Xiao Bo, Zhou Guiming, Hou Lixia, Yang Lihong, Li Zhimei, Cai Yuchun, Zhao Ailing, Mo Biwen, Yao Dong
Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Guilin Medical University, 541199, Guilin, China; The Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China; Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China.
The Laboratory of Respiratory Disease, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China; Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Guilin Medical University, Guilin, 541000, China.
Pulm Pharmacol Ther. 2025 Sep;90:102380. doi: 10.1016/j.pupt.2025.102380. Epub 2025 Jul 29.
Icaritin, a bioactive phytomolecule derived from Epimedium flavonoids (EFs), has been shown to have anti-inflammatory, anti-proliferative, and pro-apoptotic properties. However, its potential mechanisms in asthma airway inflammation have not been elucidated. In this study, Ovalbumin (OVA)-induced asthma mouse model and human bronchial epithelial cells (BEAS-2B) were used to illustrate the effects and mechanisms of Icaritin on airway inflammation. Specific airway resistance (sRAW) was used to detect the airway hyperresponsiveness (AHR). Hematoxylin-eosin (H&E) and periodic acid schiff (PAS) were used to detect the pathological changes. Bronchoalveolar lavage fluid (BALF) was used to detect the airway inflammatory cells. Serum and supernatants were used to detect the cytokines. Immunohistochemistry (IHC) and western blotting were used to detect the expression of TLR4, p-65, p-p65, IκBα, and p-IκBα. Cell Counting Kit-8 (CCK-8) was used to detect the cell viability. Icaritin suppressed AHR, attenuated eosinophilic infiltration and mucus hypersecretion, and significantly reduced the levels of OVA-specific cytokines in asthmatic mice. Moreover, Icaritin inhibited TLR4 expression, decreased phosphorylation of IκBα, and reduced NF-κB p65 activation in lung tissue of asthmatic mice. Further mechanistic studies showed that Icaritin reduces TLR4-induced inflammatory factor expression and blocks TLR4-activated NF-κB pathway in BEAS-2B cells. These findings demonstrate for the first time that Icaritin suppresses airway inflammation in asthma by inhibiting the TLR4/NF-κB pathway, suggesting its potential as a therapeutic agent for asthma.
淫羊藿素是一种源自淫羊藿黄酮（EFs）的生物活性植物分子，已被证明具有抗炎、抗增殖和促凋亡特性。然而，其在哮喘气道炎症中的潜在机制尚未阐明。在本研究中，使用卵清蛋白（OVA）诱导的哮喘小鼠模型和人支气管上皮细胞（BEAS-2B）来说明淫羊藿素对气道炎症的影响和机制。使用特异性气道阻力（sRAW）检测气道高反应性（AHR）。苏木精-伊红（H&E）和过碘酸希夫（PAS）用于检测病理变化。支气管肺泡灌洗液（BALF）用于检测气道炎症细胞。血清和上清液用于检测细胞因子。免疫组织化学（IHC）和蛋白质印迹法用于检测TLR4、p-65、p-p65、IκBα和p-IκBα的表达。细胞计数试剂盒-8（CCK-8）用于检测细胞活力。淫羊藿素抑制哮喘小鼠的AHR，减轻嗜酸性粒细胞浸润和黏液分泌过多，并显著降低OVA特异性细胞因子水平。此外，淫羊藿素抑制哮喘小鼠肺组织中TLR4表达，降低IκBα磷酸化，并减少NF-κB p65激活。进一步的机制研究表明，淫羊藿素降低TLR4诱导的炎症因子表达，并阻断BEAS-2B细胞中TLR4激活的NF-κB途径。这些发现首次证明淫羊藿素通过抑制TLR4/NF-κB途径抑制哮喘气道炎症，表明其作为哮喘治疗药物的潜力。
