Park Sin-Hye, Sim Young Eun, Oh Su Yeon, Kang Min-Kyung, Kang Il-Jun, Kang Young-Hee
Department of Food Science and Nutrition and Korean Institute of Nutrition, Hallym University, Hallymdaehakgil 1, Chuncheon 24252, Republic of Korea.
Department of Food Science and Nutrition, Andong National University, Gyeongdong-ro 1375, Andong 36729, Republic of Korea.
ACS Omega. 2025 May 15;10(20):20866-20874. doi: 10.1021/acsomega.5c02198. eCollection 2025 May 27.
Particulate matter (PM) is a mixture of solid and liquid air pollutants floating in the air, and it is the most harmful form of air pollutant because it can penetrate deep into the lungs and bloodstream and cause various breathing problems. Neutrophil elastase (NE) is known to be a major constituent of lung proteolytic activity and potently stimulates mucus secretion during airway inflammation. Aesculetin is a coumarin derivative that has anti-inflammatory properties in blood vessels and the immune system. This study investigated whether aesculetin inhibited bronchial barrier destruction caused by urban PM10 (uPM10, particles less than 10 μm). Balb/c mice were orally administrated with 10 mg/kg aesculetin while inhaling 6 μg/mL of uPM10 for 8 weeks. In addition, human bronchial epithelial BEAS-2B cells were exposed to 2 μg/mL uPM10 or 0.5 μg/mL NE in the presence of 1-20 μM aesculetin. Oral administration of aesculetin attenuated neutrophil infiltration and accumulation in the small airways inflamed by uPM10 and suppressed NE-mediated neutrophil inflammation in the airways. The supplementation of aesculetin boosted bronchial levels of junction proteins of occludin-1 and ZO-1, depleted due to uPM10 inhalation, indicating that this compound blocked airway epithelial barrier disruption caused by uPM10. Consistently, aesculetin enhanced the induction of occludin-1 and ZO-1 in BEAS-2B cells exposed to either uPM10 or NE. On the other hand, aesculetin suppressed bronchial matrix metalloproteinase (MMP)-2 in uPM10-loaded mice. Moreover, aesculetin inhibited the bronchial induction of protease-activated receptor (PAR)-2. Collectively, aesculetin improved the upper airways damaged by the inhalation of urban coarse PM through inhibiting NE-driven neutrophil inflammation and MMP-2 activation involving PAR-2. Therefore, anti-inflammatory aesculetin may be a promising natural agent to strengthen the airway epithelial barrier disrupted by activation of PAR-2-NE and PAR-2-MMP-2 in dusty urban environments.
颗粒物（PM）是悬浮在空气中的固体和液体空气污染物的混合物，它是最有害的空气污染物形式，因为它可以深入肺部和血液，导致各种呼吸问题。中性粒细胞弹性蛋白酶（NE）是肺蛋白水解活性的主要成分，在气道炎症期间能有效刺激黏液分泌。七叶亭是一种香豆素衍生物，在血管和免疫系统中具有抗炎特性。本研究调查了七叶亭是否能抑制城市PM10（uPM10，直径小于10μm的颗粒）引起的支气管屏障破坏。给Balb/c小鼠口服10mg/kg七叶亭，同时吸入6μg/mL的uPM10，持续8周。此外，在存在1-20μM七叶亭的情况下，将人支气管上皮BEAS-2B细胞暴露于2μg/mL uPM10或0.5μg/mL NE中。口服七叶亭可减轻uPM10引发的小气道中性粒细胞浸润和聚集，并抑制气道中NE介导的中性粒细胞炎症。补充七叶亭可提高因吸入uPM10而减少的紧密连接蛋白occludin-1和ZO-1的支气管水平，表明该化合物可阻止uPM10引起的气道上皮屏障破坏。同样，七叶亭增强了暴露于uPM10或NE的BEAS-2B细胞中occludin-1和ZO-1的诱导。另一方面，七叶亭抑制了uPM10负荷小鼠的支气管基质金属蛋白酶（MMP）-2。此外，七叶亭抑制了支气管中蛋白酶激活受体（PAR）-2的诱导。总体而言，七叶亭通过抑制NE驱动的中性粒细胞炎症以及涉及PAR-2的MMP-2激活，改善了因吸入城市粗颗粒物而受损的上呼吸道。因此，具有抗炎作用的七叶亭可能是一种有前景的天然药物，可加强在多尘城市环境中因PAR-2-NE和PAR-2-MMP-2激活而破坏的气道上皮屏障。
