Oh Su-Yeon, Kim Yun-Ho, Kang Min-Kyung, Lee Eun-Jung, Kim Dong-Yeon, Oh Hyeongjoo, Kim Soo-Il, Na Woojin, Kang Il-Jun, Kang Young-Hee
Department of Food and Nutrition and Korean Institute of Nutrition, Hallym University, Chuncheon 24252, Korea.
Antioxidants (Basel). 2021 Mar 22;10(3):494. doi: 10.3390/antiox10030494.
Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs and blood streams, causing diverse respiratory diseases. Aesculetin, a coumarin derivative present in the Sancho tree and chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on PM-induced airway thickening and mucus hypersecretion is poorly understood. The current study examined whether naturally-occurring aesculetin inhibited airway thickening and mucus hypersecretion caused by urban PM (uPM, particles less than 10 μm). Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 μg/mL uPM for 8 weeks. To further explore the mechanism(s) involved in inhibition of uPM-induced mucus hypersecretion by aesculetin, bronchial epithelial BEAS-2B cells were treated with 1-20 µM aesculetin in the presence of 2 μg/mL uPM. Oral administration of aesculetin attenuated collagen accumulation and mucus hypersecretion in the small airways inflamed by uPM. In addition, aesculetin inhibited uPM-evoked inflammation and oxidant production in lung tissues. Further, aesculetin accompanied the inhibition of induction of bronchial epithelial toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EFGR) elevated by uPM. The inhibition of TLR4 and EGFR accompanied bronchial mucus hypersecretion in the presence of uPM. Oxidative stress was responsible for the epithelial induction of TLR4 and EGFR, which was disrupted by aesculetin. These results demonstrated that aesculetin ameliorated airway thickening and mucus hypersecretion by uPM inhalation by inhibiting pulmonary inflammation via oxidative stress-stimulated TLR4 and EGFR. Therefore, aesculetin may be a promising agent for treating airway mucosa-associated disorders elicited by urban coarse particulates.
颗粒物（PM）是悬浮在空气中的固体和液体空气污染物颗粒的混合物，其成分、大小和物理特征各不相同。由于PM能够深入肺部和血液循环，导致多种呼吸系统疾病，因此它是空气污染中最有害的形式。七叶亭是一种存在于独活树和菊苣中的香豆素衍生物，已知其在血管和免疫系统中具有抗氧化和抗炎作用。然而，其对PM诱导的气道增厚和黏液分泌过多的影响尚不清楚。本研究检测了天然存在的七叶亭是否能抑制城市PM（uPM，粒径小于10μm的颗粒）引起的气道增厚和黏液分泌过多。给小鼠口服10mg/kg七叶亭，并暴露于6μg/mL的uPM中8周。为了进一步探究七叶亭抑制uPM诱导的黏液分泌过多所涉及的机制，在存在2μg/mL uPM的情况下，用1-20μM七叶亭处理支气管上皮BEAS-2B细胞。口服七叶亭可减轻uPM引起的小气道炎症中胶原蛋白的积累和黏液分泌过多。此外，七叶亭可抑制uPM诱发的肺组织炎症和氧化剂生成。此外，七叶亭伴随着对uPM升高的支气管上皮Toll样受体4（TLR4）和表皮生长因子受体（EFGR）诱导的抑制。在存在uPM的情况下，TLR4和EGFR的抑制伴随着支气管黏液分泌过多。氧化应激是上皮细胞诱导TLR4和EGFR的原因，而七叶亭可破坏这种诱导。这些结果表明，七叶亭通过抑制氧化应激刺激的TLR4和EGFR引起的肺部炎症，改善了吸入uPM引起的气道增厚和黏液分泌过多。因此，七叶亭可能是治疗城市粗颗粒物引起气道黏膜相关疾病的一种有前景的药物。
