Department of Biotechnology, University of Ribeirão Preto (UNAERP), São Paulo, Brazil.
Epilepsy Behav. 2011 Mar;20(3):441-6. doi: 10.1016/j.yebeh.2010.12.037. Epub 2011 Feb 1.
Neural mechanisms underlying the onset and maintenance of epileptic seizures involve alterations in inhibitory and/or excitatory neurotransmitter pathways. Thus, the prospecting of novel molecules from natural products that target both inhibition and excitation systems has deserved interest in the rational design of new anticonvulsants. We isolated the alkaloids (+)-erythravine and (+)-11-α-hydroxy-erythravine from the flowers of Erythrina mulungu and evaluated the action of these compounds against chemically induced seizures in rats. Our results showed that the administration of different doses of (+)-erythravine inhibited seizures evoked by bicuculline, pentylenetetrazole, and kainic acid at maximum of 80, 100, and 100%, respectively, whereas different doses of (+)-11-α-hydroxy-erythravine inhibited seizures at a maximum of 100% when induced by bicuculline, NMDA, and kainic acid, and, to a lesser extent, PTZ (60%). The analysis of mean latency to seizure onset of nonprotected animals, for specific doses of alkaloids, showed that (+)-erythravine increased latencies to seizures induced by bicuculline. Although (+)-erythravine exhibited very weak anticonvulsant action against seizures induced by NMDA, this alkaloid increased the latency in this assay. The increase in latency to onset of seizures promoted by (+)-11-α-hydroxy-erythravine reached a maximum of threefold in the bicuculline test. All animals were protected against death when treated with different doses of (+)-11-α-hydroxy-erythravine in the tests using the four chemical convulsants. Identical results were obtained when using (+)-erythravine in the tests of bicuculline, NMDA, and PTZ, and, to a lesser extent, kainic acid. Therefore, these data validate the anticonvulsant properties of the tested alkaloids, which is of relevance in consideration of the ethnopharmacological/biotechnological potential of E. mulungu.
癫痫发作的起始和维持的神经机制涉及抑制和/或兴奋性神经递质途径的改变。因此，从天然产物中寻找既能靶向抑制系统又能靶向兴奋系统的新型分子，这在新抗惊厥药物的合理设计中引起了关注。我们从 Erythrina mulungu 的花中分离出生物碱（+）-erythravine 和（+）-11-α-羟基-erythravine，并评估了这些化合物对大鼠化学诱导性癫痫发作的作用。我们的结果表明，不同剂量的（+）-erythravine 给药可分别抑制最大 80%、100%和 100%的荷包牡丹碱、戊四氮和海人酸诱发的癫痫发作，而不同剂量的（+）-11-α-羟基-erythravine 可抑制最大 100%的荷包牡丹碱、NMDA 和海人酸诱发的癫痫发作，对 PTZ（60%）的抑制作用较弱。对未保护动物特定剂量生物碱的癫痫发作起始平均潜伏期的分析表明，（+）-erythravine 增加了荷包牡丹碱诱导的癫痫发作潜伏期。虽然（+）-erythravine 对 NMDA 诱导的癫痫发作表现出非常弱的抗惊厥作用，但这种生物碱增加了该测定中的潜伏期。（+）-11-α-羟基-erythravine 引起的癫痫发作潜伏期增加在荷包牡丹碱试验中最大可达三倍。在使用四种化学惊厥剂的试验中，用不同剂量的（+）-11-α-羟基-erythravine 治疗所有动物均能防止死亡。在用荷包牡丹碱、NMDA 和 PTZ 进行的测试中，以及在程度较小的海人酸测试中，使用（+）-erythravine 时也获得了相同的结果。因此，这些数据验证了所测试生物碱的抗惊厥特性，这在考虑到 E. mulungu 的民族药理学/生物技术潜力时具有相关性。
