RESUMO
CONTEXT: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae). OBJECTIVE: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K⺠channel pathway. MATERIALS AND METHODS: We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 µl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E2 (PGE2; 100 ng/paw) or dopamine (DA; 30 µg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). RESULTS: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE2 test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE2 test. DISCUSSION AND CONCLUSION: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K⺠channel pathway.
Assuntos
Aldeídos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , GMP Cíclico/metabolismo , Modelos Animais de Doenças , Canais KATP/metabolismo , Monoterpenos/uso terapêutico , Óxido Nítrico/metabolismo , Dor Nociceptiva/prevenção & controle , Monoterpenos Acíclicos , Aldeídos/administração & dosagem , Aldeídos/antagonistas & inibidores , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , GMP Cíclico/antagonistas & inibidores , Cymbopogon/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Glibureto/farmacologia , Indonésia , Canais KATP/antagonistas & inibidores , Masculino , Camundongos , Monoterpenos/administração & dosagem , Monoterpenos/antagonistas & inibidores , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Dor Nociceptiva/imunologia , Dor Nociceptiva/metabolismo , Óleos Voláteis/química , Limiar da Dor/efeitos dos fármacos , Óleos de Plantas/química , Bloqueadores dos Canais de Potássio/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
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.