未成熟的瑞士悬钩子（uRO）含有多种具有有益生理活性的天然多酚化合物，尤其富含鞣花酸（EA）。EA在嗜酸性哮喘动物模型中改善了2型炎症和气道过度反应。EA通过肠道微生物代谢生成尿石素A（UA），具有抗炎性质。然而，目前尚不清楚uRO、EA和UA是否能减轻呼吸道上皮细胞和中性粒细胞的炎症反应和氧化应激。本研究将炎症引发于A549（人肺上皮细胞）和dHL-60细胞（人前髓细胞白血病HL-60细胞分化得到的类中性粒细胞），并用不同浓度的uRO水提取物（uRO-w）、EA和UA进行处理。EA、uRO-w和UA抑制了IL-1β刺激下A549细胞中炎性细胞因子和趋化因子水平的表达，减少了基质金属蛋白酶-9的表达。通过分析这些炎症分子表达的机制，发现EA、uRO-w和UA调节了糖皮质激素敏感的丝裂原活化蛋白激酶、核因子κB和糖皮质激素不敏感的AKT。此外，uRO-w、EA和UA显著降低了花生四烯酸酯12-十四酸酯刺激下的dHL-60细胞中活性氧水平，并抑制了中性粒细胞外囊形成。因此，我们的结果表明uRO-w、EA和UA是预防和治疗炎症性呼吸道疾病的潜在治疗药物。

Unripe Rubus occidentalis (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2 inflammation and airway hyperresponsiveness in animal models of eosinophilic asthma. EA is metabolized by the gut microbiota to urolithin A (UA), which exhibits anti-inflammatory properties. However, it remains unclear whether uRO, EA, and UA reduce inflammatory responses and oxidative stress in respiratory epithelial cells and neutrophils. In this study, inflammation was induced in A549 (human lung epithelial cells) and dHL-60 cells (neutrophil-like cells differentiated from human promyelocytic leukemia HL-60 cells) and treated with various concentrations of water extract of uRO (uRO-w), EA, and UA. EA, uRO-w and UA suppressed the inflammatory cytokine and chemokine levels and reduced the expression of matrix metalloproteinase-9 in A549 cells stimulated with IL-1β. As a result of analyzing the mechanism by which these inflammatory molecules are expressed, it was found that EA, uRO-w, and UA regulated corticosteroid-sensitive mitogen activated protein kinase, nuclear factor κB, and corticosteroid-insensitive AKT. In addition, uRO-w, EA, and UA significantly reduced reactive oxygen species levels in phorbol 12-myristate 13-acetate-stimulated dHL-60 cells and inhibited neutrophil extracellular trap formation. Therefore, our results suggest that uRO-w, EA, and UA are potential therapeutic agents for preventing and treating inflammatory respiratory diseases.