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Fitoterapia 75 (2004) 309–314

Anticonvulsant activity of Mimosa pudica


decoction
E. Ngo Buma,*, D.L. Dawacka, M. Schmutzb, A. Rakotonirinac,
S.V. Rakotonirinac, C. Portetb, A. Jekerb, H.-R. Olpeb,
P. Herrlingb
a
´
Departement des Sciences Biologiques, Faculte´ des Sciences,
Universite´ de Ngaoundere
´ ´ B.P. 454 Ngaoundere,
´ ´ BP, Cameroon
b
Novartis Pharma Ltd., Research, CH-4002 Basel, Switzerland
c
´
Departement de Biologie et Physiologie Animale, Faculte´ des Sciences,
B.P. 812 Universite´ de Yaounde,
´ Cameroon

Received 1 July 2003; accepted in revised form 20 January 2004

Abstract

The decoction of Mimosa pudica leaves given intraperitoneally at dose of 1000–4000 mgy
kg protected mice against pentylentetrazol and strychnine-induced seizures. M. pudica had
no effect against picrotoxin-induced seizures It also antagonized N-methyl-D-aspartate-
induced turning behavior. These properties could explain its use in African traditional
medicine.
䊚 2004 Elsevier B.V. All rights reserved.

Keywords: Mimosa pudica; Anticonvulsant; Sedative; Seizures

1. Introduction

Mimosa pudica L. (Mimosaceae) is a common plant in moist waste ground,


lawns, open plantations and weedy thickets. It is native from Middle America and
now widely distributed in all tropical areas w1–3x. In many countries, extracts of M.
pudica are used in the treatment of headache, migraine, insomnia, diarrhea, dysentery,
*Corresponding author. Tel.: q237-797-5997; fax: q237-2252599.
E-mail address: eli_bum@yahoo.fr (E. Ngo Bum).

0367-326X/04/$ - see front matter 䊚 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.fitote.2004.01.012
310 E. Ngo Bum et al. / Fitoterapia 75 (2004) 309–314

fever, piles, fistula w4,5x. The phytochemical characterization of M. pudica shows


the presence of tannins, steroids, alkaloids, triterpenes and flavonoides glycosides,
C-glycosylflavones w4x. Some studies have reported hyperglycemic effects of the
leaves of M. pudica w4,5x. Only few pharmacological studies have been reported on
this plant, claimed in traditional medicine to treat many diseases related to the
nervous system. Thus, the aim of the present study is to evaluate the effect of M.
pudica in this system and particularly its anticonvulsant activity.

2. Experimental

2.1. Plant material

M. pudica dried leaves (2.4 g), collected in the campus of the University of
´ ´ Cameroon, were boiled in 30 ml distilled water for 30 min. The
Ngaoundere,
supernatant was collected, filtered and evaporated to 6 ml corresponding to a
concentration of 0.4 gyml (yield: 5%).

2.2. Animals

Male Swiss mice (20–25 g) were used for this study. The animals were housed
in standard environmental conditions and fed with food and water ad libitum.

2.3. Anticonvulsant tests

2.3.1. Strychnine (STR) test


Covulsions followed by death were induced in mice by the i.p. injection of 2.5
mgykg strychnine nitrate. A protective effect of the extract given at doses ranging
from 500 to 4000 mgykg i.p. 1 h prior to STR was recorded and compared to the
control group and group received 3 mgykg of clonazepam (clonaz). The animals
that survived more than 10 min were regarded as protected w6x.

2.3.2. Pentylenetetrazol (PTZ) test


Clonic seizures were induced in male mice by the i.p. injection of 70 mgykg
PTZ. Animals that did not exhibit seizures within the 10 min observation period
were regarded as protected. Clonazepam 0.1 mgykg was used as a reference
compound w7,8x.

2.3.3. N-methyl-D-aspartate (NMDA) test


Mice were injected subcutaneously with NMDA, 75 mgykg, 1 h after administra-
tion of the extract. They were observed for 30 min. Animals that did not exhibit
turning behavior within the 30 min observation period were regarded as protected.
Turning behavior was characterized by two consecutive 3608 cycles fulfilled by the
animal. For the non-protected animals, the onset time of this behavior was recorded.
CGP 37849, 3 mgykg, a well-known NMDA antagonist was used as a reference
standard w7,8x.
E. Ngo Bum et al. / Fitoterapia 75 (2004) 309–314 311

Fig. 1. Effect of M. pudica decoction on strychnine (STR) -induced tonic seizures and death in mice.
Ns8; P-0.05, **P-0.01, ***P-0.001 (Fisher exact test: two tail); CON: distilled water. Clonaz:
Clonazepam (3 mgykg; i.p.).

2.3.4. Picrotoxin (PIC) test


Clonic seizures were induced in male mice by the i.p. injection of 7.5 mgykg
PIC w6x. A protective effect of the extract against PIC-induced clonic seizures was
recorded in mgykg Clonazepam, 0.4 mgykg, was used as positive control.

2.4. Analysis of data

The ED50 values (dose at which 50% of the animals are protected) were
determined from the logarithmic dose response curves. The latency of the onset of
seizures was evaluated by using the correction for Multiple t-test by Bonferroni
method. The Fisher exact test (two-tail) was used to compare percentage of
protected mice in each case.

2.5. Chemicals

PTZ, PIC, NMDA, STR and clonazepam were from Sigma Chemical, USA. CGP
37849 from Novartis, Basle, Switzerland.

3. Results

Decoction of M. pudica dose-dependently protected mice against STR-induced


seizures and exitus. The percentages of protection were 12.5% and 100% at doses
of 500 mgykg and 4000 mgykg i.p., respectively (Fig. 1). The ED50 was determined
312 E. Ngo Bum et al. / Fitoterapia 75 (2004) 309–314

Fig. 2. Effect of M. pudica decoction on pentylenetetrazolo (PTZ)-induced clonic seizures in mice. Ns


8; P-0.05, **P-0.01, ***P-0.001 (Fisher exact test: two tail); CON: distilled water. Clonaz: Clon-
azepam (0.1 mgykg; i.p.).

as 1341 (855–2104) mgykg i.p. Moreover, the decoction of M. pudica dose-


dependently protected animals against clonic seizures induced by PTZ (Fig. 2). At
the dose of 500 mgykg i.p., the decoction protected 12.5% of mice against seizures.
The dose of 4000 mgykg provided protection to 80% of mice. The ED50 was
determined as 1471 (1009–2146) mgykg i.p. On the contrary, the decoction did not
possess a significant effect against PIC-induced seizure.
The turning behavior induced by NMDA (75 mgykg) was antagonized by the
dose of 3 mgykg i.p. of CGP 37849, a well known NMDA antagonist. The decoction
prevents mice from turning in a dose-dependent fashion: 12.5%, 37.5% and 62.5%
of the animals did not show turning behavior at the doses of 1000 mgykg, 2000
mgykg and 4000 mgykg i.p., respectively (Fig. 3). In non-protected animals, the
time to the onset of the turning behavior was delayed significantly only at dose of
2000 and 4000 mgykg (control group: 8.4"3.4 min; decoction 2000 mgykg:
15"4.6 min; 4000 mgykg: 17.5"4.9 min).

4. Discussion

The decoction of M. pudica antagonized chemically-induced seizures in mice. It


significantly protected mice against STR and PTZ -induced seizures with an ED50
of 950 mgykg and 1200 mgykg i.p., respectively. Turning behavior induced by
NMDA in mice was dose-dependently antagonized by the extract of M. pudica. On
the contrary, the decoction of M. pudica had no effect on PIC-induced seizures.
E. Ngo Bum et al. / Fitoterapia 75 (2004) 309–314 313

Fig. 3. Effect of M. pudica decoction on N-methyl-D-aspartate (NMDA)-induced turning behavior in


mice. Ns8; P-0.05, **P-0.01, ***P-0.001 (Fisher exact test: two tail); CON: distilled water; CGPs
CGP37849 (3 mgykg).

Among the tests used, the PTZ test is of predictive relevance regarding the clinical
spectrum of activity of experimental compounds w9,10x. Since the PTZ test is
assumed to identify anticonvulsant drugs effective against generalized clonic seizures
w9–12x, the effect of the extract of M. pudica in this test could therefore suggest
anticonvulsant efficacy against the above-mentioned seizures type in man. Antago-
nism of PTZ-induced seizures suggests that the extract of M. pudica might have
effects on GABA-ergic neurotransmission as PTZ has been shown to interact with
the GABA neurotransmitter w10,11,13x. These effects, however, do not seem to be
related to the picrotoxin site of the GABA receptor complex w11x because PIC-
induced seizures were not antagonized. The inhibition by M. pudica of STR-induced
seizures and NMDA-induced turning behavior suggests that additional mechanisms
might be involved. Inhibition of STR-induced seizures suggests interaction through
glycine receptors w14x while antagonism of NMDA-induced turning behavior
suggests interaction through NMDA receptors w7,8x. The multiplicity of putative
mechanisms of action and the broad spectrum of anticonvulsant activity of M.
pudica might be due to the presence of different active components interacting
simultaneously. Although, further pharmacological and chemical studies are well
envisaged, the results of this study confirm the presence of sedative and anticon-
vulsant properties in the decoction of M. pudica.
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