{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:40:18Z","timestamp":1790109618015,"version":"4.0.1"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"8","content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CMM"],"published-print":{"date-parts":[[2020,12,29]]},"abstract":"<jats:sec>\n<jats:title>Backgrounds and Objective:<\/jats:title>\n<jats:p>Inflammation is implicated in the pathogenesis\nof many diseases. Inflammatory cytokines with painful conditions are well known as\nbiomarkers in human muscle pain, and they are produced by macrophages. Metaxalone\nis used as a skeletal muscle relaxant, but the mechanism by which metaxalone acts is\nunknown. This study was undertaken to investigate whether or not metaxalone exhibits\nan inhibitory effect on the activity of inflammatory macrophages in vitro.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>Mouse macrophage RAW264.7 cells were cultured in Dulbecco\u2019s Modification\nof Eagle\u2019s Medium containing 10% fetal bovine serum in the presence of metaxalone.\nCell growth was assayed by counting the number of cells attached to culture dishes.\nInflammatory cytokines released into the culture medium were analyzed with the ELISA\nkit.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p> Metaxalone (1-100 \u03bcM) was found to decrease the number of macrophages by\ninhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro. The\ncombination of metaxalone (0.1 or 1 \u03bcM) and \u03b2-caryophyllene (10 or 50 \u03bcM), which\nalone did not have a significant effect on the cell number, caused potential effects on the\ngrowth and death of RAW264.7 cells. Mechanistically, molecular levels of mitogenactivated\nprotein kinase were decreased by treatment with metaxalone or \u03b2-\ncaryophyllene, and each effect was enhanced by their combination. Furthermore, levels\nof caspase-3 were increased by metaxalone or \u03b2-caryophyllene and enhanced by their\ncombination. Notably, productions of inflammatory cytokines, including tumor necrosis\nfactor-\u03b1, interleukin-6 or prostaglandin E2, which were enhanced by lipopolysaccharide\n(LPS), were repressed by culturing with metaxalone. Levels of cyclooxygenase (COX)-1,\nCOX-2 and nuclear factor kappa B, which were increased by LPS treatment, were\nreduced by metaxalone.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Metaxalone was found to suppress the activity of inflammatory\nmacrophages in vitro.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1566524020666200217102508","type":"journal-article","created":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T13:22:46Z","timestamp":1581945766000},"page":"643-652","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metaxalone Suppresses Production of Inflammatory Cytokines Associated with Painful Conditions in Mouse Macrophages RAW264.7 Cells in Vitro: Synergistic Effect with \u03b2-caryophyllene"],"prefix":"10.2174","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8511-110X","authenticated-orcid":true,"given":"Masayoshi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), 700 Tiverton Avenue, Los Angeles, CA 90095-1732, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Clinical Development, Primus Pharmaceuticals, Inc., Scottsdale, AZ 85251, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","container-title":["Current Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eurekaselect.com\/article\/download\/179400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/179400\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eurekaselect.com\/article\/download\/179400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,30]],"date-time":"2020-12-30T04:25:24Z","timestamp":1609302324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/179400\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,29]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,12,29]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/1566524020666200217102508","relation":{},"ISSN":["1566-5240"],"issn-type":[{"value":"1566-5240","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12,29]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2019-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-20","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}