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Indian Journal of Pharmacology 2000; 32: 357-360

RESEARCH PAPER

S.W. HAJARE et al.,

ANALGESIC AND ANTIPYRETIC ACTIVITIES OF DALBERGIA SISSOO LEAVES


S. W. HAJARE, SURESH CHANDRA, S. K. TANDAN, J. SARMA, J. LAL,
A. G. TELANG
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute,
Izatnagar-243 122. (U.P.)
Manuscript Received: 28.2.2000
SUMMARY

Accepted: 23.6.2000

Objective: To evaluate the analgesic and antipyretic activities of alcoholic extract of Dalbergia sissoo
leaves.
Methods: The peripheral analgesic activity of Dalbergia sissoo leaves (SLE; 100, 300 and 1000 mg/kg)
was studied using acetic acid-induced writhing in mice and by Randall-Selitto assay. The central analgesic
activity of SLE was studied using hot-plate method and tail-clip test in mice. The antipyretic activity of
SLE was studied in Brewers yeast-induced pyrexia in rats.
Results: SLE significantly decreased the writhing movements in mice in acetic acid-induced writhing
test. SLE (1000 mg/kg) significantly increased the pain threshold capacity in rats in Randall-Selitto
assay and the reaction time in hot-plate test but not in tail-clip test. It also showed significant antipyretic
activity in Brewers yeast-induced pyrexia in rats throughout the observation period of 6 h.
Conclusion: SLE may have analgesic and antipyretic activities.

KEY WORDS

Dalbergia sissoo

analgesic

antipyretic

INTRODUCTION

Dalbergia sissoo Linn (Synonyms-Shisham or


Sisam), a large deciduous tree found throughout India, has been reported in folk medicine and is used
mainly as aphrodisiac, abortifacient, expectorant,
anthelmintic and antipyretic. It is also used in conditions like emesis, ulcers, leucoderma, dysentery,
stomach troubles and skin diseases1-3. Since no information is available on analgesic and antipyretic
activities of D. sissoo leaves, the present study was
undertaken to investigate the analgesic and antipyretic activities of D. sissoo leaves.
MATERIALS AND METHODS
Preparation of D. sissoo leaf extract (SLE):
D. sissoo leaves were collected from the Indian Veterinary Research Institute Campus, Izatnagar and
were identified from Department of Botany, Bareilly
College, Bareilly.
The shade-dried leaves of D. sissoo were powdered
Correspondence: Suresh Chandra

and then extracted with 90% ethanol by heating under reflux. The ethanolic extract was concentrated
under reduced pressure to a semisolid mass and was
made free from solvent. For in vivo studies, the concentrated SLE was administered orally after suspending in normal saline. The freshly prepared solution of
SLE was used in each experiment.
Experimental animals: Colony bred Swiss mice and
Wistar rats procured from Laboratory Animal Resource Section, Indian Veterinary Research Institute,
Izatnagar were used in the study. The animals were
kept in polypropylene cages and maintained on balanced ration with free access to clean drinking water.
Analgesic activity of SLE: The peripheral analgesic activity of SLE was investigated by the acetic acidinduced writhing test4 and Randall-Selitto assay5
(Randall-Selitto apparatus, Ugo Basile, Italy) in mice
and rats, respectively. The writhing movements were
observed and counted for 20 min after acetic acid
administration. The central analgesic action of SLE

ANALGESIC AND ANTIPYRETIC ACTIVITIES OF DALBERGIA

was assessed by hot-plate6 and tail-clip test7 in mice.


SLE was used in the doses of 100, 300 and 1000
mg/kg orally in the study. Aspirin (300 mg/kg, p.o.)
and pethidine (5 mg/kg, i.p.) were also used as standard drugs for comparing analgesic effects at peripheral and central levels, respectively. Six animals were
used in each treatment group.
Antipyretic activity of SLE: The antipyretic activity
of SLE was evaluated using Brewers yeast-induced
pyrexia in rats8. Fever was induced by injecting 20
ml/kg (s.c.) of 20 per cent aqueous suspension of
Brewers yeast in normal saline below the nape of
the neck and rectal temperature was recorded by
clinical thermometer immediately before (-18 h) and
18 h after (0 h) Brewers yeast injection. Prior to the
experiment, the rats were maintained in separate
cages for 7 days and the animals with approximately
constant rectal temperature were selected for the
study. Aspirin (300 mg/kg, p.o.) was used as standard drug for comparing the antipyretic action of SLE.
Statistical analysis: The results are presented as
mean + SEM. Statistical analysis of data was performed using Students t test to study the differences amongst the means9.
RESULTS
Analgesic effect of SLE: In acetic acid-induced writhing test, SLE (100, 300 and 1000 mg/kg, p.o.) reduced
writhing counts significantly (Table 1). In Randall-Selitto
assay, SLE (100 and 300 mg/kg, p.o.) failed to alter
pain threshold capacity but increased significantly
(P<0.01) at the dose of 1000 mg/kg at 1 h. Aspirin,
significantly increased the pain threshold throughout
the observation period of 1 to 3 h (Table 1). The results
of hot-plate test indicated a significant increase in reaction time at 2 and 3 h with 1000 mg/kg SLE, whereas
reference drug pethidine hydrochloride significantly increased the reaction time at 1 and 2 h (Table 2). In tailclip test, SLE failed to alter the reaction time significantly even at the highest dose (1000 mg/kg) employed
in the present study.
Antipyretic activity of SLE: The experimental rats
showed a mean increase of about 0.86 oC in rectal temperature, 18 h after Brewers yeast injection. SLE at
100 and 300 mg/kg produced significant (P<0.05 and
P<0.01, respectively) antipyretic activity at 1 h after drug
administration, whereas SLE (1000 mg/kg) and aspirin

358

(300 mg/kg) showed significant antipyretic activity


throughout the observation period up to 6 h (Table 3).
DISCUSSION
The analgesic activity of Shisham leaf extract (SLE)
was studied for central (narcotic) and peripheral (nonnarcotic) activities. The analgesic activity of SLE
against acute inflammatory pain was moderate as
compared to potent inhibitory activity of aspirin. Aspirin and indomethacin offer relief from inflammatory
pain by suppressing the formation of pain substances
in the peripheral tissues, where prostaglandins and
bradykinin were suggested to play an important role
in the pain process10. Therefore, it is likely that SLE
might suppress the formation of these substances
or antagonize the action of these substances and
thus exerts its analgesic activity in acetic acid-induced
writhing test and in Randall-Selitto assay. In the
present study, SLE (1000 mg/kg) significantly increased the reaction time in hot-plate test, suggesting its central analgesic activity. However, it did not
show centrally-mediated analgesic effect in tail-clip
test. Presence of flavonoids were repor ted in
Dalbergia species and flavonoids are known to inhibit prostaglandin synthetase11. Since prostaglandins are involved in pain perception and are inhibited
by flavonoids, it could be suggested that reduced
availability of prostaglandins by flavonoids of SLE
might be responsible for its analgesic effect.
It is well known that most of the anti-inflammatory
analgesic drugs possess antipyretic activity. SLE revealed weak antipyretic effect at low doses (100 and
300 mg/kg) but at higher dose (1000 mg/kg), it produced marked antipyretic activity in Brewers yeastinduced febrile rats. In general, non-steroidal antiinflammatory drugs produce their antipyretic action
through inhibition of prostaglandin synthetase within
the hypothalamus 12,13. Although, there is no direct
evidence of SLE to interfere with prostaglandin synthesis in hypothalamus but it can be supported by a
related study in which D. odorifera extract was found
to inhibit prostaglandin biosynthesis14. Therefore, it
appears that antipyretic action of SLE may be related to the inhibition of prostaglandin synthesis in
hypothalamus.
In conclusion, the present study demonstrates that
SLE has marked antipyretic and moderate analgesic activities.

359

S.W. HAJARE et al.,

Table 1. Analgesic effect of SLE on acetic-acid induced writhing in mice and Randall-Selitto assay in rats.

Writhing test
Drug

Dose
(mg/kg)

Randall-Selitto assay

No. of writhings
(per 20 min)

Pressure on paw in g
0h

1h

3h

Control

51.17 3.28

49.17 6.11

54.17 7.63

56.67 6.15

SLE

100

32.33 3.67**

54.17 7.35

70.0 7.26

71.66 6.94

300

31.16 3.75**

55.00 9.83

70.83 12.66

67.50 8.48

1000

26.17 3.98***

61.67 5.43

108.33 8.33**

70.83 11.92

300

12.17 2.52***

62.50 4,22

160.83 15.15***

87.50 10.72*

Aspirin

n : six animals in each group; Values are mean + SEM. * P<0.05, ** P<0.01, *** P<0.001 when compared to control.

Table 2. Effect of SLE on thermic stimulus-induced pain (hot plate test) in mice.
Drug

Dose
(mg/kg)

Reaction time in seconds at time (h)


0

0.5

Control

8.25 1.56

8.69 1.06

8.20 0.78

12.28 1.11

11.85 + 1.46

SLE

100

9.0 1.56

7.22 0.74

9.48 0.74

14.12 1.30

11.69 1.30

300

8.39 1.17

9.16 1.25

11.17 1.81

15.90 1.05

13.86 2.07

1000
5

8.51 0.82
9.33 1.05

10.57 1.06
10.64 1.27

10.32 0.74
16.59 3.02*

17.67 1.65*
18.34 1.51**

16.96 1.65*
14.98 0.94

Pethidine

n : six animals in each group; Values are mean + SEM. * P<0.05, ** P<0.01, *** P<0.001 when compared to control.

Table 3. Effect of SLE on Brewers yeast-induced pyrexia in rats.


Drug

Dose
(mg/kg)

Rectal temperature in C at time (h)


-18a

0b

Control

36.73 0.15

37.49 0.08
(+0.76)c

37.71 0.11

37.40 0.08

37.36 0.12

37.46 0.13

SLE

100

36.43 0.11

37.33 0.08
(+0.90)c

37.18 0.15*

37.18 0.21

36.95 0.26

36.97 0.24

300

36.71 0.09

37.55 0.12
(+0.84)c

36.93 0.17**

37.08 0.18

37.06 0.24

36.95 0.24

1000

36.68 0.06

37.63 0.11
(+0.95)c

37.08 0.15**

37.11 0.07*

36.81 0.11**

36.68 0.08***

300

36.75 0.11

37.58 0.24
(+0.83)c

36.48 0.14***

36.00 0.11***

35.93 0.11*** 36.03 0.11***

Aspirin

n : six animals in each group; Values are mean + SEM. * P<0.05, ** P<0.01, *** P<0.001 when compared to control.
a : temperature just before yeast injection
b : temperature just before drug administration
c : change in temperature following yeast injection

ANALGESIC AND ANTIPYRETIC ACTIVITIES OF DALBERGIA

Pharmacol Chemother 1954;9:280-4.

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