Nôga Diana Aline Morais Ferreira, Brandão Luiz Eduardo Mateus, Cagni Fernanda Carvalho, Silva Delano, de Azevedo Dina Lilia Oliveira, Araújo Arrilton, Dos Santos Wagner Ferreira, Miranda Antonio, da Silva Regina Helena, Ribeiro Alessandra Mussi
Physiology Department, University Federal of Rio Grande of Norte, Natal, RN 59078-970, Brazil.
Biology Department, University of São Paulo, Ribeirao Preto, SP 14040-901, Brazil.
Toxins (Basel). 2016 Dec 23;9(1):5. doi: 10.3390/toxins9010005.
Natural products, sources of new pharmacological substances, have large chemical diversity and architectural complexity. In this context, some toxins obtained from invertebrate venoms have anticonvulsant effects. Epilepsy is a neurological disorder that affects about 65 million people worldwide, and approximately 30% of cases are resistant to pharmacological treatment. Previous studies from our group show that the denatured venom of the ant (Kempt) protects mice against bicuculline (BIC)-induced seizures and death. The aim of this study was to investigate the anticonvulsant activity of compounds isolated from venom against seizures induced by BIC in mice. Crude venom was fractionated by high-performance liquid chromatography (HPLC) resulting in six fractions referred to as DqTx1-DqTx6. A liquid chromatography-mass spectrometry (LC/MS) analysis revealed a major 431 Da compound in fractions DqTx1 and DqTx2. Fractions DqTx3 and DqTx4 showed a compound of 2451 Da and DqTx5 revealed a 2436 Da compound. Furthermore, the DqTx6 fraction exhibited a major component with a molecular weight of 13,196 Da. Each fraction (1 mg/mL) was microinjected into the lateral ventricle of mice, and the animals were observed in an open field. We did not observe behavioral alterations when the fractions were given alone. Conversely, when the fractions were microinjected 20 min prior to the administration of BIC (21.6 nM), DqTx1, DqTx4, and DqTx6 fractions increased the latency for onset of tonic-clonic seizures. Moreover, all fractions, except DqTx5, increased latency to death. The more relevant result was obtained with the DqTx6 fraction, which protected 62.5% of the animals against tonic-clonic seizures. Furthermore, this fraction protected 100% of the animals from seizure episodes followed by death. Taken together, these findings indicate that compounds from ant venom might be a potential source of new anticonvulsants molecules.
天然产物作为新的药理活性物质来源，具有丰富的化学多样性和复杂的结构。在此背景下，一些从无脊椎动物毒液中提取的毒素具有抗惊厥作用。癫痫是一种神经系统疾病，全球约有6500万人受其影响，约30%的病例对药物治疗耐药。我们小组之前的研究表明，蚂蚁（肯普特）的变性毒液可保护小鼠免受荷包牡丹碱（BIC）诱导的癫痫发作和死亡。本研究旨在探讨从蚂蚁毒液中分离的化合物对小鼠BIC诱导癫痫发作的抗惊厥活性。粗毒液通过高效液相色谱（HPLC）分离，得到六个组分，称为DqTx1 - DqTx6。液相色谱 - 质谱（LC/MS）分析显示，DqTx1和DqTx2组分中有一个主要的431 Da化合物。DqTx3和DqTx4组分显示有一个2451 Da的化合物，DqTx5组分显示有一个2436 Da的化合物。此外，DqTx6组分显示有一个分子量为13196 Da的主要成分。将每个组分（1 mg/mL）微量注射到小鼠侧脑室，并在旷场中观察动物。单独给予这些组分时，我们未观察到行为改变。相反，当在给予BIC（21.6 nM）前20分钟微量注射这些组分时，DqTx1、DqTx4和DqTx6组分延长了强直 - 阵挛性癫痫发作的起始潜伏期。此外，除DqTx5外，所有组分都延长了死亡潜伏期。DqTx6组分得到了更显著的结果，它保护了62.5%的动物免受强直 - 阵挛性癫痫发作。此外，该组分保护100%的动物免于癫痫发作后死亡。综上所述，这些发现表明蚂蚁毒液中的化合物可能是新的抗惊厥分子的潜在来源。
