Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil.
Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
J Ethnopharmacol. 2014 Sep 11;155(2):1118-24. doi: 10.1016/j.jep.2014.06.041. Epub 2014 Jun 23.
Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice.
To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 μg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges.
Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3.
Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.
瓜里宁是一种双苄基异喹啉生物碱，是从肋柱花（Chondrodendron platyphyllum）中分离得到的主要成分，肋柱花在巴西民间医学中被用于治疗炎症性疾病。本研究旨在探讨瓜里宁对小鼠肥大细胞依赖性反应的作用。
为了诱导肥大细胞依赖性反应，将瑞士小鼠用卵清蛋白（OVA-12 μg/只）和 Al（OH）3 在 0.9% NaCl 溶液中皮下致敏。15 天后，通过不同途径用 OVA 对动物进行攻击。或者，向动物注射化合物 48/80 或组胺，并分析过敏反应、瘙痒、水肿和炎症介质产生等多个参数。苯海拉明、色甘酸钠和维拉帕米用作对照药物，所有治疗均在攻击前 1 小时进行。
瓜里宁预处理显著抑制了化合物 48/80 或 OVA 诱导的搔抓行为和爪水肿，其保护作用与色甘酸钠或维拉帕米相当。相比之下，瓜里宁对组胺诱导的爪水肿抑制作用较弱，而苯海拉明则完全抑制了该作用。瓜里宁和维拉帕米显著抑制了过敏原性胸膜炎引起的胸腔蛋白渗出、前列腺素 D2（PGD2）和半胱氨酰白三烯（CysLTs）的产生。此外，与维拉帕米一样，瓜里宁也抑制了化合物 48/80 或过敏原引起的过敏性休克。在体外环境中，这些治疗方法还通过 IgE 依赖性激活肥大细胞系 RBL-2H3 抑制脱颗粒以及 PGD2 和 CysLT 的产生。
瓜里宁通过与肥大细胞稳定和激活抑制相关的机制，而不是通过干扰肥大细胞产物的促炎作用，显著抑制了即刻过敏反应。这些发现与生物碱瓜里宁可能有益于治疗过敏疾病的假说一致。
