Xu Lili, An Yujuan, Liu Ting, Zhang Yanan, Chen Xiaoyu, Liu Xing, Wei Gang, Ge Hongzhou
Department of Pharmacy Intravenous Admixture Services, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao 266033, Shandong, PR China.
Department of Otolaryngology, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao 266033, Shandong, PR China.
Toxicol Appl Pharmacol. 2025 Nov;504:117510. doi: 10.1016/j.taap.2025.117510. Epub 2025 Aug 11.
Allergic rhinitis (AR) is a significant global health issue that necessitates effective treatments. This paper investigates the mechanism of arctigenin (ATG) in alleviating AR. An AR mouse model was constructed and administered with different doses of ATG or positive control dexamethasone. Human nasal epithelial cells (HNEpCs) were stimulated with IL-4 and IL-13 to mimic AR-induced epithelial cell damage. Bioinformatic analysis was performed to predict target proteins of ATG and downstream factors of KLF5. AR mice and HNEpCs were treated with KLF5 overexpression lentivirus and BIRC3 knockdown lentivirus. HNEpCs were treated with NF-κB pathway agonist TWEAK. Our results revealed that ATG remodeled the nasal epithelial barrier function and alleviated inflammation in AR mice and inhibited IL-4/IL-13-induced inflammatory injury in HNEpCs. Mechanistically, ATG inhibited the expression of KLF5 protein. KLF5 transcriptionally activated BIRC3 and the NF-κB pathway. KLF5 overexpression exacerbated inflammatory injury in AR mice and HNEpCs, which was reversed by BIRC3 knockdown. NF-κB pathway agonist exacerbated inflammatory injury in HNEpCs. In conclusion, ATG remodels the nasal epithelial barrier function and alleviates AR in mice by inhibiting KLF5 protein expression and BIRC3 transcription and impairing the NF-κB pathway.
过敏性鼻炎（AR）是一个重大的全球健康问题，需要有效的治疗方法。本文研究了牛蒡子苷元（ATG）缓解AR的机制。构建AR小鼠模型，并给予不同剂量的ATG或阳性对照地塞米松。用白细胞介素-4（IL-4）和白细胞介素-13（IL-13）刺激人鼻上皮细胞（HNEpCs），以模拟AR诱导的上皮细胞损伤。进行生物信息学分析以预测ATG的靶蛋白和KLF5的下游因子。用KLF5过表达慢病毒和BIRC3敲低慢病毒处理AR小鼠和HNEpCs。用核因子κB（NF-κB）途径激动剂肿瘤坏死因子样弱凋亡诱导因子（TWEAK）处理HNEpCs。我们的结果表明，ATG重塑了AR小鼠的鼻上皮屏障功能，减轻了炎症，并抑制了IL-4/IL-13诱导的HNEpCs炎症损伤。机制上，ATG抑制KLF5蛋白的表达。KLF5转录激活BIRC3和NF-κB途径。KLF5过表达加剧了AR小鼠和HNEpCs的炎症损伤，而BIRC3敲低可逆转这种损伤。NF-κB途径激动剂加剧了HNEpCs的炎症损伤。总之，ATG通过抑制KLF5蛋白表达和BIRC3转录并损害NF-κB途径，重塑鼻上皮屏障功能并减轻小鼠的AR。
