Sodium houttuyfonate (SH) is a chemical compound synthesized by houttuynin and sodium bisulfite. As it has antinflammatory effects, SH has been widely used to treat autoimmune diseases, including post events following traumatic brain injury (TBI). Meanwhile, NOD-like receptor with pyrin domain containing-3 (NLRP3) inflammasomes in microglia may play a central role in TBI. But to date, the intracellular mechanisms involved in the anti-inflammatory effects of SH in TBI remain unknown, especially whether regulating NLRP3. To gain an insight into this possibility, we conducted cell culture and biochemical studies on the effect of SH on NLRP3 inflammasome in microglia. The results showed that SH inhibited TLR4 and NLRP3 inflammasome activation in the microglia cell. In parallel, phosphorylation of ERK and NF-κB p65, which play a key role in NLRP3 inflammasome formation, was decreased. Intraperitoneal injection of SH into TBI mice significantly reduced the modified neurological severity score (mNSS), as well as the degree of microglia apoptosis post-controlled cortical impact (CCI). Immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction (RT-PCR) revealed that SH markedly reduced NLRP3 inflammasome activation, TLR4 activity, phosphorylation of ERK and NF-κB. Moreover, SH significantly inhibited microglia activation post-CCI, but effectively promoted the astrocyte activation and angiopoiesis. Taken together, our research provides evidence that SH attenuated neurological deficits post TBI through inhibiting NLRP3 inflammasome activation, via influencing the TLR4/NF-κB signaling pathway. These findings explain the intracellular mechanism of the anti-inflammatory activity caused by SH treatment following TBI.

中文翻译：

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鱼腥草酸钠通过抑制 NLRP3 炎症小体减轻小鼠脑外伤后的神经缺陷

鱼腥草酸钠 (SH) 是由鱼腥草素和亚硫酸氢钠合成的化合物。由于它具有抗炎作用，SH 已被广泛用于治疗自身免疫性疾病，包括创伤性脑损伤 (TBI) 后的事后事件。同时，小胶质细胞中含有 pyrin domain-3 (NLRP3) 炎性体的 NOD 样受体可能在 TBI 中起核心作用。但迄今为止，涉及 SH 在 TBI 中的抗炎作用的细胞内机制仍然未知，尤其是是否调节 NLRP3。为了深入了解这种可能性，我们对 SH 对小胶质细胞中 NLRP3 炎性体的影响进行了细胞培养和生化研究。结果表明，SH抑制小胶质细胞中TLR4和NLRP3炎症小体的活化。同时，ERK 和 NF-κB p65 的磷酸化，在 NLRP3 炎性体形成中起关键作用的 NLRP3 减少。向 TBI 小鼠腹腔注射 SH 显着降低了改良的神经严重程度评分 (mNSS)，以及小胶质细胞凋亡后控制皮质影响 (CCI) 的程度。免疫组织化学、蛋白质印迹分析和逆转录聚合酶链反应 (RT-PCR) 显示，SH 显着降低了 NLRP3 炎性体激活、TLR4 活性、ERK 和 NF-κB 的磷酸化。此外，SH 显着抑制 CCI 后小胶质细胞的活化，但有效促进星形胶质细胞的活化和血管生成。总之，我们的研究提供了证据，表明 SH 通过影响 TLR4/NF-κB 信号通路抑制 NLRP3 炎性体激活，从而减轻了 TBI 后的神经功能缺损。