Falcarindiol通过Nrf2通路激活缓解哮喘的气道炎症和氧化应激
Falcarindiol alleviates airway inflammation and oxidative stress in asthma through Nrf2 pathway activation.
摘要(中文译文)
氧化应激和Th2型免疫反应在哮喘发病机制中发挥关键作用。法卡林二醇（FAD）是一种天然多炔类化合物，具有良好的抗炎和抗氧化特性，但其在哮喘治疗中的治疗机制和疗效仍有待探索。本研究采用卵清蛋白（OVA）诱导的小鼠哮喘模型和IL-13刺激的人支气管上皮细胞（BEAS-2B）来探究FAD的治疗机制。通过苏木精-伊红（H&E）染色、ELISA、流式细胞术和Western blotting综合评估气道炎症、氧化应激标志物及Nrf2通路激活情况。为建立机制因果关系，使用Nrf2抑制剂ML385和靶向shRNA敲低方法验证Nrf2激活在介导FAD保护效应中的关键作用。在OVA诱导的哮喘小鼠中，FAD（100或200 mg/kg）产生剂量依赖性治疗效果，显著降低炎症评分，减少气道壁和平滑肌厚度，大幅降低血清IgE水平，并减少支气管肺泡灌洗液（BALF）中的嗜酸性粒细胞浸润。此外，FAD有效改善氧化应激，同时抑制促炎细胞因子释放。在IL-13刺激的BEAS-2B细胞中，FAD剂量依赖性地保护细胞免于凋亡并恢复增殖能力，同时强烈激活Nrf2/HO-1/NQO1通路。机制验证研究表明，ML385介导的Nrf2抑制和Nrf2 shRNA敲低均在很大程度上消除了FAD的保护效应。FAD通过激活Nrf2通路发挥抗哮喘作用，有效减轻气道炎症、氧化应激和上皮损伤，使其成为哮喘治疗中一个有前景的候选药物。
Abstract
Oxidative stress and Th2-type immune responses play pivotal roles in asthma pathogenesis. Falcarindiol (FAD), a natural polyacetylene compound, exhibits promising anti-inflammatory and antioxidant properties, yet its therapeutic mechanism and efficacy in asthma treatment remain to be explored. An ovalbumin (OVA)-induced murine asthma model and IL-13-stimulated human bronchial epithelial cells (BEAS-2B) were employed to investigate FAD’s therapeutic mechanisms. Airway inflammation, oxidative stress markers, and Nrf2 pathway activation were comprehensively evaluated through hematoxylin and eosin (H&E) staining, ELISA, flow cytometry, and Western blotting. To establish mechanistic causality, the Nrf2 inhibitor ML385 and targeted shRNA knockdown approaches were used to validate the essential role of Nrf2 activation in mediating FAD’s protective effects. In OVA-induced asthmatic mice, FAD (100 or 200 mg/kg) produced dose-dependent therapeutic benefits, significantly reducing inflammatory scores, decreasing airway wall and smooth muscle thickness, substantially lowering serum IgE levels, and diminishing eosinophil infiltration in bronchoalveolar lavage fluid (BALF). Additionally, FAD effectively ameliorated oxidative stress, while simultaneously suppressing pro-inflammatory cytokine release. In IL-13-stimulated BEAS-2B cells, FAD dose-dependently protected against apoptosis and restored proliferation capacity while robustly activating the Nrf2/HO-1/NQO1 pathway. Mechanistic validation studies revealed that both ML385-mediated Nrf2 inhibition and Nrf2 shRNA knockdown largely abrogated FAD’s protective effects. FAD exerts anti-asthmatic effects through Nrf2 pathway activation, effectively mitigating airway inflammation, oxidative stress, and epithelial injury, establishing it as a promising therapeutic candidate for asthma.
如何引用
AMA
Xiuhua Jiang, Shengxiu Lai, Zhen Lin, Fuhuang Lai, Huifang Wu. Falcarindiol alleviates airway inflammation and oxidative stress in asthma through Nrf2 pathway activation.. Scientific reports. 2026; doi:10.1038/s41598-026-37962-5.
APA
Xiuhua Jiang, Shengxiu Lai, Zhen Lin, Fuhuang Lai, Huifang Wu (2026). Falcarindiol alleviates airway inflammation and oxidative stress in asthma through Nrf2 pathway activation.. Scientific reports. https://doi.org/10.1038/s41598-026-37962-5
GB/T 7714
Xiuhua Jiang, Shengxiu Lai, Zhen Lin, Fuhuang Lai, Huifang Wu. Falcarindiol alleviates airway inflammation and oxidative stress in asthma through Nrf2 pathway activation.[J]. Scientific reports, 2026 doi:10.1038/s41598-026-37962-5.
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