Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Neuropharmacology. 2012 Feb;62(2):967-77. doi: 10.1016/j.neuropharm.2011.10.002. Epub 2011 Oct 20.
Natural products have been revealed as relevant sources of therapeutic agents including those for the management of pain states. In this study, the anti-nociceptive and anti-inflammatory effects of (-)-cassine, isolated from Senna spectabilis were evaluated using pharmacological, behavioural and biochemical approaches. Oral treatment with (-)-cassine (3-30 mg/kg) reduced carrageenan-induced mechanical and thermal nociception associated with the suppression of myeloperoxidase activity in the mouse paw. Moreover, (-)-cassine (1-10 μg/site) prevented mechanical hyperalgesia induced by carrageenan when given through the intraplantar (i.pl.), spinal and intracerebroventricular routes. Additionally, oral treatment with (-)-cassine (3-60 mg/kg) prevented the mechanical hyperalgesia elicited by intraplantar injection of prostaglandin E(2), complete Freund's adjuvant, interleukin-1β, interleukin-6 and keratinocyte-derived chemokine. Furthermore, (-)-cassine inhibited the mechanical nociceptive response induced by ligation of the sciatic nerve and also significantly reduced the levels of cytokines/chemokines in paw tissue following i.pl. injection of carrageenan. In addition, the anti-nociceptive and anti-inflammatory actions of (-)-cassine were associated with its ability to interact with both TRPV1 and TRPA1 receptors and by inhibiting the upregulation of cyclooxigenase-2 as well as inhibiting the phosphorylation of MAPK/ERK and the transcription factor NF-κB. It is important to highlight that oral treatment with (-)-cassine did not produce any effects related to temperature, locomotor activity or catalepsy. Altogether, the present data demonstrate that (-)-cassine has systemic, spinal and supraspinal anti-nociceptive properties when assessed in inflammatory and neuropathic pain models. These effects are associated with its ability to block several signalling pathways associated with inflammatory and nociceptive responses. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
天然产物已被证明是治疗药物的相关来源，包括用于管理疼痛状态的药物。在这项研究中，使用药理学、行为学和生物化学方法评估了从大波斯菊中分离出的 (-)-卡辛对镇痛和抗炎的作用。口服 (-)-卡辛（3-30mg/kg）可减轻角叉菜胶引起的机械性和热痛觉过敏，并抑制小鼠爪中的髓过氧化物酶活性。此外，(-)-卡辛（1-10μg/部位）通过足底内（i.pl.）、脊髓内和脑室内给药可预防角叉菜胶引起的机械性痛觉过敏。此外，口服 (-)-卡辛（3-60mg/kg）可预防前列腺素 E2、完全弗氏佐剂、白细胞介素-1β、白细胞介素-6 和角质形成细胞衍生趋化因子足底内注射引起的机械性痛觉过敏。此外，(-)-卡辛抑制坐骨神经结扎引起的机械性伤害反应，并且还显著降低角叉菜胶足底内注射后爪组织中细胞因子/趋化因子的水平。此外，(-)-卡辛的镇痛和抗炎作用与其与 TRPV1 和 TRPA1 受体相互作用的能力以及抑制环氧化酶-2 的上调和抑制 MAPK/ERK 和转录因子 NF-κB 的磷酸化有关。值得强调的是，口服 (-)-卡辛不会产生与温度、运动活动或僵住有关的任何作用。总的来说，当在炎症和神经病理性疼痛模型中评估时，(-)-卡辛具有全身、脊髓和脊髓上镇痛作用。这些作用与其阻断与炎症和伤害性反应相关的几种信号通路的能力有关。本文是题为“创伤后应激障碍”的特刊的一部分。
