The etiology of neuropathic pain is mostly caused by mechanical deformation and neuroinflammation, of which neuroinflammation is the main cause of chronic neuropathic pain. Activation of the TLR4/NF-κB signaling pathway mediates elevated levels of inflammatory cytokines, and we clearly demonstrated by in vivo and in vitro Western blot experiments that β-sitosterol significantly inhibited the elevated Toll-like receptor 4 (TLR4) expression levels and nuclear factor-kappa B (NF-κB) activation associated with inflammatory responses. In cellular experiments, we clearly saw that both β-sitosterol and TLR4/NF-κB signaling pathway inhibitors could inhibit M1 proinflammatory phenotype expression and promote M2 anti-inflammatory phenotype expression in GMI-R1 microglia by flow cytometry and immunofluorescence assays. Therefore, we suggest that β-sitosterol can affect microglial polarization by inhibiting the TLR4/NF-κB signaling pathway thereby reducing neuroinflammation and thus alleviating neuropathic pain.

Graphical Abstract

中文翻译：

---

β-谷甾醇通过抑制 TLR4/NF-κB 信号通路影响小胶质细胞极化来减轻神经性疼痛

神经病理性疼痛的病因多为机械变形和神经炎症所致，其中神经炎症是慢性神经病理性疼痛的主要原因。TLR4/NF-κB信号通路的激活介导炎症细胞因子水平升高，我们通过体内和体外Western blot实验清楚地证明，β-谷甾醇显着抑制Toll样受体4（TLR4）表达水平升高和核与炎症反应相关的因子-κB (NF-κB) 激活。在细胞实验中，我们通过流式细胞术和免疫荧光分析清楚地看到，β-谷甾醇和TLR4/NF-κB信号通路抑制剂均可抑制GMI-R1小胶质细胞中M1促炎表型表达并促进M2抗炎表型表达。因此，我们认为β-谷甾醇可以通过抑制TLR4/NF-κB信号通路影响小胶质细胞极化，从而减少神经炎症，从而减轻神经病理性疼痛。

图形概要