Montpied Pascale, de Bock Frédéric, Rondouin Gérard, Niel Gilles, Briant Laurence, Courseau Anne-Sophie, Lerner-Natoli Mireille, Bockaert Joël
Faculté de Pharmacie, CNRS-UMR 5094, 15 Avenue Charles Flahault, 34060 Montpellier Cedex 2, France.
Brain Res Mol Brain Res. 2003 Jul 23;115(2):111-20. doi: 10.1016/s0169-328x(03)00178-5.
Caffeic acid phenethyl ester (CAPE) is an antioxidant component of propolis, a natural product secreted by honeybee. Recent literature shows that CAPE inhibits nuclear factor kappa B (NFkappaB) activation in cell lines. Since NFkappaB was shown to be a crucial factor in neuroinflammation and to be associated with some neuropathologies, CAPE might reduce these disorders in brain too and have therapeutic applications. To test this hypothesis we used a model of endotoxic insult (interferon-gamma, followed by lipopolysaccharide) on rat organotypic hippocampal cultures. Cerebral inflammatory responses were strongly inhibited by CAPE (100 microM): reductions of NFkappaB nuclear activity, tumor necrosis factor alpha and nitric oxide productions were observed. At the dose of maximal effects (100 microM), an increase of cAMP-responsive element binding protein (CREB) activity, which anti-inflammatory role is well known, was seen. We compared CAPE effects with those of other drugs: anti-inflammatory as acetyl-salicylate and dexamethasone (glucocorticoid), antioxidant as pyrrolidine dithiocarbamate, or selective permeant inhibitor of NFkappaB as SN 50 peptide. These studies lead us to conclude that CAPE presents an interesting and original neuropharmacological profile compared to these drugs and might be helpful in the prevention of neurotoxic events due to excessive inflammatory reaction in brain. CAPE interferes with several effectors of neuroinflammation that might have complementary and synergic effects and allows a rather durable control since an acute treatment at the time of endotoxin exposure allows to control inflammatory factors for over 48 h.
咖啡酸苯乙酯（CAPE）是蜂胶的一种抗氧化成分，蜂胶是蜜蜂分泌的一种天然产物。最近的文献表明，CAPE可抑制细胞系中核因子κB（NFκB）的激活。由于NFκB被证明是神经炎症中的关键因素，并与一些神经病理学相关，CAPE可能也会减轻大脑中的这些疾病并具有治疗应用。为了验证这一假设，我们在内毒素刺激（γ干扰素，随后是脂多糖）的大鼠器官型海马培养模型上进行了实验。CAPE（100微摩尔）强烈抑制了大脑的炎症反应：观察到NFκB核活性、肿瘤坏死因子α和一氧化氮生成的减少。在最大效应剂量（100微摩尔）下，观察到环磷酸腺苷反应元件结合蛋白（CREB）活性增加，其抗炎作用是众所周知的。我们将CAPE的作用与其他药物的作用进行了比较：抗炎药物如乙酰水杨酸和地塞米松（糖皮质激素）、抗氧化剂如吡咯烷二硫代氨基甲酸盐，或NFκB的选择性渗透抑制剂如SN 50肽。这些研究使我们得出结论，与这些药物相比，CAPE呈现出有趣且独特的神经药理学特征，可能有助于预防由于大脑中过度炎症反应导致的神经毒性事件。CAPE干扰了神经炎症的几种效应器，这些效应器可能具有互补和协同作用，并且由于在内毒素暴露时进行急性治疗可以控制炎症因子超过48小时，从而实现相当持久的控制。
