Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil; Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
Toxicol Appl Pharmacol. 2013 Nov 15;273(1):19-26. doi: 10.1016/j.taap.2013.08.015. Epub 2013 Aug 28.
Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs.
变应性哮喘是一种慢性炎症性气道疾病，其在全球的患病率不断增加。目前的哮喘治疗包括会引起明显副作用的药物，这也证明了寻找新的抗哮喘药物的必要性。小檗碱是一种双苄基异喹啉生物碱，可调节许多细胞类型的钙内流；然而，其抗过敏和潜在的毒性作用仍有待阐明。我们的目的是研究小檗碱对嗜酸性粒细胞激活和气道高反应性（AHR）的影响，并阐明其潜在的毒性作用。我们使用卵清蛋白（OVA）致敏和激发诱导的过敏性哮喘小鼠模型来评估小檗碱口服治疗的抗过敏作用。与未治疗组相比，口服小檗碱显著抑制了 OVA 激发的嗜酸性粒细胞炎症、嗜酸性粒细胞脂滴体形成和 AHR。小檗碱治疗还降低了 OVA 触发的嗜酸性粒细胞趋化因子和白细胞介素-13 的产生。维拉帕米，一种钙通道拮抗剂，具有类似的抗过敏特性，小檗碱预处理抑制了钙诱导的离体气管收缩反应，表明小檗碱发挥作用的机制是通过抑制钙依赖性反应。毒理学评价表明，与生理盐水处理的动物相比，口服给予小檗碱不会显著改变实验动物的生化、血液学、行为和物理参数。总之，小檗碱通过抑制白细胞介素-13 和嗜酸性粒细胞趋化因子以及钙内流来发挥抗过敏作用，而不会引起明显的毒性，因此具有开发抗哮喘药物的潜力。
