Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Laboratory for Marine Biological Products, Guangdong Provincial Center for Modern Agricultural Scientific Innovation, Shenzhen Institute of Guangdong Ocean University, Zhanjiang Municipal Key Laboratory of Marine Drugs and Nutrition for Brain Health, Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524088, China.
Mar Drugs. 2024 Jul 19;22(7):324. doi: 10.3390/md22070324.
Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, its potential effects on NDs remain unexplored. In LPS-induced BV-2 microglia, we found that Pol reduced the generation of NO and ROS and revealed inhibited expression of iNOS, COX-2, and inflammatory factors such as IL-6, TNF-α, and 1L-1β by Pol using qRT-PCR and Western blotting. These effects were found to be associated with the suppression of the NF-κB signaling pathway. Moreover, we evaluated the potential synergistic effects of aspergillusidone G (Asp G) when combined with Pol. Remarkably, co-treatment with low doses of Asp G enhanced the NO inhibition by Pol from approximately 30% to 80% in LPS-induced BV2 microglia, indicating a synergistic anti-inflammatory effect. A bioinformatics analysis suggested that the synergistic mechanism of Asp G and Pol might be attributed to several targets, including NFκB1, NRF2, ABL1, TLR4, and PPARα. These findings highlight the anti-neuroinflammatory properties of Pol and its enhanced efficacy when combined with Asp G, proposing a novel therapeutic strategy for managing neuroinflammation in NDs.
神经炎症是神经退行性疾病（NDs）进展的主要机制之一，小胶质细胞激活是神经炎症的主要特征。聚赖氨酸锌（Pol）是一种 L-肉碱和锌的螯合剂，广泛用作治疗胃溃疡的临床药物。然而，其在 NDs 中的潜在作用仍未得到探索。在 LPS 诱导的 BV-2 小胶质细胞中，我们发现 Pol 降低了 NO 和 ROS 的产生，并通过 qRT-PCR 和 Western blot 显示 Pol 抑制了 iNOS、COX-2 和炎症因子如 IL-6、TNF-α 和 1L-1β的表达。这些作用与 NF-κB 信号通路的抑制有关。此外，我们评估了曲古抑菌素 G（Asp G）与 Pol 联合使用的潜在协同作用。值得注意的是，低剂量的 Asp G 与 Pol 联合治疗可使 LPS 诱导的 BV2 小胶质细胞中 Pol 对 NO 的抑制作用从约 30%增强至 80%，表明具有协同抗炎作用。生物信息学分析表明，Asp G 和 Pol 的协同作用机制可能归因于几个靶点，包括 NFκB1、NRF2、ABL1、TLR4 和 PPARα。这些发现强调了 Pol 的抗神经炎症特性及其与 Asp G 联合使用时的增强功效，为管理 NDs 中的神经炎症提供了一种新的治疗策略。
