Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges. The airway resistance and dynamic compliance were recorded as the results of AHR. Bronchoalveolar lavage fluid (BALF) was collected and processed for differential cell counting. Hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were conducted to examine histopathological changes. The levels of asthma-related cytokines were measured by enzyme-linked immunosorbent assay. For in vitro analysis, the 16HBE cells were stimulated with 10 ng/mL transforming growth beta-1 (TGF-β1). Cell migration was estimated by Transwell assays and wound healing assays. E-cadherin, N-cadherin, and α-smooth muscle actin (α-SMA) were analyzed by western blotting, real-time quantitative polymerase chain reaction, immunofluorescence staining, and immunohistochemistry staining. The underlying mechanisms of the mitogen-activated protein kinase (MAPK) and Smad pathways were investigated by western blotting. In an ovalbumin-induced asthmatic mouse model, scutellarin suppressed inflammation and inflammatory cell infiltration into the lungs and attenuated AHR and airway remodeling. Additionally, scutellarin inhibited airway EMT (upregulated E-cadherin level and downregulated N-cadherin and α-SMA) in ovalbumin-challenged asthmatic mice. For in vitro analysis, scutellarin prevented the TGF-β1-induced migration and EMT in 16HBE cells. Mechanistically, scutellarin inhibits the phosphorylation of Smad2, Smad3, ERK, JNK, and p38 in vitro and in vivo. In conclusion, scutellarin can inactivate the Smad/MAPK pathways to suppress the TGF-β1-stimulated epithelial fibrosis and EMT and relieve airway inflammation and remodeling in asthma. This study provides a potential therapeutic strategy for asthma.

哮喘是一种慢性炎症性疾病，其特征是气道高反应性 (AHR)、炎症和重塑。上皮间质转化（EMT）是这些改变的重要参与者。灯盏乙素是从灯盏花中分离出来的。其血管松弛、心肌保护和抗炎作用已得到充分证实。本研究旨在检测灯盏乙素在哮喘中的生物学作用及其相关机制。类似哮喘的病症是由卵清蛋白激发引起的。记录气道阻力和动态顺应性作为AHR的结果。收集支气管肺泡灌洗液（BALF）并进行处理以进行分类细胞计数。进行苏木精和伊红染色、高碘酸希夫染色和Masson染色来检查组织病理学变化。通过酶联免疫吸附测定测定哮喘相关细胞因子的水平。对于体外分析，16HBE 细胞用 10 ng/mL 转化生长 beta-1 (TGF-β1) 刺激。通过 Transwell 测定和伤口愈合测定来估计细胞迁移。通过蛋白质印迹、实时定量聚合酶链反应、免疫荧光染色和免疫组织化学染色来分析 E-钙粘蛋白、N-钙粘蛋白和 α-平滑肌肌动蛋白 (α-SMA)。通过蛋白质印迹研究了丝裂原激活蛋白激酶 (MAPK) 和 Smad 通路的潜在机制。在卵清蛋白诱导的哮喘小鼠模型中，灯盏花乙素抑制炎症和炎症细胞浸润肺部，并减弱 AHR 和气道重塑。 此外，灯盏乙素可抑制卵清蛋白攻击的哮喘小鼠的气道 EMT（上调 E-钙粘蛋白水平并下调 N-钙粘蛋白和 α-SMA）。对于体外分析，灯盏乙素可阻止 16HBE 细胞中 TGF-β1 诱导的迁移和 EMT。从机制上讲，灯盏乙素在体外和体内抑制 Smad2、Smad3、ERK、JNK 和 p38 的磷酸化。总之，灯盏乙素可以灭活 Smad/MAPK 通路，抑制 TGF-β1 刺激的上皮纤维化和 EMT，缓解哮喘气道炎症和重塑。这项研究为哮喘提供了潜在的治疗策略。