Abstract
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.
Highlights
Jasmonates are fatty acid-derived cyclopentanones widely distributed over the plant kingdom where they act as signaling molecules in response to abiotic and biotic stresses [1]
Because methyl jasmonate (MeJA) has been reported to stimulate mitochondrial reactive oxygen species (ROS) production [1], this study has evaluated the production of ROS and the respiratory activity in isolated hepatic mitochondria of healthy and arthritic rats
This increase was considerably less pronounced in arthritic rats treated with 300 mg·kg−1 MeJA or ibuprofen (88%)
Summary
Jasmonates are fatty acid-derived cyclopentanones widely distributed over the plant kingdom where they act as signaling molecules in response to abiotic and biotic stresses [1]. The jasmonate family consists mainly of jasmonic acid, cis-jasmonate, and methyl jasmonate (MeJA), which share structural similarities with prostaglandins, especially with those that have anti-inflammatory activities (Figure 1) [2]. For this reason, many studies have been carried out to evaluate their actions on mammal cells. MeJA, showed to be superior to other jasmonates, and MeJA and its synthetic derivatives have been lately more intensely investigated as promising agents for cancer treatment [2]. MeJA induces apoptosis and inhibits proliferation in murine and human cancer cell lines, including those of breast, colon, prostate, and lymphoma [2]. MeJA increases the survival period of mice bearing the EL-4 lymphoma and of mice inoculated with multiple myeloma (MM.1S) cells [3, 4]
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