ABSTRACT
The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions.
Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Behavior, Animal/drug effects , Nociception/drug effects , Peptides, Cyclic/pharmacology , Proto-Oncogene Proteins c-fos/metabolism , Analgesics/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Gene Expression Regulation/drug effects , Hyperalgesia/drug therapy , Inflammation/drug therapy , Male , Mice , Peptides, Cyclic/therapeutic use , Periaqueductal Gray/drug effects , Periaqueductal Gray/metabolism , Rotarod Performance TestABSTRACT
This study aimed at synthesizing the carvacrol propionate (CP) and evaluating its pharmacological profile. CP was obtained from carvacrol and propionyl chloride through an esterification reaction. Male Swiss mice were treated with CP (25, 50, or 100 mg/kg). We evaluated the analgesic effect, mechanical hyperalgesia, and anti-inflammatory effect. Pre-treatment with CP inhibited (p<0.01 and 0.001) the formalin-induced nociception in both phases. CP inhibited (p<0.05, 0.01, and 0.001) the development of mechanical hyperalgesia. CP was able to decrease the leukocyte recruitment (p<0.001) and the amount of TNF-α (p<0.001), IL-1ß (p<0.05), and protein leakage (p<0.01) into the pleural cavity. In addition, the paw edema was inhibited by CP (p<0.05, 0.01, and 0.001). The CP attenuates nociception, mechanical hyperalgesia, and inflammation, through an inhibition of cytokines.
