Laboratory of Immunopharmacology, Health Sciences Centre, Federal University of Paraíba, João Pessoa, PB, Brazil.
Postgraduate Program in Natural Products and Bioactive Synthetics (PgPNSB), Health Sciences Centre, Federal University of Paraíba, João Pessoa, PB, Brazil.
Inflammation. 2017 Dec;40(6):2118-2128. doi: 10.1007/s10753-017-0652-z.
Milonine is an alkaloid of Cissampelos sympodialis Eichl. (Menispermaceae), a plant used in the northeast of Brazil to treat allergies such as asthma, rhinitis, and other conditions. Previously, several alkaloids were isolated from its roots and leaves with pharmacological properties in asthma and acute inflammation models. Therefore, the aim of this study was to evaluate the milonine effect on mast cells degranulation in vivo and in vitro. Swiss mice (n = 8) were used in models of paw edema induced by carrageenan, compound 48/80, or histamine. One hour before challenge, the animals were treated with milonine (at different doses) or standard drugs and, at different time points, the edema formation was measured. In addition, other different methods, such as anaphylactic shock reaction and scratching behavior models both induced by compound 48/80, a mast cell degranulator, were used to assess milonine effect histamine release in vivo. Moreover, milonine effect on mast cell degranulation in vitro was also carried out. Firstly, it was observed that milonine significantly decreased the carrageenan edema formation only at the beginning of the reaction (i.e., up to 2 h after challenge). Furthermore, this alkaloid decreased the edema induced by compound 48/80, maintained the paw tissue integrity, without modulating histamine-induced paw edema. In anaphylactic shock reaction, milonine increased the time of animal survival when compared with compound 48/80 group. Milonine also significantly decreased the scratching behavior induced by compound 48/80 with decreasing of mast cell degranulation in vitro. Therefore, these data indicated that milonine presents anti-allergic properties by decreasing mast cell degranulation rather than acting on histamine effect.
米隆宁是青牛藤（防己科）的一种生物碱，这种植物在巴西东北部被用于治疗哮喘、鼻炎和其他疾病等过敏症。此前，从其根和叶中分离出几种具有哮喘和急性炎症模型药理作用的生物碱。因此，本研究旨在评估米隆宁对体内和体外肥大细胞脱颗粒的影响。采用角叉菜胶、复合 48/80 或组胺诱导的爪肿胀模型对瑞士小鼠（n=8）进行研究。在攻击前 1 小时，用米隆宁（不同剂量）或标准药物处理动物，并在不同时间点测量水肿形成情况。此外，还使用其他不同的方法，如过敏休克反应和由脱颗粒剂复合 48/80 引起的搔抓行为模型，评估米隆宁对体内组胺释放的影响。此外，还进行了米隆宁对体外肥大细胞脱颗粒的影响。结果表明，米隆宁仅在反应初期（即攻击后 2 小时内）显著减少角叉菜胶诱导的水肿形成。此外，该生物碱可减少由复合 48/80 引起的水肿，维持爪组织完整性，不调节组胺诱导的爪水肿。在过敏休克反应中，与复合 48/80 组相比，米隆宁增加了动物的存活时间。米隆宁还显著减少了由复合 48/80 诱导的搔抓行为，同时减少了体外肥大细胞脱颗粒。因此，这些数据表明，米隆宁通过减少肥大细胞脱颗粒而不是作用于组胺效应来表现出抗过敏特性。
