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This study also compared the actions of \u03b2\u2010caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received\u00a0215 and 430\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup> \u03b2\u2010caryophyllene orally once a day during 18 days. Both doses of \u03b2\u2010caryophyllene reduced the adjuvant\u2010induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. \u03b2\u2010Caryophyllene, at the dose of 430\u2009mg\u00b7kg\n<jats:sup>\u22121<\/jats:sup>, abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil (\n<jats:italic>Copaifera reticulata<\/jats:italic>) and, therefore, \u03b2\u2010caryophyllene is possibly responsible for the anti\u2010inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (\u221223%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by \u03b2\u2010caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, \u03b2\u2010caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that \u03b2\u2010caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.<\/jats:p>","DOI":"10.1002\/jcb.27369","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T16:09:08Z","timestamp":1534954148000},"page":"10262-10277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":105,"title":["\u03b2\u2010Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats"],"prefix":"10.1002","volume":"119","author":[{"given":"Ana P.","family":"Ames\u2010Sibin","sequence":"first","affiliation":[{"name":"Department of Biochemistry State University of Maring\u00e1 Maring\u00e1 Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila L.","family":"Bariz\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Biochemistry State University of Maring\u00e1 Maring\u00e1 Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane V.","family":"Castro\u2010Ghizoni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry State University of Maring\u00e1 Maring\u00e1 Paran\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francielli M. 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