Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200433, China.
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200433, China.
Int Immunopharmacol. 2021 May;94:107460. doi: 10.1016/j.intimp.2021.107460. Epub 2021 Feb 20.
Allergic asthma is a common chronic inflammatory disease characterized by airway inflammation, mucus hypersecretion and airway remodeling. Autophagy is a highly conserved intracellular degradation pathway in eukaryotic cells. There is growing evidence suggesting that dysregulation of autophagy is involved in the pathological process of asthma. Luteolin is a typical flavonoid compound with anti-inflammatory, anti-allergic and immune-enhancing functions. Previous studies have shown that luteolin can attenuate airway inflammation and hypersensitivity in asthma. However, whether luteolin can play a role in treating asthma by regulating autophagy remains unclear. The aim of the present study was to evaluate the therapeutic effect of luteolin on ovalbumin (OVA)-induced asthmatic mice, observe its effect on the level of autophagy in lung tissues, and further elucidate its underlying mechanism. The results showed that OVA-induced mice developed airway hyperresponsiveness, mucus over-production and collagen deposition. The number of inflammatory cells, levels of interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and OVA-specific IgE in serum were significantly increased. Furthermore, the infiltration of inflammatory cells was observed along with the activation of autophagy in lung tissues. Luteolin treatment significantly inhibited the OVA-induced inflammatory responses and the level of autophagy in lung tissues as well. Moreover, luteolin activated the PI3K/Akt/mTOR pathway and inhibited the Beclin-1-PI3KC3 protein complex in lung tissues of asthmatic mice. In conclusion, this study explored the regulatory mechanism of luteolin on autophagy in allergic asthma, providing biologic evidence for its clinical application.
变应性哮喘是一种常见的慢性炎症性疾病，其特征为气道炎症、黏液高分泌和气道重塑。自噬是真核细胞中高度保守的细胞内降解途径。越来越多的证据表明，自噬失调参与了哮喘的病理过程。木樨草素是一种具有抗炎、抗过敏和免疫增强功能的典型类黄酮化合物。先前的研究表明，木樨草素可以减轻哮喘中的气道炎症和过敏反应。然而，木樨草素是否可以通过调节自噬来发挥治疗哮喘的作用尚不清楚。本研究旨在评估木樨草素对卵清蛋白（OVA）诱导的哮喘小鼠的治疗作用，观察其对肺组织自噬水平的影响，并进一步阐明其潜在机制。结果显示，OVA 诱导的小鼠出现气道高反应性、黏液过度产生和胶原沉积。支气管肺泡灌洗液（BALF）中炎症细胞数量、白细胞介素（IL）-4、IL-5 和 IL-13 水平以及血清中 OVA 特异性 IgE 均显著增加。此外，还观察到肺组织中炎症细胞浸润和自噬激活。木樨草素治疗显著抑制了 OVA 诱导的炎症反应和肺组织中的自噬水平。此外，木樨草素激活了 PI3K/Akt/mTOR 通路，并抑制了哮喘小鼠肺组织中的 Beclin-1-PI3KC3 蛋白复合物。综上所述，本研究探讨了木樨草素对变应性哮喘中自噬的调节机制，为其临床应用提供了生物学依据。
