Anticonvulsant profile of the alkaloids (+)-erythravine and
(+)-11-α-hydroxy-erythravine isolated from the flowers of
Erythrina mulungu Mart ex Benth (Leguminosae–Papilionaceae)
Silmara Aparecida Faggion
a
, Alexandra Olimpio Siqueira Cunha
b
, Helene Aparecida Fachim
b
,
Amanda Salomão Gavin
a
, Wagner Ferreira dos Santos
b
,
Ana Maria Soares Pereira
a
, Renê Oliveira Beleboni
a,
⁎
a
Department of Biotechnology, University of Ribeirão Preto (UNAERP), São Paulo, Brazil
b
Department of Biology, FFCLRP, University of São Paulo (USP), São Paulo, Brazil
abstractarticle info
Article history:
Received 9 September 2010
Revised 17 November 2010
Accepted 22 December 2010
Available online 1 February 2011
Keywords:
Alkaloids
Anticonvulsants
Erythrina mulungu
(+)-erythravine
(+)-11-α-hydroxyerythravine
Natural products
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.
© 2010 Elsevier Inc. All rights reserved.
1. Introduction
Epilepsy is a set of chronic disorders that modify brain function
and are associated with the occurrence of sudden and unexpected
seizures of convulsive or nonconvulsive nature. Most epileptic
syndromes have particular neurophysiological and clinical character-
istics, the seizures being the result of abnormal, hyperactive, or
hypersynchronous neuronal discharges [1]. Moreover, neuronal
mechanisms underlying the onset and maintenance of the epilepsies
involve marked alterations in the balance between excitatory and
inhibitory neurotransmission pathways in the central nervous system
(CNS) [1,2].
In most cases, treatment of the epilepsies consists of maintaining
the patient seizure free with anticonvulsant drugs. These drugs
suppress synaptic hyperactivation by acting on ion channels,
metabolic enzymes, or neurotransmitter transporters or receptors,
the latter involving chiefly GABA and/or glutamate [3]. Despite the
considerable number of antiepileptic drugs, there is a need for novel
medicines, as not all patients with epilepsy respond satisfactorily to
the usual treatments, and also because these drugs have side effects
such as cognitive impairment, sedation, teratogenesis, and hirsutism
with chronic use [4–7]. In light of these facts, the search for novel
anticonvulsant compounds of different chemical nature and the
modification of the structure of traditional drugs may lead to the
generation of more effective and better tolerated drugs, as well as to a
better understanding of the mechanisms through which the brain
becomes epileptic [6].
Erythrina mulungu (Sin. Corallodendron mulungu (Martius) Kuntze,
Erythrina flammea Herzog, Erythrina mulungu Mart. ex Benth.) is a
deciduous tree found mainly in Brazilian cerrados and other tropical
regions [8,9].Theflowers, fruits, seeds, and bark are frequently used in
folk medicine because of their effects on the CNS; for example,
Epilepsy & Behavior 20 (2011) 441–446
⁎ Corresponding author. Unidade de Biotecnologia, Av. Costábile Romano, 2.201, Zip
Code 14096-300, Ribeirão Preto, São Paulo, Brazil.
E-mail addresses: reneusp@yahoo.com, rbeleboni@unaerp.br (R.O. Beleboni).
1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.yebeh.2010.12.037
Contents lists available at ScienceDirect
Epilepsy & Behavior
journal homepage: www.elsevier.com/locate/yebeh