Methyl Jasmonate Reduces Inflammation and Oxidative Stress in the Brain of Arthritic Rats.

Methyl jasmonate (MeJA), common in the plant kingdom, is capable of reducing articular and hepatic inflammation and oxidative stress in adjuvant-induced arthritic rats. This study investigated the actions of orally administered MeJA (75-300 mg/kg) on inflammation, oxidative stress and selected enzyme activities in the brain of Holtzman rats with adjuvant-induced arthritis. MeJA prevented the arthritis-induced increased levels of nitrites, nitrates, lipid peroxides, protein carbonyls and reactive oxygen species (ROS). It also prevented the enhanced activities of myeloperoxidase and xanthine oxidase. Conversely, the diminished catalase and superoxide dismutase activities and glutathione (GSH) levels caused by arthritis were totally or partially prevented. Furthermore, MeJA increased the activity of the mitochondrial isocitrate dehydrogenase, which helps to supply NADPH for the mitochondrial glutathione cycle, possibly contributing to the partial recovery of the GSH/oxidized glutathione (GSSG) ratio. These positive actions on the antioxidant defenses may counterbalance the effects of MeJA as enhancer of ROS production in the mitochondrial respiratory chain. A negative effect of MeJA is the detachment of hexokinase from the mitochondria, which can potentially impair glucose phosphorylation and metabolism. In overall terms, however, it can be concluded that MeJA attenuates to a considerable extent the negative effects caused by arthritis in terms of inflammation and oxidative stress.

Anti-Inflammatory and Antioxidant Actions of Methyl Jasmonate Are Associated with Metabolic Modifications in the Liver of Arthritic Rats.

Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares structural similarities with prostaglandins and has been under study as a promising anti-inflammatory agent. This study investigated the actions of MeJA on systemic inflammation and oxidative status in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg·kg-1) was administrated orally during 18 days after arthritis induction with Freund's adjuvant. Articular and systemic inflammation was greatly increased in arthritic rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase activity and glycolysis were increased in arthritic rats. MeJA decreased most inflammatory parameters and abolished the increased protein carbonylation in plasma and liver, diminished the increased hepatic ROS content, and restored the hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS production in healthy and arthritic rats. Oxygen uptake was increased by MeJA only in livers from treated arthritic rats. This action may bear relation to the increased activity of mitochondrial NADP+-dependent enzymes to provide reducing equivalents for the glutathione cycle. These beneficial effects, however, are associated with a decreased glucose flux through the glycolysis in the liver of arthritic and healthy rats.

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

The current study investigated the action of ß-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 ß-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 ß-caryophyllene orally once a day during 18 days. Both doses of ß-caryophyllene reduced the adjuvant-induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. ß-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, ß-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 ß-caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, ß-caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that ß-caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.