Affiliated Hospital of Nanjing University of Chinese Medicine/ Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, Jiangsu Province, China.
School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117203. doi: 10.1016/j.jep.2023.117203. Epub 2023 Sep 19.
Excessive secretion of airway mucus may be an important pathological factor of air pollution-induced acute asthma attacks. Treatment of airway mucus hypersecretion improves asthma aggravated by air pollutants. Qufeng Xuanbi Formula (QFXBF) has been used to treat asthma for more than 30 years. However, whether QFXBF inhibits asthmatic mucus secretion exacerbated by air pollutants has not yet been established.
This study aimed to evaluate the effect of QFXBF on airway mucus secretion and the mechanism of action in an air pollutant benzo[a]pyrene (BaP)-induced mouse model of aggravated asthma.
Ovalbumin (OVA) and BaP co-exposure were used to establish the aggravated asthma model. The average enhanced pause (Penh), serum OVA-specific IgE, and changes in lung histopathology were determined. 16HBE cells exposed to BaP, treatment with QFXBF, arylhydrocarbon receptor (AhR) signal antagonist SR1, reactive oxygen species (ROS) antagonist NAC, or extracellular signal-regulated kinase (ERK1/2) signal antagonist U0126 were established to investigate the effect of QFXBF on BaP-induced mucus secretion and its target. The mRNA and protein expression levels of MUC5AC in the lung tissue and 16HBE cells were examined. We also studied the effect of QFXBF on ROS production. Finally, the protein expression of AhR, phospho-extracellular signal-regulated kinases (p-ERK1/2), and ERK1/2 in 16HBE cells and lung tissues was determined by western blotting.
Administration of QFXBF significantly alleviated the pathological symptoms, including Penh, serum OVA-specific IgE, and changes in lung histopathology in a BaP-induced mouse model of aggravated asthma. QFXBF inhibited MUC5AC expression in asthmatic mice and 16HBE cells exposed to BaP. ROS production, AhR expression, and ERK1/2 phosphorylation were significantly increased in BaP-induced asthmatic mice and 16HBE cells. Signaling pathway inhibitors StemRegenin 1 (SR1), NAC, and U0126 significantly inhibitedBaP-induced MUC5AC expression in 16HBE cells. SR1 reversed Bap-induced ROS production and ERK activation, and NAC inhibited Bap-induced ERK activation. In addition, QFXBF regulated AhR signaling, inhibited ROS production, reversed ERK activation, and downregulated mucus secretion to improve asthma aggravated by air pollutant BaP.
QFXBF can ameliorate mucus secretion in BaP-induced aggravated asthmatic mice and 16HBE cells, and the specific mechanism may be related to the inhibition of the AhR/ROS/ERK signaling pathway.
气道黏液过度分泌可能是空气污染诱发急性哮喘发作的一个重要病理因素。治疗气道黏液高分泌可改善污染物诱发的哮喘加重。祛风宣痹方（QFXBF）已用于治疗哮喘 30 多年。然而，QFXBF 是否抑制空气污染诱发的哮喘黏液分泌增加尚未确定。
本研究旨在评估 QFXBF 对污染物苯并[a]芘（BaP）诱导的哮喘加重模型中气道黏液分泌的作用及其作用机制。
采用卵清蛋白（OVA）和 BaP 共同暴露建立哮喘加重模型。测定平均呼气暂停（Penh）、血清 OVA 特异性 IgE 以及肺组织病理学变化。建立 BaP 暴露、QFXBF 处理、芳烃受体（AhR）信号拮抗剂 SR1、活性氧（ROS）拮抗剂 NAC、细胞外信号调节激酶（ERK1/2）信号拮抗剂 U0126 处理的 16HBE 细胞，以研究 QFXBF 对 BaP 诱导的黏液分泌及其靶点的影响。检测肺组织和 16HBE 细胞中 MUC5AC 的 mRNA 和蛋白表达水平。还研究了 QFXBF 对 ROS 生成的影响。最后，通过 Western blot 法测定 16HBE 细胞和肺组织中 AhR、磷酸化细胞外信号调节激酶（p-ERK1/2）和 ERK1/2 的蛋白表达。
QFXBF 给药可显著减轻 BaP 诱导的小鼠哮喘加重模型中的病理症状，包括 Penh、血清 OVA 特异性 IgE 和肺组织病理学变化。QFXBF 抑制哮喘小鼠和 BaP 暴露的 16HBE 细胞中 MUC5AC 的表达。BaP 诱导的哮喘小鼠和 16HBE 细胞中 ROS 产生、AhR 表达和 ERK1/2 磷酸化明显增加。信号通路抑制剂 StemRegenin 1（SR1）、NAC 和 U0126 显著抑制 16HBE 细胞中 BaP 诱导的 MUC5AC 表达。SR1 逆转了 BaP 诱导的 ROS 产生和 ERK 激活，而 NAC 抑制了 BaP 诱导的 ERK 激活。此外，QFXBF 调节 AhR 信号，抑制 ROS 产生，逆转 ERK 激活，并下调黏液分泌，从而改善由空气污染物 BaP 引起的哮喘加重。
QFXBF 可改善 BaP 诱导的哮喘加重小鼠和 16HBE 细胞中的黏液分泌，其具体机制可能与抑制 AhR/ROS/ERK 信号通路有关。
