{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:45:08Z","timestamp":1790477108571,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Backgrounds<\/jats:title><jats:p>11,12\u2010Diacetyl\u2010carnosol (DACA), a derivative of carnosol, exhibits significant anti\u2010inflammatory and antioxidant properties. However, its antidepressant effects and underlying mechanisms remain unclear. High mobility group box\u00a01 protein (HMGB1)\u2010mediated inflammatory responses and associated neurofunctional impairments play a crucial role in the pathogenesis of depression. This study aimed to investigate whether DACA exerts anti\u2010inflammatory and antidepressant effects and whether its mechanisms involve the HMGB1\/NF\u2010\u03baB\/NLRP3 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>(1) A depression model was established in mice through 6\u2009weeks of chronic unpredictable mild stress (CUMS). From the 4th week of stimulation, the treatment group received DACA for 3\u2009weeks. (2) BV2 cells were stimulated with LPS+ATP, and the treatment group was cultured in DACA medium for 24\u2009h. (3) Supernatants from BV2 cells were used to culture primary neurons. To confirm the critical role of HMGB1 in DACA's antidepressant effects, CUMS\u2010stressed mice were treated with glycyrrhizin (GZA) or the DACA+GZA combination. Depressive\u2010like behaviors were evaluated using the sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), forced swim test (FST), and Morris water maze (MWM). Hippocampal microglial cell and primary neuron morphology were assessed by immunofluorescence, and dendritic spine density in hippocampal neurons was examined using Golgi staining. IL\u20106 and TNF\u2010\u03b1 concentrations in mouse serum and BV2 supernatant were measured by ELISA. Western blotting was used to detect protein expressions of HMGB1, NF\u2010\u03baB p65, p\u2010NF\u2010\u03baB p65, NLRP3, and IL\u20101\u03b2 in the hippocampus and BV2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CUMS\u2010exposed mice showed decreased sucrose preference, increased immobility in TST and FST, prolonged escape latency in MWM, and reduced crossings. Microglial activation and upregulation of HMGB1, NF\u2010\u03baB p65, p\u2010NF\u2010\u03baB p65, NLRP3, and IL\u20101\u03b2 were observed in both CUMS\u2010stressed mice and LPS+ATP\u2010induced BV2 cells, with reduced dendritic spine density in the hippocampus. DACA significantly reversed these phenomena. The effects of DACA were comparable to those of GZA treatment, and no changes were observed with the DACA+GZA combination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The HMGB1\/NF\u2010\u03baB\/NLRP3 signaling pathway is involved in DACA's therapeutic effects on depression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70406","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:29:25Z","timestamp":1747981765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["11,12\u2010Diacetyl\u2010Carnosol Ameliorates Depression\u2010Like Behaviors and Memory Dysfunction in <scp>CUMS<\/scp> Mouse Model via Inhibiting <scp>HMGB1<\/scp>\u2010Mediated Neuroinflammation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7285-4561","authenticated-orcid":false,"given":"Kunying","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science &amp; Yunnan Provincial Key Laboratory of Pharmacology for Natural Products Kunming Medical University  Kunming People's Republic of China"},{"name":"College of Modern Biomedical Industry Kunming Medical University  Kunming People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science &amp; Yunnan Provincial Key Laboratory of Pharmacology for Natural Products Kunming Medical University  Kunming People's Republic of China"},{"name":"College of Modern Biomedical Industry Kunming Medical University  Kunming People's Republic of 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