Nootkatone (NKT) exhibits potential pharmacological activities including anti-oxidation and anti-inflammation. Nevertheless, little is known about the roles of NKT in asthmatic airway inflammation. In the study, mice were sensitized and challenged with ovalbumin (OVA) to establish experimental allergic asthma model. After treatment with NKT, lung tissues, peripheral blood, and bronchoalveolar lavage fluid (BALF) were collected to assess inflammatory cytokines, oxidative stress, and pathological alternations. The effects of NKT on regulating reactive oxygen species (ROS)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation was assessed in IL-13-treated BEAS-2B cell model. We found that NKT treatment decreased the production of Th2 inflammatory cytokines (IL-4, IL-5, and IL-13) in BALF and IgE levels in serum, and alleviated inflammatory cell penetration, goblet cell proliferation, collagen accumulation, and mucus hypersecretion in lung tissues. NKT treatment mitigated oxidative stress and NLRP3 inflammasome activation in asthmatic mice. IL-13 treatment induced oxidative stress and NLRP3-mediated pyroptosis in BEAS-2B bronchial epithelial cells, whereas these effects were blocked by NKT. NKT protected against airway remodeling, as indicated by decreased epithelial-mesenchymal transition. Taken together, these results demonstrate that NKT mitigates asthmatic airway inflammation by inhibiting ROS-triggered NLRP3 activation and may be a potential agent for treating asthma.

中文翻译：

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Nootkatone 通过抑制 ROS 诱导的 NLRP3 炎症小体激活来减轻哮喘小鼠的气道炎症。

Nootkatone (NKT) 具有潜在的药理活性，包括抗氧化和抗炎。然而，人们对 NKT 在哮喘气道炎症中的作用知之甚少。在该研究中，用卵清蛋白（OVA）对小鼠进行致敏和激发，建立实验性过敏性哮喘模型。NKT治疗后，收集肺组织、外周血和支气管肺泡灌洗液（BALF）以评估炎症细胞因子、氧化应激和病理改变。在 IL-13 处理的 BEAS-2B 细胞模型中评估 NKT 对调节活性氧 (ROS) 诱导的 NLR 家族热蛋白结构域 3 (NLRP3) 炎性体激活的影响。我们发现 NKT 治疗降低了 BALF 中 Th2 炎症细胞因子（IL-4、IL-5 和 IL-13）的产生以及血清中 IgE 的水平，并减轻了炎症细胞渗透、杯状细胞增殖、胶原蛋白积累和粘液分泌过多在肺组织中。NKT 治疗减轻了哮喘小鼠的氧化应激和 NLRP3 炎性体激活。IL-13 治疗可诱导 BEAS-2B 支气管上皮细胞氧化应激和 NLRP3 介导的细胞焦亡，而这些作用可被 NKT 阻断。上皮-间质转化减少表明 NKT 可以防止气道重塑。综上所述，这些结果表明 NKT 通过抑制 ROS 触发的 NLRP3 激活来减轻哮喘气道炎症，并且可能是治疗哮喘的潜在药物。