巴马汀通过抑制Alox15介导的铁死亡恢复哮喘气道上皮屏障功能
Palmatine restores airway epithelial barrier function of asthma by inhibiting Alox15-mediated ferroptosis.
摘要(中文译文)
上皮屏障功能障碍在哮喘发病机制中发挥关键作用。巴马汀（Palmatine）已被证实在结肠炎中可增强上皮完整性，并改善荨麻疹样皮肤炎症，提示其具有潜在的屏障保护作用。本研究旨在探讨巴马汀在嗜酸性哮喘中的屏障保护作用。建立卵清蛋白诱导的嗜酸性哮喘模型。给予巴马汀后，评估肺功能、气道反应性、黏液分泌、胶原沉积及上皮屏障完整性。采用蛋白质组学、分子对接、细胞实验和免疫荧光阐明其潜在机制。巴马汀通过上调E-钙黏蛋白（E-cadherin）、闭合蛋白（occludin）和ZO-1显著恢复上皮屏障完整性。相应地，它改善了大、小气道阻塞，并降低了气道高反应性。它还降低了IL-5、IL-13和MMP9水平，表明炎症和胶原沉积减轻。蛋白质组学和机制研究揭示，巴马汀抑制了气道上皮细胞中Alox15介导的铁死亡，表现为肺组织中GSSG、MDA和LPO降低及GSH水平升高。在erastin处理的BEAS-2B细胞中，巴马汀抑制Alox15和PEBP1表达，同时伴随上皮连接蛋白E-cadherin、occludin和ZO-1的恢复。巴马汀在嗜酸性哮喘中表现出治疗作用。通过抑制Alox15介导的铁死亡，它恢复气道上皮屏障完整性并减轻炎症和气道高反应性，凸显其作为嗜酸性哮喘潜在治疗药物的前景。
Abstract
Epithelial barrier dysfunction plays a key role in asthma pathogenesis. Palmatine has been shown to reinforce epithelial integrity in colitis and ameliorate urticaria-like skin inflammation, suggesting potential barrier-protective effects. To investigate the barrier-protective role of palmatine in eosinophilic asthma. An ovalbumin-induced eosinophilic asthma model was established. After palmatine administration, lung function, airway responsiveness, mucus secretion, collagen deposition, and epithelial barrier integrity were assessed. Proteomics, molecular docking, cellular experiments, and immunofluorescence were performed to elucidate underlying mechanisms. Palmatine markedly restored epithelial barrier integrity by upregulating E-cadherin, occludin, and ZO-1. Correspondingly, it improved both large- and small-airway obstruction, and reduced airway hyperresponsiveness. It also reduced IL-5, IL-13, and MMP9 levels, indicating attenuation of inflammation and collagen deposition. Proteomics and mechanistic studies revealed that palmatine suppressed Alox15-mediated ferroptosis in airway epithelial cells, reflected by reduced GSSG, MDA, and LPO and increased GSH levels in lung tissue. In erastin-treated BEAS-2B cells, palmatine inhibited Alox15 and PEBP1 expression accompanied by recovery of epithelial junction proteins E-cadherin, occludin, and ZO-1. Palmatine exhibits therapeutic effects in eosinophilic asthma. By inhibiting Alox15-mediated ferroptosis, it restores airway epithelial barrier integrity and alleviates inflammation and airway hyperresponsiveness, highlighting its promise as a potential therapeutic agent for eosinophilic asthma.
如何引用
AMA
Lei Zhao, Jifei Wu, Yichen Zhang, Yongchang Zhao, Yanmei Lin, Min Zhang, et al. Palmatine restores airway epithelial barrier function of asthma by inhibiting Alox15-mediated ferroptosis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158518.
APA
Lei Zhao, Jifei Wu, Yichen Zhang, Yongchang Zhao, Yanmei Lin, Min Zhang, et al (2026). Palmatine restores airway epithelial barrier function of asthma by inhibiting Alox15-mediated ferroptosis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158518
GB/T 7714
Lei Zhao, Jifei Wu, Yichen Zhang, Yongchang Zhao, Yanmei Lin, Min Zhang, et al. Palmatine restores airway epithelial barrier function of asthma by inhibiting Alox15-mediated ferroptosis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158518.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出