RESUMO
Myrsinoic acid B (AMB) is a prenylated-benzoic acid derivative isolated from the Rapanea genus. Recent studies suggest that AMB has antihyperalgesic and antinociceptive properties in different animal models. The present study was designed to investigate the mechanisms involved in antinociception elicited by AMB (60 mg/kg) when administered by intraperitonial route (i.p.) in mice. The antinociceptive response of the compound was characterized by a reduction in contractions of the abdominal muscle, together with stretching of the hind limbs in response to i.p. injection of acetic acid (0.6%, 0.45 ml/mouse). The antinociception caused by AMB in the acetic acid test was significantly attenuated by i.p. treatment of mice with nitric oxide precursor, (L-arginine, 600 mg/kg), alpha2 and alpha1-adrenoceptor antagonists (yohimbine, 0.2 mg/kg/prazosin, 0.2 mg/kg), p-chlorophenylalanine (PCPA) an inhibitor of serotonin synthesis (100 mg/kg), 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN 190), a 5-HT1(A) selective receptor antagonist (0.5 mg/kg) and a non-selective cholinergic antagonist (atropine, 10 mg/kg). Its action was also modulated by the adrenal-gland hormones. In contrast, antinociception was not affected by naloxone (non-selective opioid receptor antagonist, 1.0 mg/kg), phaclofen (2.0 mg/kg) and bicuculline (1.0 mg/kg) GABA(B) and GABA(A) receptor antagonists, respectively, ondansetron (0.3 mg/kg) and ketaserin (1.0 mg/kg), (5-HT3 and 5-HT2 receptors, respectively) and haloperidol (0.2 mg/kg), a non-selective dopaminergic receptor. The antinociceptive effects are not related to muscle-relaxant or sedative action. These results indicate that AMB produces antinociception through mechanisms that involve interaction with L-arginine-nitric oxide, the serotonergic and cholinergic systems, as well as interaction with the alpha-adrenoceptors.
Assuntos
Alcenos/uso terapêutico , Benzofuranos/uso terapêutico , Dor/tratamento farmacológico , Primulaceae , Alcenos/farmacologia , Animais , Benzofuranos/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , Óxido Nítrico/fisiologia , Dor/metabolismo , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Casca de Planta/fisiologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores Adrenérgicos alfa/fisiologia , Receptores de Serotonina/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
A mixture of triterpenes named lupeol (1), alpha-amyrin (2), beta-amyrin (3), and beta-sitosterol (4) has been isolated from the hexane fraction of Matayba elaeagnoides. In addition, scopoletin (5), umbelliferone (6), 3beta-O-D-glycopyranosyl-sitosterol (7) and betulin (8) were isolated from the chloroform fraction. All the structures were identified by spectroscopic techniques in accordance with literature data. The extracts (hydroalcoholic and methanolic) and some fractions (hexane, chloroform, ethyl acetate and butanol) exerted promising antinociceptive effects in mice. In addition, we have tested the pure compound betulin (8). When analyzed against induced pain using the writhing test (3-10 mg kg(-1), i.p.), betulin showed a dose-dependent effect with a calculated ID50 value of 7.74 (6.53-9.17) mg kg(-1) [17.5 (14.7-20.7) micromol kg(-1)] and a maximal inhibition (MI) of 58.3% in relation to the control group. When evaluated in the formalin test (3-10 mg kg(-1), i.p.), this compound inhibited both phases of pain (neurogenic and inflammatory pain), with calculated ID50 values of 18.3 (17.7-18.9) and 8.3 (7.7-8.9) mg kg(-1) [41.5 (38.4-42.7) and 18.8 (17.6-19.9) micromol kg(-1)] and maximal inhibition of 40.8 and 64.39% for the first and second phases, respectively. Using the same models, this compound was several times more active than two clinically used drugs, namely aspirin and paracetamol, suggesting that its main active principle is related to the antinociceptive effect found for the chloroform fraction of M. elaeagnoids barks.