Fonsêca Diogo V, Salgado Paula R R, de Carvalho Fabíola L, Salvadori Mirian Graciela S S, Penha Antônia Rosângela S, Leite Fagner C, Borges Clóvis José S, Piuvezam Marcia R, Pordeus Liana Clébia de Morais, Sousa Damião P, Almeida Reinaldo N
Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
Laboratory of Psychopharmacology, Federal University of Paraíba (UFPB), Caixa Postal 5009, CEP 58051-900, João Pessoa, PB, Brazil.
Fundam Clin Pharmacol. 2016 Feb;30(1):14-22. doi: 10.1111/fcp.12166. Epub 2015 Nov 22.
Nerolidol, an acyclic sesquiterpene found as a major constituent of several essential oils, has several pharmacological activities, but its action in pain processes has never been studied. The purpose of our research was to evaluate the antinociceptive and anti-inflammatory activities of nerolidol, as well as possible mechanisms of action, in experimental mouse models of pain. Antinociceptive activity was evaluated using the acetic acid-induced writhing test, the formalin test, and the hot-plate test. The nerolidol-treated group showed lesser acetic acid-induced abdominal contractions than the control group in all of the three doses tested (200, 300, and 400 mg/kg, p.o.). The formalin test doses of 300 and 400 mg/kg p.o. inhibited licking time, in both the first phase and the second phase. In the hot-plate test, nerolidol did not alter latency at any of the observed time points. Motor coordination, evaluated through the rotarod test, was not hindered in animals treated with nerolidol. Regarding the mechanism of action, the antinociceptive activity of nerolidol is related to the GABAergic system, and not to the opioidergic or ATP-sensitive K(+) channels. Treatment with nerolidol reduced carrageenan-induced paw edema. In the model of carrageenan-induced peritonitis, nerolidol decreased the influx of polymorphonuclear cells and also reduced levels of tumor necrosis factor (TNF-α) in peritoneal lavage. Nerolidol reduced production of interleukin 1 beta (IL-1β) in LPS-stimulated, peritoneal macrophages. Thus, these results showed that nerolidol has antinociceptive activity with possible involvement of the GABAergic system, and anti-inflammatory activity, attributed to the suppression of TNF-α and IL-1β proinflammatory cytokines.
橙花叔醇是一种无环倍半萜烯，是几种香精油的主要成分，具有多种药理活性，但它在疼痛过程中的作用从未被研究过。我们研究的目的是在实验性小鼠疼痛模型中评估橙花叔醇的抗伤害感受和抗炎活性以及可能的作用机制。使用醋酸诱导扭体试验、福尔马林试验和热板试验评估抗伤害感受活性。在所有测试的三个剂量（200、300和400毫克/千克，口服）下，橙花叔醇处理组比对照组表现出更少的醋酸诱导的腹部收缩。口服300和400毫克/千克剂量的福尔马林试验在第一阶段和第二阶段均抑制舔舐时间。在热板试验中，橙花叔醇在任何观察时间点均未改变潜伏期。通过转棒试验评估的运动协调性在接受橙花叔醇治疗的动物中未受到阻碍。关于作用机制，橙花叔醇的抗伤害感受活性与GABA能系统有关，而与阿片样物质或ATP敏感性钾通道无关。橙花叔醇治疗可减轻角叉菜胶诱导的爪部水肿。在角叉菜胶诱导的腹膜炎模型中，橙花叔醇减少多形核细胞的流入，并降低腹腔灌洗中肿瘤坏死因子（TNF-α）的水平。橙花叔醇降低脂多糖刺激的腹腔巨噬细胞中白细胞介素-1β（IL-1β）的产生。因此，这些结果表明，橙花叔醇具有抗伤害感受活性，可能涉及GABA能系统，并且具有抗炎活性，这归因于对TNF-α和IL-1β促炎细胞因子的抑制。
