4 

分 类 号：R285[医药卫生—中药学]