小胶质细胞的异常激活和促炎细胞因子的产生可导致慢性神经炎症，这是帕金森病（PD）的重要病理特征。莲心碱是一种从莲子中提取的化合物，此前有报道称其对多种癌症、心肌损伤和缺氧缺血性脑病的发展具有保护作用。然而，它对神经炎症中小胶质细胞功能的影响仍有待阐明。本研究使用网络药理学和脂多糖 (LPS) 模型筛选来证明莲心碱可抑制 LPS 处理的 BV-2 细胞中诱导型一氧化氮合酶、白细胞介素 6 和肿瘤坏死因子 α 的产生。莲心碱的工作浓度对 BV-2 细胞没有产生细胞毒性作用。从机制上讲，莲心碱通过抑制 NF-κB p65 亚基的磷酸化和核转位来减轻炎症。在体内，甲基莲心碱可以保护小鼠免受黑质炎症反应，并抑制 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的 PD 模型中神经紊乱的发展。本研究表明莲心碱通过抑制 NF-κB 信号传导来抑制 LPS 介导的小胶质细胞激活。这些发现可能为PD的预防和未来治疗提供新的参考。

Abnormal activation of microglia and the production of proinflammatory cytokines can lead to chronic neuroinflammation, which is an important pathological characteristic of Parkinson's disease (PD). Neferine is a chemical compound extracted from lotus seed which has previously been reported to exert protective effects on the development of several types of cancer, myocardial injury and hypoxic‑ischemic encephalopathy. However, its effect on microglial functions in neuroinflammation remains to be clarified. The present study used network pharmacology and screening in a lipopolysaccharide (LPS) model to demonstrate that neferine suppresses the production of inducible nitric oxide synthase, interleukin‑6 and tumor necrosis factor α in LPS‑treated BV‑2 cells. The working concentration of neferine did not exert cytotoxic effects on BV‑2 cells. Mechanistically, neferine attenuated inflammation by inhibiting the phosphorylation and nuclear translocation of the NF‑κB p65 subunit. In vivo, neferine protected mice from the inflammatory response in the substantia nigra and inhibited the development of nervous disorders in the 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine‑induced PD model. The present study demonstrated that neferine inhibited LPS‑mediated activation of microglia by inhibiting NF‑κB signaling. These findings may provide a new reference for the prevention and future treatment of PD.