Laboratório de Farmacologia Pré-Clinica, Departamento de Fisiologia, Universidade Federal de Sergipe (LAPEC/DFS/UFS), São Cristóvão, Sergipe, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2012 Mar;385(3):253-63. doi: 10.1007/s00210-011-0715-x. Epub 2011 Dec 3.
Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 μg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.
香芹酚是存在于唇形科（Lamiaceae）精油中的一种酚类单萜，如牛至属（Origanum）和百里香属（Thymus）。我们之前报道过香芹酚在各种伤害感受模型中作为一种有效的镇痛化合物是有效的，可能是通过抑制外周介质，这可能与其在体外观察到的强抗氧化作用有关。在这项研究中，通过角叉菜胶诱导的机械性痛觉过敏模型测试了香芹酚在小鼠中的抗超敏作用，并评估了其信号级联的重要介质，如肿瘤坏死因子-α（TNF-α）、前列腺素 E2（PGE2）和多巴胺的参与情况。我们还研究了香芹酚对角叉菜胶诱导胸膜炎和小鼠爪肿胀模型的抗炎作用，并观察了脂多糖（LPS）诱导的小鼠巨噬细胞中亚硝酸盐的产生。香芹酚（50 或 100mg/kg；腹腔内）全身预处理抑制了角叉菜胶和 TNF-α诱导的机械性痛觉过敏和水肿的发展，但对 PGE2 和多巴胺诱导的痛觉过敏没有影响。此外，香芹酚显著降低了胸腔灌洗液中的 TNF-α水平，并抑制了白细胞的募集，而不改变这些细胞的形态特征。香芹酚（1、10 和 100μg/mL）还显著降低了 LPS 诱导的体外亚硝酸盐产生，并且在体外对小鼠腹腔巨噬细胞没有细胞毒性。香芹酚对小鼠自发运动活动没有影响。本研究增加了香芹酚对机械性超敏反应和炎症有益作用的信息。它还表明，这种单萜类化合物可能在开发新的工具方面具有潜在的兴趣，用于管理和/或治疗疼痛状况，包括与炎症和促氧化状态相关的状况。
