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 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 , 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.

The aim of the present study was to evaluate the changes caused by adjuvant-induced arthritis in liver mitochondria and to investigate the effects of the nonsteroidal anti-inflammatory drug nimesulide. The main alterations observed in liver mitochondria from arthritic rats were: higher rates of state IV and state III respiration with beta-hydroxybutyrate as substrate; reduced respiratory control ratio and impaired capacity for swelling dependent on beta-hydroxybutyrate oxidation. No alterations were found in the activities of NADH oxidase and ATPase. Nimesulide produced: (1) stimulation of state IV respiration; (2) decrease in the ADP/O ratio and in the respiratory control ratio; (3) stimulation of ATPase activity of intact mitochondria; (4) inhibition of swelling driven by the oxidation of beta-hydroxybutyrate; (5) induction of passive swelling due to NH(3)/NH(4)+ redistribution. The activity of NADH oxidase was insensitive to nimesulide. Mitochondria from arthritic rats showed higher sensitivity to nimesulide regarding respiratory activity. The results of this work allow us to conclude that adjuvant-induced arthritis leads to quantitative changes in some mitochondrial functions and in the sensitivity to nimesulide. Direct evidence that nimesulide acts as an uncoupler was also presented. Since nimesulide was active in liver mitochondria at therapeutic levels, the impairment of energy metabolism could lead to disturbances in the liver responses to inflammation, a fact that should be considered in therapeutic intervention.

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.

Antiinflammatory activities of aqueous and saponin extracts and ecdysterone obtained from Pfaffia iresinoides (Sprengel) were studied by using three experimental inflammatory models in rats. The saponin extract (25 and 50 mg/kg, p.o.) reduced the leukocyte migration, particularly of mononuclear cells in the carrageenin-induced pleurisy. It also inhibited the granuloma tissue formation following cotton pellet implantation and the complete Freund's adjuvant-induced arthritis. The aqueous extract, in the same conditions, was effective on both carrageenin-induced pleurisy and complete Freund's adjuvant arthritis. However, it did not alter the granuloma formation. The ecdysterone (5 mg/kg, p.o.), isolated from P. iresinoides, showed no effect on these inflammatory processes.

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