PHYTOTHERAPY RESEARCH, VOL.

11, 174–176 (1997)

SHORT COMMUNICATION
Antidepressant Effects of Ethanol Extract of
Areca catechu in Rodents

Ahsana Darw and Shagufta Khatoon

Pharmacology Section HEJ Research Institute of Chemistry, University of Karachi, Karachi–75270, Pakistan

We report on the antidepressant activity in the ethanol extract of Areca catechu. Antidepressant activity was
evaluated in rodents using the forced swimming and tail suspension tests. The ethanol extract (4–80 mg/kg)
caused a significant reduction in the immobility time without effecting the spontaneous motor activity. Our
findings suggest that the ethanol extract possesses antidepressant activities. © 1997 by John Wiley & Sons, Ltd.
Phytother. Res. 11, 174–176, 1997

(No. of Figures: 0. No. of Tables: 2. No. of Refs: 12.)

Keywords: Areca catechu; antidepressant activity; tail suspension test; forced swim test.

INTRODUCTION MATERIALS AND METHODS

Areca catechu (A. catechu) belongs to the family Palma- Plant material and extraction procedure. One kg dried nuts of
ceae. This chewing nut is cultivated throughout tropical Areca catechu was used to obtain the ethanol extract (ACE)
India (Satyavatia et al., 1976). Nuts contain alkaloids used in various pharmacological experiments.
namely, arecoline, arecaine, arecaidine, guvacoline, guva-
cine and traces of choline. Tannins, gallic acid, gum, oily Drugs. Clorgyline [N-methyl-N-propargyl-3 (2,4 dicholoro-
matter (Nadkarni, 1976) and a number of amino acids phenoxy) propylamine HC1] and yohimbine hydrochloride
(Satyavatia et al., 1976) are among the constituents found in (Sigma Chemical Co., USA) were dissolved in distilled
the nuts. water and ACE was suspended in 0.9% saline and
In traditional medicine it is one of the constituents in administered as a clear solution or suspension.
nervine tonic (Medicinal Plants of Nepal, 1982) and In the FST and TST tests described below animals (3–18
possesses stimulant and astringent properties. The dry nut per dose) were given either saline or test compound (i.p.:
increases salivation, lowers prespiration, sweetens the 0.2 mL/20 g, mice or 0.5 mL/100 g, rats) 1 h prior to the
breath and strengthens the gums (Nadkarni, 1976). There is experiment.
no information regarding its antidepressant properties.
Substantial efforts have been made to establish animal Forced swim test. Male Wistar rats were treated either with
models for the screening of antidepressant drugs. Of these saline or clorgyline (2.5, 5 and 10 mg/kg) or different doses
models, the forced swimming test (FST) developed by of ACE and the duration of immobility time was measured
Porsolt et al., (1977a, 1977b, 1978) has gained considerable as described earlier (Porsolt et al., 1978). Each animal was
acceptance. A similar phenomenon of immobility has also tested only once.
been described in mice which are suspended by the tail
(Steru et al., 1985). The duration of the immobility time in Tail suspension test. Male NMRI mice were treated either
both the tests were reduced after pretreatment with a wide with saline or clorgyline (4, 10, 13 and 16 mg/kg) or
variety of antidepressant agents including tricyclics, mono- different doses of ACE and the duration of immobility time
amine oxidase inhibitors (MAOI) and atypical drugs. was measured as described earlier (Steru et al., 1985).
Stress-induced conditions have led to the isolation of two
new acylsterylglucosides having antidepressant properties Yohimbine potentiation test. Potentiation of yohimbine
from the roots of Withania somnifera (Bhattacharya et al., lethality was tested using 13, 50, 100 and 200 mg/kg (10
1987). animals/dose) of ACE, as described by Quinton (1963).
In the present investigation the tail suspension test (TST),
FST, locomotion test (Svensson and Thieme, 1969) and Locomotion test. Five NMRI mice of either sex were treated
yohimbine potentiation test have been used to assess 1 h before the test with saline. Animals were placed in an
antidepressant properties in the ethanol extract of A. catechu Opto-varimex Minor (Svensson and Thieme, 1969) 15 min
(ACE). prior to observation. Ten min locomotor counts were noted
for a period of 1 h. The mean of six (10 min) readings was
noted. The same animals were treated with 10, 20 and
30 mg/kg of ACE and the observations were made as above.
w
Correspondence to: A. Dar. The counts of control and treated groups were compared.

CCC 0951–418X/97/020174–03 Accepted 15 October 1996

© 1997 by John Wiley & Sons, Ltd.
 ANTIDEPRESSANT EFFECT OF A. CATECHU 175

Statistical analysis. The F-test was applied to the results to and 21% increase in the immobility time respectively,
evaluate the significance of the differences, followed by compared with that of the control.
Duncan’s multiple range test (Milton and Tsokos, 1983). A.catechu extract significantly reduced the immobility
time at 4–80 mg/kg (Table 2). However, at 100 mg/kg there
was an 11% rise in the duration of immobility time
compared with that of the control.
RESULTS To investigate the mechanism of the antidepressant
activity of ACE, a yohimbine lethality potentiation test was
A. catechu extract was evaluated for its antidepressant performed. The mortality in the yohimbine treated mice was
activity in rodents using the following tests: TST, FST, not potentiated in the presence of ACE and no dramatic
locomotion test and potentiation of yohimbine induced change in the behaviour was observed. The locomotor
sublethality. Saline and clorgyline were included as appro- activity in mice after treatment with ACE did not differ from
priate controls. the counts obtained with control animals (2997.5 ± 680.8).
Acute toxicity was also determined and the LD50 of ACE
was found to be 600 mg/kg.
In the FST clorgyline at 2.5, 5 and 10 mg/kg caused a
DISCUSSION
17%, 42%, and 68% reduction in the immobility time,
respectively. Using the TST, clorgyline at 4, 10, 13 and
16 mg/kg caused a 18%, 32%, 63% and 92% reduction in Rodents under stress from which they cannot escape,
the immobility time, respectively. become immobile after an initial period of struggling. This
Table 1 shows the ANOVA for immobility time using the immobility signifies behavioural despair, resembling a state
FST. The reduction in the immobility time of rats treated of mental depression (Porsolt et al., 1977a; 1977b).
with 10, 13, 50, 80 and 100 mg/kg of ACE were Clorgyline, in the present study caused a dose dependent
significantly different from each other. reduction in the duration of immobility time using anti-
Table 1 also shows ANOVA for immobility time using depressant screens (TST or FST) without having significant
TST. The reduction in the immobility time of mice treated effects on the power of the movements. Similar results were
with 4, 10, 13, 50, 80 and 100 mg/kg of ACE were also obtained by previous investigators (Porsolt et al., 1977a;
significantly different from each other. 1977b; 1978; Steru et al., 1985) indicating antidepressant
Table 2 represents the means (Duncan’s multiple range properties of this drug. One of the important findings in our
test), the shortest significance range (SSRp) values and also study is that the concentration of ACE plays an important
the percent change in immobility time compared with the role in eliciting antidepressant property which was evident
control for both FST and TST. A. catechu extract lowered between 4 to 80 mg/kg and there was a reversal in the
the immobility time (FST) significantly at 10, 13 and 50 mg/ behaviour of the animal at higher concentrations. Thus
kg. However, at 80 and 100 mg/kg of ACE there was a 16% indicating that the ACE contains more than one active

Table 1. ANOVA for immobility time using forced swim and

tail suspension test
Sources of variation d.f. M.S. F-Value
FST TST FST TST FST TST
Replication 2 2 78 267.8
Treatment 5 6 9070.1 3405.6 110.3a 45.3a
Error 10 12 82.2 75.2
FST, forced swim test
TST, tail suspension test.
a
Significance at 0.01 level of probability.

Table 2. Means of Duncan’s test, SSRp values and percent change in

immobility time of forced swim and tail suspension tests
Test Control 4 10 13 50 80 100 SSRp
(ACE mg/kg) at 0.01
Mean 170s N.D. 129 86 80 198 206 8.77
FST
Percent N.D. 24↓ 49↓ 53↓ 16↑ 21↑
change
Mean 121s 98 75 47 54 113 134 7.60
TST
Percent 19↓ 38↓ 61↓ 55↓ 7↓ 11↑
change
FST, forced swim test.
TST, tail suspension test.
s, second.
Percent change, ↓/↑, Decrease/increase in the immobility time compared
with the control.
ACE, ethanol extract of A.catechu.
SSRp, shortest significant range.
N.D., not done.
176 A. DAR AND S. KHATOON

constituent and activity directed fractionation is needed to ulant activity is an underestimation and overlooks other
separate the two components. cryptic properties, such as an antidepressant activity which
The observations with the TST were largely consistent is evident only between 4–80 mg/kg concentrations.
with those obtained with the FST; however, one important Yohimbine (a2-adrenoreceptor antagonist) lethality in
pharmacological difference was that the TST appeared to be mice was unable to detect the antidepressant activity in the
more sensitive than FST. This was evident at the 10 mg/kg ACE which was identifiable by the immobility screens
concentration of the ACE where the percent reduction in the (Malick, 1981), thereby, suggesting that possibly the ACE is
immobility time was 1.5 times greater in the TST compared not interfering with the re-uptake of noradrenaline. It may
with the FST. be suggested that FST and TST are the most suitable for
The present findings also show that rodents when treated screening of antidepressant actions of the natural products.
with ACE exhibited a marked reduction in immobility time In conclusion, the A.catechu extract appears to have dual
which does not correlate with the spontaneous activity, activities which are concentration dependent. One of the
further confirming the antidepressant action of ACE. Thus activities i.e. antidepressant action is clearly reflected as a
the report in the literature that A.catechu possesses stim- reduction in the immobility time in rodents.

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