Icariside II targets M2 macrophages by regulating the inflammasome and profibrotic signaling in chronic asthma

作者：Mengmeng Chen, Heng Zhang, Congcong Li, Jiaqi Liu, Huahe Zhu, Weifeng Tang, Xueyi Zhu, Jiemin He, Yuting Shi, Yalikun Maimaititusun, Na Wang, Jingcheng Dong · 发表于：Phytomedicine · 年份：2026 · DOI：10.1016/j.phymed.2026.157787 · 被引用次数：2 · 研究领域：Asthma and respiratory diseases、Immune cells in cancer、Natural Compounds in Disease Treatment

BACKGROUND: Chronic asthma features persistent airway inflammation, airway hyper-responsiveness, and structural remodeling. Macrophages, especially alternatively activated M2 cells, are key drivers of type-2 immunity and fibrosis. Icariside II (ICAII), a flavonoid from Epimedium, exhibits known anti-inflammatory properties, but its precise immunomodulatory effects on M2 macrophages in asthma remain elusive. OBJECTIVE: This work sought to evaluate the potential therapeutic role of ICAII using a mouse model that mimics chronic asthma and define the underlying mechanisms, with emphasis on macrophage polarization and immune-mediated tissue remodeling. METHODS: Chronic asthma was established in BALB/c mice through ovalbumin (OVA) sensitization and repeated exposure, followed by ICAII administration at various doses. Pulmonary function tests, histological analyses, ELISA, flow cytometry, and immunohistochemistry were employed to assess inflammation, airway remodeling, and macrophage polarization. In vitro experiments using RAW264.7 and MHS macrophage lines further investigated ICAII's impact on M2 differentiation. Transcriptome sequencing, network pharmacology, molecular docking analyses, and validation were integrated to identify key regulatory pathways. RESULTS: ICAII improved airway resistance and compliance, alleviated inflammatory infiltration and collagen deposition, and lowered Th2 cytokines, serum IgE, and pro-fibrotic markers, with the most pronounced effects observed at 4...