Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Institute of Integrative Medicine, Fudan University, Shanghai, China.
J Gene Med. 2024 Jul;26(7):e3718. doi: 10.1002/jgm.3718.
Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments.
The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation.
ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment.
ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.
淫羊藿苷（ICA）可抑制多种疾病的炎症反应，但 ICA 治疗哮喘气道炎症的机制尚需进一步研究。本研究旨在采用网络药理学和实验方法预测和验证 ICA 治疗哮喘相关气道炎症的潜在靶点。
建立卵清蛋白诱导的哮喘相关气道炎症小鼠模型。通过行为学、气道高反应性、肺组织病理变化、炎性细胞和细胞因子计数评估 ICA 的作用。然后，通过 SEA、CTD、HERB、PharmMapper、Symmap 数据库和文献挖掘 ICA 的相应靶点。使用 Pubmed-Gene 和 GeneCards 数据库筛选哮喘和气道炎症相关靶点。对重叠靶点进行构建相互作用网络、基因本体论分析和富集通路分析。然后，采用流式细胞术、实时定量 PCR 和 Western blot 进行验证。
ICA 缓解哮喘的气道炎症；筛选出 ICA 的 402 个靶点、哮喘的 5136 个靶点和气道炎症的 4531 个靶点；匹配并预测 216 个重叠靶点，表明 ICA 具有通过调节肺泡巨噬细胞的激活/极化来调节哮喘气道炎症的潜力。此外，ICA 降低了 M1 但升高了 M2。ICA 治疗可恢复哮喘炎症破坏的潜在靶点。
ICA 通过抑制肺泡巨噬细胞的 M1 极化缓解哮喘中的气道炎症，这与代谢重编程有关。Jun、Jak2、Syk、Tnf、Aldh2、Aldh9a1、Nos1、Nos2 和 Nos3 可能是治疗干预的潜在靶点。本研究增强了对 ICA 抗气道炎症作用的理解，尤其是在哮喘中。
