{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:10:34Z","timestamp":1782835834021,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Experimental and clinical studies have suggested that several neurological disorders are associated with the occurrence of central nervous system neuroinflammation. Metaxalone is an FDA-approved muscle relaxant that has been reported to inhibit monoamine oxidase A (MAO-A). The aim of this study was to investigate whether metaxalone might exert antioxidant and anti-inflammatory effects in HMC3 microglial cells. An inflammatory phenotype was induced in HMC3 microglial cells through stimulation with interleukin-1\u03b2 (IL-1\u03b2). Control cells and IL-1\u03b2-stimulated cells were subsequently treated with metaxalone (10, 20, and 40 \u00b5M) for six hours. IL-1\u03b2 stimulated the release of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-\u03b1) and interleukin-6 (IL-6), but reduced the anti-inflammatory cytokine interleukin-13 (IL-13). The upstream signal consisted of an increased priming of nuclear factor-kB (NF-kB), blunted peroxisome proliferator-activated receptor gamma (PPAR\u03b3), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\u03b1) expression. IL-1\u03b2 also augmented MAO-A expression\/activity and malondialdehyde levels and decreased Nrf2 mRNA expression and protein levels. Metaxalone decreased MAO-A activity and expression, reduced NF-kB, TNF-\u03b1, and IL-6, enhanced IL-13, and also increased PPAR\u03b3, PGC-1\u03b1, and Nrf2 expression. The present experimental study suggests that metaxalone has potential for the treatment of several neurological disorders associated with neuroinflammation.<\/jats:p>","DOI":"10.3390\/ijms22168425","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T09:35:32Z","timestamp":1628156132000},"page":"8425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["MAO-A Inhibition by Metaxalone Reverts IL-1\u03b2-Induced Inflammatory Phenotype in Microglial Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-2265","authenticated-orcid":false,"given":"Giovanni","family":"Pallio","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-1316","authenticated-orcid":false,"given":"Angela","family":"D\u2019Ascola","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-5674","authenticated-orcid":false,"given":"Luigi","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Mannino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bitto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"},{"name":"SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letteria","family":"Minutoli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Picciolo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Squadrito","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-7080","authenticated-orcid":false,"given":"Natasha","family":"Irrera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"},{"name":"SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8868-0762","authenticated-orcid":false,"given":"Francesco","family":"Squadrito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy"},{"name":"SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Altavilla","sequence":"additional","affiliation":[{"name":"SunNutraPharma, Academic Spin-Off Company of the University of Messina, Via C. Valeria, 98125 Messina, Italy"},{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. 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