{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T02:25:08Z","timestamp":1787192708890,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Acute lung injury (ALI) is life-threatening disease characterized by uncontrolled inflammatory response. IKK\u03b1\/\u03b2, the key kinases in the activation of NF-\u03baB pathway, are implicated in inflammatory pulmonary injury, and represent attractive targets for ALI therapy. Brevilin A (BVA) is a sesquiterpene lactone from <jats:italic>Centipeda minima<\/jats:italic>, a Chinese herb used to treat inflammatory diseases. This study aims to investigate the inhibition of BVA on ALI, with focus on clarifying the molecular mechanisms involved in BVA-mediated anti-inflammatory activity in macrophages. Briefly, BVA significantly inhibited the production of NO and PGE<jats:sub>2<\/jats:sub> by suppressing iNOS and COX2 expression, and suppressed the mRNA expression of IL-1\u03b2, IL-6, and TNF\u03b1 in LPS\/IFN\u03b3-stimulated RAW264.7 macrophages. The anti-inflammatory activity of BVA was further confirmed in LPS\/IFN\u03b3-stimulated BMDMs and TNF\u03b1\/IFN\u03b3-exposed RAW264.7 cells. <jats:italic>In vivo<\/jats:italic>, BVA effectively attenuated LPS-induced lung damage, inflammatory infiltration, and production of pro-inflammatory cytokines, including MPO, IL-1\u03b2, IL-6, TNF\u03b1, and PGE<jats:sub>2<\/jats:sub>. Mechanistically, BVA could covalently bind to the cysteine 114 of IKK\u03b1\/\u03b2, and effectively inhibiting the activity and function of IKK\u03b1\/\u03b2, thereby resulting in the suppression of phosphorylation and degradation of I\u03baB\u03b1 and the subsequent activation of NF-\u03baB signaling. Furthermore, pretreatment of DTT, a thiol ligand donor, significantly abolished BVA-mediated effects in LPS\/IFN\u03b3-stimulated RAW264.7 cells, suggesting the crucial role of the electrophilic \u03b1, \u03b2-unsaturated ketone of BVA on its anti-inflammatory activity. These results suggest that BVA ameliorates ALI through inhibition of NF-\u03baB signaling via covalently targeting IKK\u03b1\/\u03b2, raising the possibility that BVA could be effective in the treatment of ALI and other diseases harboring aberrant NF-\u03baB signaling.<\/jats:p>","DOI":"10.3389\/fphar.2022.911157","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T07:34:11Z","timestamp":1655192051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Brevilin A Ameliorates Acute Lung Injury and Inflammation Through Inhibition of NF-\u03baB Signaling via Targeting IKK\u03b1\/\u03b2"],"prefix":"10.3389","volume":"13","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyuan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunguang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.imbio.2017.11.001","article-title":"Macrophages: Their Role, Activation and Polarization in Pulmonary Diseases","volume":"223","author":"Arora","year":"2018","journal-title":"Immunobiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-activated Protein Kinases in Innate Immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. 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