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We examined the anti\u2010inflammatory molecular mechanisms of DHK employing in\u00a0vitro RAW264.7 macrophages and in\u00a0vivo BALB\/c mice under LPS\/ATP stimulation. We found that DHK suppressed NLRP3 inflammasome, procaspase\u20101 activation and then pro\u2010inflammatory IL1\u03b2 expression in LPS\/ATP\u2010stimulated RAW264.7 cells. Notably, DHK\u2010triggered autophagy in RAW264.7 cells was demonstrated by increased LC3\u2010II accumulation, p62\/SQSTM1 expression, Beclin\u20101\/Bcl\u20102 ratio and PI3K\/AKT\/mTOR phosphorylation. Besides, DHK increased Parkin and Pink\u20101 protein expressions implying mitophagy induction in RAW264.7 cells. Interestingly, DHK enhanced Nrf2 nuclear translocation and provoked antioxidant HO\u20101, NQO\u20101 and \u03b3\u2010GCLC expressions in RAW264.7 cells. Nrf2 knockdown reversed DHK\u2010inhibited LPS\/ATP\u2010stimulated IL1\u03b2 expression in RAW264.7 cells. Interestingly, LPS\/ATP\u2010stimulated NLRP3 inflammasome and IL1\u03b2 expression were inhibited by DHK, Mito\u2010TEMPO (a mitochondrial ROS inhibitor), or <jats:italic>N<\/jats:italic>\u2010acetylcysteine (a ROS inhibitor). In\u00a0vivo study revealed that DHK attenuated wet\/dry weight ratio of lung tissue, lung neutrophil intrusions and pulmonary oedema, and reduced the increased total cells, neutrophils, TNF\u03b1 and IL1\u03b2 expression in bronchoalveolar lavage fluid (BALF) in LPS\u2010stimulated BALB\/c mice. DHK alleviated LPS\u2010induced pathological alterations of lung through inhibiting NLRP3 inflammation, enhancing antioxidant Nrf2 pathway and inducing mitophagy in LPS\u2010stimulated BALB\/c mice. Dihydromikanolide may be a potential therapeutic agent for inflammatory diseases.<\/jats:p>","DOI":"10.1111\/jcmm.70803","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:19:53Z","timestamp":1756217993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dihydromikanolide Inhibits <scp>ROS<\/scp>\u2010Mediated <scp>NLRP3<\/scp> Inflammation via Antioxidant Nrf2 Activation and Mitophagy Induction in <scp>LPS<\/scp>\/<scp>ATP<\/scp>\u2010Stimulated Macrophages"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5307-6162","authenticated-orcid":false,"given":"You\u2010Cheng","family":"Hseu","sequence":"first","affiliation":[{"name":"Department of Cosmeceutics, College of Pharmacy China Medical University  Taichung Taiwan"},{"name":"Department of Health and Nutrition Biotechnology Asia University  Taichung Taiwan"},{"name":"Chinese Medicine 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