Nigdelioglu Dolanbay Serap, Şirin Seda, Aslim Belma
Faculty of Science, Department of Biology, Gazi University, 06500, Teknikokullar, Ankara, Turkey.
Mol Neurobiol. 2025 Mar;62(3):3833-3847. doi: 10.1007/s12035-024-04520-x. Epub 2024 Sep 27.
Studies in the existing literature propose that allocryptopine possesses both antioxidant and anti-inflammatory properties, showcasing its neuroprotective effects by potentially mitigating oxidative stress and inflammation. This study aims to investigate the antioxidant and anti-inflammatory effects of allocryptopine on various targets and potential mechanisms that have not been previously explored in the literature. Initially, we used MTT and LDH methods to evaluate the effects of allocryptopine on cell viability in BV-2 cells exposed to LPS-induced damage. Subsequently, we evaluated the impact of allocryptopine on pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), other inflammatory mediators (Cox-2 and iNOS), and p38 MAPK genes and proteins through qRT-PCR and Western blot analyses. Also, we evaluated the impact of allocryptopine on NF-κB proteins (TLR4, MyD88, IκBα, p-p50, and p-p65) through ELISA assay. Molecular docking analyses were performed to investigate the potential binding of allocryptopine to target proteins (TLR4, MyD88, IκBα, p50, p65, MKK3, MKK4, MKK6, p38, AP-1 (c-Jun and ATF2), IL-1β, IL-6, TNF-α, Cox-2, and iNOS) associated with the TLR4, NF-κB, and p38 MAPK pathways. Our results indicate that allocryptopine exerts a comprehensive influence on pro-inflammatory cytokines and other inflammatory mediators by inhibiting TLR4 signaling and modulating the NF-κB and p38 MAPK pathways. The outcomes of our study suggest that the antioxidant and anti-inflammatory efficacy of allocryptopine is intricately linked to the modulation of key molecular pathways associated with oxidative stress and inflammation. These findings highlight the potential of allocryptopine as a therapeutic agent for addressing neurodegenerative diseases by safeguarding neuronal health.
现有文献中的研究表明，别隐品碱具有抗氧化和抗炎特性，通过潜在地减轻氧化应激和炎症来展现其神经保护作用。本研究旨在探讨别隐品碱对各种靶点的抗氧化和抗炎作用以及文献中尚未探讨过的潜在机制。首先，我们使用MTT和LDH方法评估别隐品碱对暴露于LPS诱导损伤的BV-2细胞活力的影响。随后，我们通过qRT-PCR和蛋白质印迹分析评估别隐品碱对促炎细胞因子（IL-1β、IL-6和TNF-α）、其他炎症介质（Cox-2和iNOS）以及p38 MAPK基因和蛋白质的影响。此外，我们通过ELISA测定评估别隐品碱对NF-κB蛋白质（TLR4、MyD88、IκBα、p-p50和p-p65）的影响。进行分子对接分析以研究别隐品碱与与TLR4、NF-κB和p38 MAPK途径相关的靶蛋白（TLR4、MyD88、IκBα、p50、p65、MKK3、MKK4、MKK6、p38、AP-1（c-Jun和ATF2）、IL-1β、IL-6、TNF-α、Cox-2和iNOS）的潜在结合。我们的结果表明，别隐品碱通过抑制TLR4信号传导和调节NF-κB和p38 MAPK途径对促炎细胞因子和其他炎症介质产生全面影响。我们的研究结果表明，别隐品碱的抗氧化和抗炎功效与氧化应激和炎症相关关键分子途径的调节密切相关。这些发现凸显了别隐品碱作为一种通过保护神经元健康来治疗神经退行性疾病的治疗剂的潜力。
