{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:08:10Z","timestamp":1790053690655,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Crystal-induced arthropathies, including gout and calcium pyrophosphate deposition disease, are characterized by activation of inflammatory and oxidative pathways involving nuclear factor-kappa B (NF-\u03baB) signaling, inflammasome activation, and reactive oxygen species (ROS) generation. This study evaluated the anti-inflammatory and antioxidant effects of 2,4,5-trimethoxy-2\u2032-trifluoromethylchalcone (CH) in experimental models of crystal-induced inflammation and gouty arthritis. CH was evaluated in lipopolysaccharide (LPS)\/adenosine 5\u2032-triphosphate (ATP)-stimulated murine peritoneal macrophages and in murine models of CPPD crystal-induced air pouch inflammation and monosodium urate (MSU)-induced gouty arthritis. Cytokine production was determined by ELISA, whereas NF-\u03baB and caspase-1 activation were evaluated by Western blot. ROS generation and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) were also assessed. CH reduced interleukin (IL)-1\u03b2, IL-18, tumor necrosis factor (TNF)-\u03b1, and IL-6 production in activated macrophages and attenuated lactate dehydrogenase release associated with pyroptosis. Mechanistically, CH reduced p65 NF-\u03baB phosphorylation, caspase-1 activation, and ROS generation while promoting Nrf2 nuclear translocation. In vivo, CH reduced leukocyte infiltration, myeloperoxidase activity, inflammatory cytokine levels, and paw edema in CPPD- and MSU-induced models. These findings suggest that CH acts as a multitarget compound capable of simultaneously modulating inflammatory and oxidative pathways involved in crystal-induced arthropathies, which may represent a potential advantage over approaches targeting a single inflammatory pathway.<\/jats:p>","DOI":"10.3390\/antiox15091197","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["2,4,5-trimethoxy-2\u2032-trifluoromethylchalcone Attenuates Oxidative Stress and Inflammasome-Associated Inflammation in Experimental Models of Crystal-Induced Inflammation"],"prefix":"10.3390","volume":"15","author":[{"given":"Laura","family":"Catal\u00e1n","sequence":"first","affiliation":[{"name":"Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. 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