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J Cell Biochem. 2018 Dec;119(12):10262-10277. doi: 10.1002/jcb.27369. Epub 2018 Aug 21.

β-Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats.

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Department of Biochemistry, State University of Maringá, Maringá, Paraná, Brazil.
Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Paraná, Brazil.
Department of Morphological Sciences, State University of Maringá, Maringá, Paraná, Brazil.


The current study investigated the action of β-caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β-caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg-1 β-caryophyllene orally once a day during 18 days. Both doses of β-caryophyllene reduced the adjuvant-induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. β-Caryophyllene, at the dose of 430 mg·kg -1 , 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 ( Copaifera reticulata) and, therefore, β-caryophyllene is possibly responsible for the anti-inflammatory 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 (-23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by β-caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, β-caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that β-caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.


adjuvant-induced arthritis; copaiba oil; gluconeogenesis; liver metabolism; liver oxidative status; β-caryophyllene


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