Background: Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear. Methods: Intraplanar injection of complete Freund’s adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells. Results: The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1β-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1β in mouse bone marrow-derived macrophages. Conclusion: Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro.
Neuroimmunomodulation

中文翻译：

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Nodakenetin 通过抑制 NF-κB 信号通路减轻炎症性疼痛超敏反应

背景：核因子 kappa-B (NF-κB) 信号通路介导的炎症性疼痛在过去十年中已成为一个越来越重要的临床问题。作为一种有效的抗氧化剂，Nodakenetin 已被证明对炎症具有显着的抑制作用。然而，Nodakenetin 对炎症性疼痛的治疗效果和潜在药理机制仍不清楚。方法：平面内注射完全弗氏佐剂 (CFA) 用于建立 C57BL/6 小鼠慢性炎症疼痛模型。慢性神经性疼痛模型通过坐骨神经结扎手术进行。进行 QRT-PCR 以估计肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β) 和白细胞介素-6 (IL-6) 的 RNA 水平。Western blot 用于证明 HEK293T 细胞中磷酸化 IkappaBα (IκBα)、p50 和 p65 的蛋白质水平。结果：中药羌活的生物活性成分主要有野达信素、异欧前胡素、孕烯醇酮。Nodakenetin 显着减轻了 CFA 引起的炎症性疼痛，但在小鼠模型中对手术引起的神经痛没有显着治疗作用。相反，异欧前胡素和孕烯醇酮不能缓解 CFA 引起的炎症性疼痛。从机制上讲，Nodakenetin 抑制 IL-1β 诱导的 NF-κB 通路激活和 HEK293T 细胞中 IκBα 的磷酸化。此外，Nodakenetin 治疗抑制了小鼠骨髓来源的巨噬细胞中 IL-6、TNF-α 和 IL-1β 的表达。结论： Nodakenetin 在体内减轻 CFA 注射诱导的炎症性疼痛，在体外调节 NF-κB 信号通路。
神经免疫调节