Pharmacology & Pharmacy, 2013, 4, 1-6
http://dx.doi.org/10.4236/pp.2013.47A2001 Published Online October 2013 (http://www.scirp.org/journal/pp) 1
Acute Toxicity and Antipyretic Activities of a Methanolic
Extract of Alchornea cordifolia Leaves
K. E. Effo1*, G. Kouakou-Siransy1, G. Irie-Nguessan1, R. W. Sawadogo2, I. L. Dally3, A. B. Kamenan1,
L. S. Kouakou1, J. Kablan-Brou1
1 Laboratoire de Pharmacologie et de Physiologie, UFR des Sciences Pharmaceutiques et Biologiques, Université Félix Houphouët
Boigny, Abidjan, Côte d’Ivoire; 2Laboratoire de Pharmacologie et de Toxicologie, Institut de Recherche en Sciences de la Santé
(IRSS/CNRST), Ouagadougou, Burkina Faso; 3Laboratoire de Galénique, UFR des Sciences Pharmaceutiques et Biologiques, Uni-
versité Félix Houphouët Boigny, Abidjan, Côte d’Ivoire.
Email: *effoet@yahoo.fr
Received August 9th, 2013; revised September 12th, 2013; accepted September 28th, 2013
Copyright © 2013 K. E. Effo et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Alchornea cordifolia (Euphorbiaceae) is a very prized plant among traditional healers in Africa. Its leaves are used for
its antipyretic properties in traditional areas. The aim of our study is to determine the acute toxicity and the antipyretic
activity of a methanolic extract of Alchornea cordifolia leaves. Acute toxicity was assessed by measuring mortality,
changes in body weight, spontaneous movements, and normal rectal temperature in mice. Antipyretic activity was
evaluated by brewer’s yeast-induced hyperpyrexia in rats according to Teotino method (1963). The antipyretic effect of
methanolicextract of Alchornea cordifolia leaves was compared with paracetamol (100 mg/kg bw) orally. Groups of
mice treated with doses of 6500; 3250; 1625 and 812.5mg/kg of the extr act did not show any mortality, nor sign ificant
alteration of body weight, nor alteration of spontaneous movements. However, incomplete reversed dose-dependent
hypothermic activity was observed with doses of 50.78; 101.56; 203.12; 406.25; and 812.5 mg/kg p.o. of the extract,
showing acute toxicity of this plant. In the antipyretic assay, the extract with doses of 50.78; 101.56; 203.12; 406.25;
and 812.5 mg/kg p.o. exhibited a significant dose-dependent antipyretic activity similar to paracetamol (100 mg/kg bw)
in rats. Thus Alchornea cordifolia may inhibit prostaglandins-biosynthesis from hypothalamus. Our results support
claims on its traditional uses in management of fever. However Alchornea cordifolia may aff ect hypothalamus not only
during fever but also when body temperature is normal.
Keywords: Alchornea cordifolia; Acute Toxicity; Brewer’s Yeast; Hypothermia
1. Introduction
Alchornea cordifolia (Euphorbiaceae) is a plant that is
widely used in traditional medicine in Africa, from Sene-
gal to Cameroon, as a remedy for several diseases. Its
leaves are renowned for being febrifuge [1]. Previous
studies revealed no mortality in mice in acute toxicity
tests, several pharmacological activities such as antim-
icrobial [2-4], antiameobic [5], antimalarial [6], anti-in-
flammatory [7,8], antispasmodic [9], antioxidant [10],
antidiarrheic [11], and anti-stress properties [12]. How-
ever, there is no existing pharmacological data that indi-
cated the antipyretic activity o f Alchornea cordifolia. T h u s,
the aim of our study was to determine the acute toxicity
and the antipyretic activity of the methanolic extract of
Alchornea cordifolia leaves in rats.
2. Materials and Methods
2.1. Plant Material
Fresh Alchornea cordifolia (Schum. and Thonn.) leaves
were harvested in the Floristic National Center of Abid-
jan and the collected leaves were given to the botanic
expert Prof Aké-Assi Laurent affiliated with the Univer-
sity of Cocody (Abidjan), who verified their uniformity
with the specimens previously deposited and catalogued
in the herbarium of the Floristic National Center of Abid-
jan. The leaves were collected and dried in darkness in a
25˚C air-conditioned room
2.2. Experimental Animals
Mice (Mus musculus) (15 - 34 g) and rats (Rattus
norvegicus) (weighing 150 - 286 g) were purchased from
*Corresponding author.
Copyright © 2013 SciRes. PP
Acute Toxicity and Antipyretic Activities of a Methanolic Extract of Alchornea cordifolia Leaves
2
Department of Nutrition and Pharmacology of the Uni-
versity of Cocody (Abidjan, Côte d’Ivoire). The animals
were then bred at the Department of Pharmacology of the
faculty of pharmacy of the University of Cocody. All
animals were kept in the room maintained under envi-
ronmentally controlled conditions of 24˚C ± 1˚C and 12
h light - 12 h dark cycle. The animals had free access to
water and food and were acclimatized at least 1 week
before starting the experiments. The animals were cared
for and treated according to the principles of care for, and
use of, laboratory animals, formally approved by the Bo ar d
of Ethics of the Cocody University, in compliance with
the Guide for Care and Use of Laboratory. And before
the experiments they were fasted overnight with water ad
libitum.
2.3. Chemicals
Metha nol (Si g m a ), so di um car b oxy -m e thyl -c el lul o se (CMC)
Sigma (France). Paracetamol: (Doliprane 100 mgpoudre-
pour solution buvable) (Sanofi Aventis), brewer’s yeast
Arkogélules (Arkopharma) were used in this study.
2.4. Methanolic Extract
The fine powder (200 g) of dried leaves were macerated
for 24 h at room temperature in 700 ml of methanol. The
methanolic extract obtained were dried in a rotavapor
(Büchi R180) and conserved at 4˚C, and aliquo ts of dried
powder were used for pharmacological studies after sus-
pending in 2% CM C.
For acute toxicity test, the stock solution was concen-
trated at 650 mg/ml. Three other ranges of concentration
were prepared from this stock solution by successive
dilutions in 1/2 (325 mg/ml, 162.5 mg/ml, and 81.25
mg/ml).
We used successively for th e hypothermic activity and
antipyretic activity, solutions concentrated at 81.25 mg/ml,
40.62 mg/ml, 20.31 mg/ml, 10.15 mg/ml and 5.07 mg/ml
2.5. Acute Toxicity Test
Mortality, body weight changes and spontaneous motor
activity were assessed in mice and hypothermic activity
in rats.
2.6. Spontaneous Motor Activity (SMA)
A multi-counter activity cage, Letica activity cages (LE
886) connected to AM1051 (Benwick electronics) data
logger were used for this study. The AM1051 data logger
is provided with two layers of infrared sensor placed
horizontally to monitor the rearing, mobile and static
activities, as well as the active and mobile times. Mice
were singly placed in each cage and activity was auto-
matically recorded by the instrument for 5 min. Each
mouse was used only once. The extracts (50.78; 101.56;
203.12; 406.25; and 812.5 mg/kg p.o.) were adminis-
trated to five groups of mice (n = 6) and control group
received CMC. SMA measurements started one hour after
the administration of the extract and the fourth hour and
subsequently every two days for 14 day s after treatment.
2.7. Effect on Normal Body Temperature
(Hypothermic Activity)
Rats weighing 150 - 286 g were divided into six groups
of six animals. Initial rectal temperatures were recorded
using a 12 channel electric thermometer (LETICA Scien-
tific instruments), model 812 RS, PANLAB s. L, Barce-
lona. Then extract (50.78 mg/kg; 101.56 mg/kg; 203.12
mg/kg; 406.25 mg/kg; 812.5 mg/kg) was given orally.
Temperature changes in body temperature values before
and after drug administration were recorded.
2.8. Brewer’s Yeast-Induced Hyperthermia in
Rats
Rats weighing 180 - 220 g were divided into six groups
of six animals. Initial rectal temperatures were recorded
using a 12 channel electric thermometer (LETICA scien-
tific instrument), model 812 RS, PANLAB s. L, Barce-
lona. Hyperthermia was induced in rats according to the
method of Teotino et al. [8] by subcutaneous injection of
1 ml/100g b ody weigh t of 20% brewer’s yeast. When the
temperature was at a peak, 18 h after yeast injection, only
rats which developed satisfactory pyrexia (0.6˚C or more
increase in rectal temperature) were used. Then extract
(50.78 mg/kg; 101.56 mg/kg; 203.12 mg/kg; 406.25 mg/kg;
812.5 mg/kg) was given orally 24 h after yeast injection.
Paracetamol (100 mg/kg, p.o.) served as the reference
drug for comparing the antipyretic action of extract and
the rectal temperatures of animals were recorded at 1h
interval for 4 h following drug treatment.
The results are expressed as percentage [13,14]:

Percent reduction
y east-induced pyrexiapost-treatment tem perature10 0
Yeast-induced py rexia

2.9. Statistical Analysis
The results are expressed as mean value ± S.E.M. Fried-
man’s test was applied to the results. Mean values were
considered significantly different when P < 0.05.
3. Results
3.1. Acute Toxicity
Mortality and body changes weight
No death was observed nor a significant changes in
Copyright © 2013 SciRes. PP
Acute Toxicity and Antipyretic Activities of a Methanolic Extract of Alchornea cordifolia Leaves
Copyright © 2013 SciRes. PP
3
weight (Table 1). administered at 812.5 mg/kg to the rat presented an anti-
pyretic effect superposable to that of the paracetamol
administered at 100 mg/kg. The doses of 203.125 mg/kg,
406.25 mg/kg presented also a statistically significant
antipyretic activity (p < 5%).The antipyretic effect is
totally reversed after 4 hours.
Spontaneous motor activity
After a two-week observation, the methanolic extract
from Alchornea cordifolia engendered no sign ificant mo di -
fication of spontaneous motor activity.
Effect on normal body temperature
The doses of 203.125 mg/kg, 406.25 mg/kg and 812.5
mg/kg, presented hypothermic activity (p < 5%). The
methanolic extract of Alchornea cordifolia causes a hy-
pothermia that is not totally reversed at the end of a
four-hour time (Figure 1).
Figure 3 shows the percentage of hyperthermia inhibi-
tion after two hours. We noted a reduction of the hyper-
thermia upper to 80% with 203.125 mg/kg, 406.25 mg/kg
and 812.5 mg/kg. In doses lower than 203.125 mg/kg, we
noted a percentage of reduction lower than 50%.
4. Discussion
3.2. Antipyretic Activity
Figure 2 show the antipyretic activity. During four (04)
hours, the methanolic extract of Alchornea cordifolia Alchornea cordifolia is a plant which is very currently
used in traditional medicine for the treatment of several
Table 1. Mortality and body changes weight.
Substance mice number at the beginning mice number at the end Average initial weight (g) Average weight at the end (g)
CMC 2% 8 8 22.4 24.5
MEAC: 81.25 mg/kg 8 8 22.2 22.4
MEAC: 162.5 mg/kg 8 8 22.2 23.7
MEAC: 325 mg/kg 8 8 22.3 22.3
MEAC: 6500 mg/kg 8 8 22.2 23.6
Values rep resent the average ev olution of the number of mice an d the average o f weight. Number o f animals used ( n = 8). *p < 0.005 compared to control by
Friedman’s te s t. *: P < 0.05: significantly diffe r ent compared t o control (CMC 2%).
33.5
34
34.5
35
35.5
36
36.5
37
37.5
T0h T1h T2h T3h T4h
Rectal temperature (°C)
Time interval
CMC 2%MEAC: 50.78 mg/kgMEAC: 101.56 mg/kg
MEAC: 203.12 mg/kgMEAC: 406.25 mg/kgMEAC: 812.5 mg/kg
*
*
*
**
*
*
***
MEAC: Methanolic extract of Alchornea cordifolia; CMC: carboxyméthylcellulose Curves represent the
average evo lutio n of the r ectal temper atur e in ti me. Number o f animals used (n = 6 ). *p < 0.005 compared
to control by Friedman’s test. *: P < 0.05: significantly different compared to control (CMC 2%).
Figure 1. Hypothermic activity of methanolicextract of Alchornea cordifolia.
Acute Toxicity and Antipyretic Activities of a Methanolic Extract of Alchornea cordifolia Leaves
4
33.5
34
34.5
35
35.5
36
36.5
37
37.5
T-16hT0h T1hT2h T3hT4h
Rectal temperature (°C)
Time interval
CMC 2%MEAC: 50.78 mg/kgMEAC: 101.56 mg/kg
MEAC: 203.12 mg/kgMEAC: 406.25 mg/kgMEAC: 812.5 mg/kg
Paracétamol: 100mg/kg
**
*
*
*
**
Curves r epresent the av erage evo lution o f the rect al temperat ure in t ime. Number o f animals u sed (n = 6).
*p < 0.005 compared to control by Friedman’s test. *: P < 0.05: significantly different compared to control
(CMC 2%).
Figure 2. Antipyretic activity of methanolicextract of Alchornea cordifolia and paracetamol on brewer’s yeast induced
pyrexia in rats.
0
20
40
60
80
100
120
140
160
180
Inhibition of hyperthermia (%)
Treatment
*
*
*
The result s are given are mean ± S .E.M. number of animals used (n = 6). *p < 0.005 compared to control
by Friedman’s test.
Figure 3. Inhibition of hyperthermia ofmethanolicextract of Alchornea cordifoliaand paracetamol (100 mg/kg) at two hours.
diseases associated with fever. Our works aimed to s ear ch
out a possible toxicity and an antipyretic activity. About
acute toxicity, absence of death in the present study was
also observed by Traoré [15] using 5000 mg/kg p.o. of
leaves orally and by Umukoro [12] using 4000 mg/kg
orally. The absence of modification in the spontaneous
movements shows that Alchornea cordifolia cannot mod-
ify the normal behavior in mice. However, the dose-de-
pendent hypothermia observed in the present study after
administration of Alchornea cordifolia extract showed
acute toxicity of this plant. Hypothermia indicated altera-
tion of preoptic anterior hypothalamus which is critical in
Copyright © 2013 SciRes. PP
Acute Toxicity and Antipyretic Activities of a Methanolic Extract of Alchornea cordifolia Leaves 5
the neuronal network of thermoregulation. The hypothala-
mus regulated the set point at which body temperature is
maintained. Hyperthermia inhibition observed in the pre-
sent work varies from 89% to 160%. Evolution of hyper-
thermia inhibition due to Alchornea cordifolia at 812.5
mg/kg during four hour was similar to paracetamol (100
mg/kg p.o.) with a pick at two hours (Figure 2). The
mechanism of the induced hyperthermia by brewer’s
yeast is mediated by prostaglandins biosynthesis [16,17].
Brewer’s yeast administrated through subcutaneous route,
behaves lik e an exogenous pyrogen. Thu s, it produces an
inflammatory process that according to Milton et al. [18]
and Aronoff et al. [19], leads to the biosynthesis of
chemical mediators as prostaglandins due to arachidonic
acid. Among prostaglandins, PGE2 is strongly involved
in the disturbance of the hypothalamic thermostat and so
is responsable for fever [18,19]. Thus, the antipyretic
activity of Alchornea cordifolia observed in this study
would be related to the inhibition of the production of
prostaglandins. Apart from their involvement in fever,
prostaglandins are also known for their vasodilatation
effect that generates red blotch and oedema as inflamma-
tion characteristics. Thus the hypothesis about the inhibi-
tion of the production of prostaglandins by Alchornea
cordifolia could be uphold with the works by Osabede
and Okoye [8] as well as those by Mavar-Manga et al. [7]
highlighting the protecting effect of Alchornea cordifolia
against oedema, the inflamemation model induced in
rodent.
These antipyretic property lay in the saponins contain
in Alchornea cordifolia leaves [5,9] that, according to
Gepdiremen et al. [20] are strong prostaglandin inhibi-
tors.
5. Conclusion
This antipyretic activity that is similar to paracetamol
one could partly justify the traditional use of Alchornea
cordifolia leaves against fever in the African societies.
Considering the partially reversible hypothermic effect in
a 4-hour observation time, we plan a more elaborate
study on the neurotoxicity of that plant.
6. Acknowledgments
The authors are grateful to Pr. L. Aké-Assi (Centre Na-
tional de Floristique d’Abidjan) for botanical identifica-
tion.
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