Neuropharmacology Laboratory, Institute of Biological Sciences, Department of Physiological Sciences, University of Brasília, Distrito Federal, DF, Brazil.
Mass Spectrometry Laboratory, EMBRAPA Genetic Resources and Biotechnology, Distrito Federal, DF, Brazil.
Biochem Pharmacol. 2020 Nov;181:114119. doi: 10.1016/j.bcp.2020.114119. Epub 2020 Jun 23.
Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, and also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters. Additionally, we also evaluated the electroencephalographic (EEG) profile in the PTZ-induced acute seizures in animals treated with Neuropolybin, and potential adverse effects of both peptides in general spontaneous activity (Open Field analysis). Interestingly, Ppnp7 and Neuropolybin showed a noteworthy antiseizure effect in rats and mice, respectively. Curves of protection against the maximum seizure were obtained for both peptides, and EEG records demonstrated that Neuropolybin protected 80% of animals from tonic-clonic seizures when applied with a dose of 3 nmol (an approximate Ppnp7 ED found in rats). Neuropolybin and Ppnp7 did not cause changes in the general spontaneous activity of the animals in any of the doses evaluated. Therefore, this study demonstrated how compounds isolated from wasps' venom may be essential resources in the search for new drugs, and can also be considered valuable therapeutic and biotechnological tools for the study and future treatment of epileptic disorders.
癫痫是最严重的神经障碍之一，由于成本高和副作用大，其治疗仍然是一个挑战。从节肢动物毒液中提取的生物活性分子被认为是一种有前途的治疗方法，因为这些化合物以其高度选择性和高效性而闻名。本研究的目的是鉴定和表征从社交黄蜂 Polybia paulista 的毒液中提取的肽 Ppnp7 的潜在抗癫痫作用，以及生物灵感肽 Neuropolybin 在相同参数下的作用。此外，我们还评估了用 Neuropolybin 治疗的动物在 PTZ 诱导的急性癫痫发作中的脑电图 (EEG) 谱，以及这两种肽的一般自发活动（开放场分析）的潜在不良反应。有趣的是，Ppnp7 和 Neuropolybin 分别在大鼠和小鼠中表现出显著的抗癫痫作用。两种肽都获得了针对最大癫痫发作的保护曲线，EEG 记录表明，当以 3nmol 的剂量应用时，Neuropolybin 可保护 80%的动物免受强直-阵挛性癫痫发作（在大鼠中发现的近似 Ppnp7 ED）。在评估的任何剂量下，Neuropolybin 和 Ppnp7 都不会引起动物一般自发活动的变化。因此，本研究表明，从黄蜂毒液中分离的化合物可能是寻找新药的重要资源，并且还可以被认为是研究和未来治疗癫痫障碍的有价值的治疗和生物技术工具。
