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They are significantly restricted in clinical usage due to its drug tolerance and certain side effects. As an important pathological feature of asthma, it is not currently targeted by any frontline treatments, targeting oxidative stress mechanisms may represent a novel therapeutic intervention for asthma.\n                    <jats:italic>Icariin<\/jats:italic>\n                    is a prenylated flavonol glycoside from the chinese herb Epimedium, which has been shown to have anti\u2010oxidative stress activities. Our previous study showed that\n                    <jats:italic>Icariin<\/jats:italic>\n                    effectively inhibits airway inflammation of asthmatic mice, but the mechanism is still not fully understood. This study was to determine whether\n                    <jats:italic>Icariin<\/jats:italic>\n                    can play an anti\u2010oxidative stress role in asthmatic airway epithelium and inhibits NF\u2010\u03baB signaling by promoting the expression of Nrf2. The oxidative stress status of asthmatic patients were observed. OVA was used for induction of mouse allergic asthma models, and the human bronchial epithelial cell line HBE was used for in\u00a0vitro studies. The potential mechanism of\n                    <jats:italic>Icariin<\/jats:italic>\n                    was explored by in\u00a0vivo and in\u00a0vitro studies. Our results showed that there is an imbalance of oxidative\/antioxidant factors in both asthmatic patients and mice.\n                    <jats:italic>Icariin<\/jats:italic>\n                    alleviated airway inflammation while reversing oxidative\/antioxidant factors in asthmatic mice. Mechanically,\n                    <jats:italic>Icariin<\/jats:italic>\n                    significantly promoted the expression of Nrf2 in asthmatic mice and airway epithelial cells, while significantly inhibited the expression of NF\u2010\u03baB signaling. Further, the inhibitory effect of Icariin on phosphorylated NF\u2010\u03baB p65 was significantly weakened after knockdown of Nrf2. However,\n                    <jats:italic>Icariin<\/jats:italic>\n                    had no effect on the methylation of the DNA promoter regions of Keap\u20101 or Nrf2. Overall, the study demonstrated that Icariin could inhibit NF\u2010\u03baB signaling by promoting the activation of Nrf2 signaling, thereby exerting an anti\u2010asthmatic effect. However, this promoting effect of ICA on Nrf2 activation is independent of DNA\u2010methylation of Keap\u20101 or Nrf2.\n                    <jats:italic>Icariin<\/jats:italic>\n                    might be a promising intervention for the treatment of asthma by activating Nrf2 signaling to inhibit NF\u2010\u03baB signaling, targeting oxidative stress mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70124","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T04:52:06Z","timestamp":1766033526000},"page":"545-559","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Icariin Inhibits\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Signaling in Asthmatic Lung Epithelium by Promoting Nrf2 Signaling"],"prefix":"10.1002","volume":"40","author":[{"given":"Shiyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine Huashan Hospital, Fudan University  Shanghai China"},{"name":"Institutes of Integrative Medicine Fudan University  Shanghai China"},{"name":"Department of Rehabilitation Medicine Sir Run Run Shaw Hospital, Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine Huashan Hospital, Fudan University  Shanghai China"},{"name":"Institutes of Integrative Medicine Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Integrative Medicine Huashan Hospital, Fudan University  Shanghai China"},{"name":"Institutes of Integrative 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