Li Zhihua, Yan Mingrui, Bi Jiaqi, Mo Biwen
College of Pharmacy, Guilin Medical University, Guilin 541199, Guangxi, People's Republic of China.
Postdoctoral Innovation Practice Base, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, Guangxi, People's Republic of China.
APL Bioeng. 2025 Jul 18;9(3):036105. doi: 10.1063/5.0251258. eCollection 2025 Sep.
Asthma is a prevalent chronic respiratory condition characterized by airway remodeling, which contributes to irreversible airway narrowing and impaired lung function. Current therapies fail to effectively address this structural alteration. This study introduces an innovative strategy combining Quercetin, a natural flavonoid with anti-inflammatory and anti-proliferative properties, and chitosan-alginate nanoparticles (CA-NPs) to enhance bioavailability and therapeutic efficacy. By activating the Hippo signaling pathway, CA-NPs-Quercetin inhibits the proliferation and migration of human airway smooth muscle cells (HASMCs), key drivers of airway remodeling. experiments demonstrated significant suppression of HASMC proliferation and migration, with increased apoptosis rates attributed to the phosphorylation of YAP and TAZ, which restricted their nuclear translocation. experiments showed that CA-NPs-Quercetin significantly improved airway inflammation in asthmatic mice, reducing the total number of inflammatory cells and eosinophils in the bronchoalveolar lavage fluid, with a significant reduction in IL-4 expression (56.65%) and significant upregulation of IL-10 (130.91%) and IFN-γ (156.58%) levels. Moreover, CA-NPs-Quercetin reduced collagen deposition in lung tissue (Quercetin group reduced by 42.53% and CA-NPs-Quercetin group reduced by 73.20%) and improved lung function. This study provides a new approach for the application of Quercetin in asthma treatment and reveals the potential regulatory role of the Hippo pathway in asthma-related airway remodeling, demonstrating its broad application prospects in the treatment of respiratory diseases.
哮喘是一种常见的慢性呼吸道疾病，其特征为气道重塑，这会导致不可逆的气道狭窄和肺功能受损。目前的治疗方法未能有效解决这种结构改变。本研究引入了一种创新策略，将具有抗炎和抗增殖特性的天然黄酮类化合物槲皮素与壳聚糖-海藻酸钠纳米颗粒（CA-NPs）相结合，以提高生物利用度和治疗效果。通过激活Hippo信号通路，CA-NPs-槲皮素抑制人气道平滑肌细胞（HASMCs）的增殖和迁移，而HASMCs是气道重塑的关键驱动因素。实验证明，CA-NPs-槲皮素能显著抑制HASMCs的增殖和迁移，凋亡率增加归因于YAP和TAZ的磷酸化，这限制了它们的核转位。实验表明，CA-NPs-槲皮素能显著改善哮喘小鼠的气道炎症，减少支气管肺泡灌洗液中炎症细胞和嗜酸性粒细胞的总数，IL-4表达显著降低（56.65%），IL-10（130.91%）和IFN-γ（156.58%）水平显著上调。此外，CA-NPs-槲皮素减少了肺组织中的胶原沉积（槲皮素组减少42.53%，CA-NPs-槲皮素组减少73.20%）并改善了肺功能。本研究为槲皮素在哮喘治疗中的应用提供了一种新方法，并揭示了Hippo通路在哮喘相关气道重塑中的潜在调节作用，证明了其在呼吸系统疾病治疗中的广阔应用前景。
