Anticonvulsant profile of the alkaloids (+)-erythravine and (+)-11-α-hydroxy-erythravine isolated from the flowers of Erythrina mulungu Mart ex Benth (Leguminosae–Papilionaceae)

Abstract

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.

Erythrina mulungu Alkaloids Are Potent Inhibitors of Neuronal Nicotinic Receptor Currents in Mammalian Cells

“…Aqueous alcoholic extracts of E. mulungu produce anxiolytic-like effects in rats submitted to elevated T-maze and light/dark transition tests [3], [4], as well as antinociceptive and anticonvulsant effects in mice [5], [6], raising interest in the discovery of neuroactive compounds in the plant. Three previously known and one novel erythrinian alkaloid recently isolated from the flowers of E. mulungu reproduced some of the CNS effects of the polar extracts [7]–[10]. In particular, oral administration of (+)-erythravine and (+)-11α-hydroxyerythravine induced anxiolytic-like effects comparable to that of diazepam in mice, while (+)-11α-hydroxyerysotrine was only effective in some tests [8], [9].…”

The genus Erythrina L.: A review on its alkaloids, preclinical, and clinical studies

“…Adapted from Dewick (2009) andMaier et al (1999) Flowers (Flausino, Santos, et al, 2007) 7 11α-Hydroxyerythravine E. verna (syn. E. mulungu) Flowers (Flausino, Santos, et al, 2007;Faggion et al, 2011) Flowers (Flausino, Santos, et al, 2007;Faggion et al, 2011) 30 Erythristemine E. lysistemon Flowers, pods, seeds (Amer, El-masry, et al, 1991;Juma & Majinda, 2004 to observe that oxygen atom in erythrinine (42) interacts with GLU101 and the hydroxyl group interacts with ILE125. Erythrinine (42) showed an inhibitory constant of 5.95 μmol/L with negative binding energies of 7.13 kcal/mol (Raji & Muthukumar, 2016).…”

“…Animals were treated with different concentrations of alkaloids (0.25 to 3 μg/μl) by intracerebroventricular injection. Erythravine ( 29 ) was able to inhibit seizures induced by bicuculline, pentylenetetrazol, and kainic acid, whereas 11α‐hydroxyerythravine ( 7 ) had effects against bicuculline, N‐methyl‐D‐aspartic acid, kainic acid, and pentylenetetrazole (Faggion et al, ). With the use of the same methods, the effects of erysotrine ( 26 ), isolated from flowers of E. verna (syn.…”

Mulungu – Rainforest Anxiolytic

“…Data of Dantas and coworkers (2004) showed that the crude extract of E. velutina at lower doses interferes with mnemonic process for different tasks, while at higher doses, the sedative and neuromuscular blocking actions are the main effects. Anticonvulsant profile of erythrina alkaloids was recently studied by Faggion et al (2011). They 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 (Faggion et al 2011).…”

“…Anticonvulsant profile of erythrina alkaloids was recently studied by Faggion et al (2011). They 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 (Faggion et al 2011). These 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-hydroxyerythravine inhibited seizures at a maximum of 100% when induced by bicuculline, NMDA, and kainic acid, and, to a lesser extent, pentylenetetrazole (60%).…”