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Original Paper
Med Princ Pract 2009;18:378–384
DOI: 10.1159/000226292
Anti-Inflammatory and Antinociceptive
Effects of Mitragyna speciosa Korth
Methanolic Extract
W.M. Shaik Mossadeq a, c M.R. Sulaiman a T.A. Tengku Mohamad a H.S. Chiong a
Z.A. Zakaria d M.L. Jabit e M.T.H. Baharuldin b D.A. Israf a
Departments of
a Biomedical Sciences and
b Human Anatomy, Faculty of Medicine and Health Sciences, and
c Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia,
Serdang,
d Faculty of Pharmacy, Universiti Teknologi MARA, Shah Alam, and
e Technical Services Centre, MARDI,
Kuala Lumpur, Malaysia
200 mg/kg) significantly and dose-dependently suppressed
the development of carrageenan-induced rat paw edema
(p ! 0.05). In the chronic test, however, significant reduction
in granulomatous tissue formation in rats was observed only
at the highest dose of the methanol extract of M. speciosa
(200 mg/kg, p ! 0.05). Conclusion: The present study sug-
gests the presence of potent antinociceptive and anti-in-
flammatory principles in the extract, supporting its folkloric
use for the treatment of these conditions.
Copyr ight © 2009 S. Karger AG, B asel
Introduction
Mitragyna speciosa Korth, a member of the Rubiaceae
family, is a tropical plant that is widely found in the rain-
forests of Malaysia and in the central and southern re-
gions of Thailand. The leaves of the M. speciosa Korth
tree, known as ‘biak-biak’ or ‘ketom’ in Malaysia and as
‘kratom’ in Thailand, are often chewed, smoked or made
as tea and have been traditionally used by many laborers
to increase work efficiency and tolerance of hard work
[1] .
In Malaysia’s folk medicine, the leaves are used to treat
diarrhea, fever, asthma, as cough suppressant and for
Key Words
Mitragyna speciosa ⴢ Anti-inflammatory ⴢ Antinociceptive ⴢ
Opioid system
Abstract
Objectives: To determine the anti-inflammatory and antino-
ciceptive activities of Mitragyna speciosa Korth methanol ex-
tract in rodents. Materials and Methods: Anti-inflammatory
activity was evaluated using carrageenan- induced paw ede-
ma and cotton pellet-induced granuloma tests in rats. Anti-
nociceptive activity was measured using the writhing test
and the hot plate test in mice, and the formalin test in rats.
All drugs and extracts were diluted in dH
2 O and adminis-
tered through the intraperitoneal route. Results were ana-
lyzed using one-way ANOVA followed by Dunnett’s test
for multiple comparisons among groups. Results: Results
showed that intraperitoneal administration of the extract at
doses of 100 and 200 mg/kg produced significant dose-de-
pendent activity in all of the nociceptive models evaluated
(p ! 0.05). With the formalin test, the antinociceptive activity
in mice was inhibited only at the highest dose of the extract
(200 mg/kg). The study also showed that intraperitoneal ad-
ministration of the methanol extract of M. speciosa (100 a nd
Recei ved: October 29, 2008
Revis ed: February 12, 2009
Prof. Dr. Mohd Roslan Su laiman
De partment of Biomed ical Sciences , Faculty of Medicine and Health Scienc es
Universiti Putra Ma laysia, 4 3400 Serdang, Selangor (Malaysia)
Tel. +60 3 8947 2603, Fax +60 3 8947 2585
E-Mail mrs@medic.upm.edu.my or mrs 4969@gmail.com
© 200 9 S. Karger AG, Basel
1011–7571/09/0185–0378$26.0 0/0
Accessible online at:
www.karger.com/mpp
Pharmacological Effects of Mitragyna
speciosa Korth Extract
Med Princ Pract 2009;18:378–384
379
some users, to prolong sexual intercourse. In addition, it
is also used for deworming, as cure for stomach ailments
and as a substitute for opium or morphine in the treat-
ment of drug addicts [2, 3] . Over 20 alkaloids have been
isolated from M. speciosa leaves, with mitragynine re-
ported to be the major alkaloid that is responsible for the
substance’s opioidergic effect
[4, 5] . Pharmacologically,
M. speciosa has been shown to possess antitussive, anti-
nociceptive, anti-inflammatory and antidiarrheal prop-
erties
[1, 6 –8] . Despite the reported antinociceptive and
anti-inflammatory activities of M. speciosa methanol ex-
tract (MSM), previous studies focused on the activities of
its alkaloids. Therefore, the aim of the present study was
to investigate the medicinal properties of MSM with re-
gard to its anti-inf lammatory and antinociceptive effects,
so as to provide some pharmacological evidences for its
folkloric uses.
Materials and Methods
Plant Material
The fresh mature leaves of M. speciosa were collected from
undisclosed locations in Selangor and Perlis, Ma laysia. The leaves
were identified and authenticated taxonomically by a botanist,
Ms. Radhiah Zakaria, at the Herbarium Laboratory, Faculty of
Forestry, Universiti Putra Malaysia (UPM), Serdang, Selangor,
where a voucher specimen (ALS 001) was deposited for future ref-
erence.
Preparation of the Extract
MSM was prepared as previously described
[9] . Brief ly, the
leaves (1,000 g) were dried at room temperature for 10 days, pul-
verized into a coarse dry powder ( ! 1 mm from our observation)
and extracted wit h 95% methanol in the ratio of 1:
10 (w/v) by cold
maceration for 72 h. The extract was evaporated to a dark brown
semisolid mass (yield 12%, w/w) under reduced pressure and kept
at –20
° C prior to use.
Phytochemical Analysis
Phytochemical screening of the MSM was performed to detec t
the presence of different classes of constituents, such as alkaloids,
flavonoids, saponins , steroids and triterpenoids , using the follow-
ing reagents and chemicals: alkaloids with Mayer and Dragen-
dorff ’s reagents, flavonoids with NaCl and HCl, tannins with 1%
gelatin and 10% NaCl solutions, saponins with frothing test and
finally, steroids and triterpenoids with Liebermann-Burchard
test.
A n i m a l s
Adult male Sprague-Dawley rats (150 –200 g) and ma le Balb C
mice (20–30 g) were used throughout these experiments. The an-
imals were maintained in a room with a 12-hour light-dark cycle
for at least 7 days before the experiment to allow acclimatization.
The animals were provided with food and water ad libitum. All
experiments were performed according to the Ethical Guidelines
for Investigations of Experimental Pain in Conscious Animals
[10] and approved by the Ethics Committee on Animal Experi-
mentation, Faculty of Medicine and Health Sciences, UPM.
W r i t h i n g Te s t
The test was performed according to Zakaria et al.
[11] , with
slight modifications
[12] . Sixty mice which were equally divided
into six groups (n = 10) were intraperitoneally (i.p.) pretreated
with MSM (50, 100, 200 mg/kg), 0.9% NaCl (control), acetylsali-
cylic acid (ASA, 100 mg /kg) or morphine (5 mg/kg ). In an at tempt
to investigate the participation of the opioid system in the antino-
ciceptive activity of this plant, two separate groups of mice con-
sisting of 10 mice per group were pretreated with the nonselective
opioid receptor antagonist naloxone (5 mg/kg, i.p.), which was
injected 10 min before the administration of the extract (200 mg/
kg, i.p.) or morphine (5 mg/kg, i.p.). After 30 min, 0.6% (v/v) solu-
tion of acetic acid was injected i.p. (10 ml/kg). The number of ab-
dominal constrictions together with the stretching of one or both
hind legs occurring between 5 and 30 min after acetic acid injec-
tion was recorded.
F o r m a l i n T e s t
This procedure was essentially simila r to that described previ-
ously by Zakaria et al.
[11] . Sixt y rats were equally divided into six
gr oups (n = 10). In thi s mo del, for mal in (2.5%, 50 l) was injected
via the intraplantar route into the right hind paw of rats 30 min
after the i.p. administration of 0.9% NaCl (10 ml/kg, control),
MSM (50, 100, 200 mg/kg), ASA (100 mg/ kg), or morphine (5 mg/
kg). The amount of time the animal spent licking or biting the
injected paw was measured between 0 and 5 min (phase 1, neuro-
genic) and 15–30 min (phase 2, inflammatory) after the injection
of formalin.
Hot Plate Test
The test was performed as previously described
[11] . In this
mo de l, 6 0 m ic e w er e e qu al ly d iv id ed in to si x g r oup s ( n = 10). T hi r-
ty minutes after pretreatment with either 0.9% NaCl (control),
MSM (50, 100, 200 mg/kg, i.p.), ASA (100 mg/kg), and morphine
(5 mg/kg), the mice were placed on a heated metal plate (Ugo
Basile, model 7280) maintained at 53 8 1 ° C and the response la-
tency for nociceptive behavior, e.g. shaking, licking the paw or
jumping, was recorded. Mice were removed from the hot plate
immediately after the response. Response latencies were mea-
sured at 0-, 30-, 60-, 120-, 180-, and 240-min intervals after sub-
stance administration, with a cutoff time of 20 s to avoid tissue
injury. In order to investigate the participation of the opioid sys-
tem in the analgesic property of this plant, two separate groups of
mice consisting of 10 mice per group were pretreated with the
nonselective opioid receptor antagonist naloxone (5 mg/kg, i.p.),
which was injected 10 min before the administration of the ex-
tract (200 mg/kg, i.p.) or morphine (5 mg/kg, i.p.) and the exper-
iment was repeated.
Carrageenan-Induced Paw Edema Test
The carrageenan-induced rat paw edema was assessed by the
method described by Loro et al.
[13] . Paw edema was measured
with a plethysmometer (model 7140, Ugo Basile, Italy). The basal
volume of the right hind paw was determined before administra-
tion of any drug. Eight animals per group were pretreated with
MSM (50, 100 and 200 mg/kg, i.p.). Thirty minutes later, edema
Shaik Mossadeq et al.
Med Princ Pract 2009;18:378–384
380
was induced with 0.1 ml of 1% (w/v) solution of carrageenan, in-
jected into the subplantar region of the rat hind paw. Control an-
imals received 0.9% NaCl (10 ml/kg), whereas positive control
animals received ASA (100 mg/kg) under the same experimental
conditions. The volumes of the injected paws were measured im-
mediately after injection (0 h) and then every hour until 5 h after
induction of edema. The results are presented as the paw volume
variation in relation to basal values.
C o t t o n P e l l e t - I n d u c e d G r a n u l o m a T e s t
The met hod of Okoli et al.
[14] wa s e mp loy ed , w it h s li gh t mo d-
ifications. Forty rats were equally div ided into five groups (n = 8).
On day 1, the rats were pretreated with MSM (50, 100 and 200
mg/kg, i.p.). Control animals received either 0.9% NaCl or equal
volume of ASA (100 mg/kg). Thirty minutes after pretreatment,
a sterilized cotton pellet (30 8 1 mg) was subcutaneously intro-
duced in the dorsum of rats anesthetized with Avertin (10 ml/kg,
i.p.). The rats were treated with a single injection of ASA, 0.9%
NaCl or MSM (50, 100 and 200 mg/kg) daily for 7 consecutive
days. On day 8, the animals were sacrificed, the pellets dissected
out and granulomas dried at 60
° C overnight to determine the fi-
nal dry weight. The difference between the initial (30 mg) and
final dry mass was considered as t he weight of the granulomatous
tissues produced.
Statistical Analysis
The results were expressed as mean 8 SEM and analyzed us-
ing one-way A NOVA followed by Du nnett’s test for mu ltiple com-
parisons among groups. Values with p ! 0.05 were considered to
be statistically significant.
R e s u l t s
Phytochemical Analysis
A phytochemical screening of MSM indicated the
presence of the following secondary metabolites: alka-
loids and flavonoids in high concentration, saponins in
moderate concentration, while tannins and sterols were
detected in a low concentration. The extract, however,
was devoid of triterpenes.
Effect of MSM on Acetic Acid-Induced Writhing
The results of the acetic acid-induced writhing test
in mice are given in table 1 . At doses of 100 and 200 mg/
kg i.p., MSM inhibited the writhing responses of mice
caused by the intraperitoneal administration of acetic
acid. The maximal inhibition of the writhing response
was 52.3% with the dose of 200 mg/kg, slightly lower
compared to inhibition by ASA (55.5%) at a dose of 100
mg/kg.
Effect of MSM on the Formalin Test
MSM (200 mg/kg) and morphine significantly inhib-
ited both phases of the formalin test showing a pain in-
hibition of 37.4 and 36.0% in the early phase (0–5 min)
and 46.3 and 53.9% in the late phase (15–60 min), respec-
tively. In contrast, ASA inhibited only the second phase
of the formalin response ( table 2 ).
Effect of MSM in the Hot Plate Test
Morphine and MSM (200 mg/kg) caused a significant
increase in the response latency time to thermal stimula-
tion in mice ( table 3 ). This effect started 30 min after
treatment and persisted throughout the 240-min dura-
tion of the experiment.
Tab le 1. Effect of MSM on acetic acid-induced abdominal writh-
ing test in mice
Group Dose,
mg/kg, i.p.
Writhings Inhibi-
tion, %
Control (NaCl 10 ml/kg, i.p.) 134.7812.3 –
MSM 50.0 105.6812.6 21.6
100.0 81.387.9*39.6
200.0 64.2811.3*52.3
ASA 100.0 59.9810.8*55.5
Morphine
Morphine+naloxone
MSM+naloxone
5
5+5
200+5
25.989.1
53.7810.51
77.283.9
80.7
60.1
42.0
Values are mean 8 SEM (n = 10). * p < 0.05 significantly dif-
ferent f rom c ontrol (ANOVA foll owed by Du nnett ’s tes t). Cont rol
(13 4.7 8 38.75).
Tab le 2. Effect of MSM on formalin-induced pain in mice
Treatment Total time spent licking, s
0–5 min inhibi-
tion, %
15–30 min inhibi-
tion, %
Control
(NaCl 10 ml/kg, i.p.) 64.686.5 – 205.5812.8 –
MSM, mg/kg, i.p.
50.0 57.685.4 10.8 171.3820.3 16.6
100.0 57.685.5 10.8 131.0819.7*36.2
200.0 40.484.6*37.4 109.0814.1*46.3
ASA, mg/kg, i.p.
100.0 54.084.9 16.4 144.9822.4*29.5
Morphine, mg/kg, i.p.
5.0 41.483.51*36.0 94.8815.7*53.9
Values are mean 8 SEM in seconds (n = 10). * p < 0.05 com-
pared to the control group (ANOVA followed by Dunnett’s test).
Pharmacological Effects of Mitragyna
speciosa Korth Extract
Med Princ Pract 2009;18:378–384
381
Effect of MSM in Carrageenan-Induced Paw Edema
Subplantar injection of carrageenan in control ani-
mals produced a local edema that increased progressive-
ly to a maximum intensity 3 h after the injection and then
gradually declined with time ( table 4 ). On the other hand,
MSM at doses of 100 and 200 mg/kg caused significant
(p ! 0.05) inhibition of the development of paw edema
with an activity higher than that of ASA (100 mg/kg),
with maximal percent of inhibition during the first 3 h
after challenge. In addition, pretreatment with ASA only
exhibited a significant inhibitory action on paw edema at
1 and 3 h after carrageenan injection, decreasing edema
formation by 44 and 60%, respectively. Nevertheless, the
group treated with 200 mg/kg MSM showed the best ac-
tivity, reducing edema by 60 and 63%, respectively, 4 and
5 h after carrageenan injection, even when the inhibitory
effects of the other treatments progressively declined.
Effect of MSM on Cotton Pellet-Induced Granuloma
Investigation of the effect of MSM on the proliferative
phase of inflammation revealed that daily administra-
tion of MSM (200 mg/kg) significantly (p ! 0.05) inhib-
ited the growth of granuloma tissue, provoking an in-
hibitory effect (44.9%) greater than that of ASA (25.4%)
when compared to the control group. In comparison, dai-
ly treatments of MSM (50 and 100 mg/kg) showed only
weak to moderate inhibitory effect with 16.9 and 21.6%
inhibition, respectively ( table 5 ).
Discussion
In the present study, the antinociceptive and anti-in-
flammatory effects of the M. speciosa leaves were investi-
gated in various related models in vivo. It was demon-
Tab le 3. Effect of MSM on the hot plate test in mice
Dose,
mg/kg
Latency time, s
0 30 60 120 180 240
Control – 4.9280.24 5.3780.54 5.8280.81 5.4980.72 5.2680.71 4.9980.60
MSM 50 5.5780.13 6.3780.52 7.6680.31 7.7980.38*6.4580.43 4.8980.34
100 5.1280.23 6.4980.56 7.9180.62*7.5180.80*6.4180.53 5.1280.51
200 4.5980.17 6.6480.47 6.7080.5*8.4080.50*7.5780.44*6.6880.44*
ASA 100 5.1480.23 6.0080.39 6.0780.63 5.6480.56 6.3780.34 6.3580.59
Morphine 5 5.1780.22 8.0780.60*9.1980.64*9.6480.62*8.5980.46*6.8880.57*
Morphine+naloxone 5+5 4.8980.22 5.3980.36** 6.5580.38** 8.5780.72** 6.4780.52** 5.9280.40**
MSM+naloxone 200+5 4.9880.21 5.5080.42** 5.6180.26** 7.7180.62** 5.8880.41** 4.8880.28**
Values are mean 8 SEM (n = 10). * p < 0.05 compared to the control. ** p < 0.05 compared to the group receiving appropriate drug/
extract at the same dose without naloxone (Dunnett’s test).
Tab le 4. Effect of MSM on carrageenan-induced hind paw edema in rats
Dose,
mg/kg
Edema, ml
1 h 2 h 3 h 4 h 5 h
Control – 0.4880.05 0.4780.06 0.5680.05 0.4780.03 0.4880.04
ASA 100 0.2780.06 (44)*0.4380.07 (9) 0.2880.05 (50)*0.3680.05 (23) 0.3980.06 (19)
MSM 50 0.2480.05 (50)*0.4480.04 (6) 0.3980.05 (30) 0.3580.04 (26) 0.4980.05 (NI)
100 0.1580.04 (69)*0.2580.04 (47)*0.2780.05 (52)*0.3180.03 (34) 0.4980.07 (NI)
200 0.1680.04 (67)*0.1580.04 (68)*0.2180.06 (63)*0.1980.06 (60)*0.1880.07 (63)*
Values are mean 8 SEM, while those in parentheses represent percent inhibition of edema (n = 8). NI = No inhibition. * p < 0.05
compared to the control group.
Shaik Mossadeq et al.
Med Princ Pract 2009;18:378–384
382
strated that MSM (100 and 200 mg/kg, i.p.) significantly
inhibited the mice’s writhing response in the acetic acid-
induced abdominal constriction test. It has been postu-
lated that acetic acid, which was used to induce writhing,
acts indirectly by releasing endogenous mediators that
stimulate pain nerve endings. Increased levels of PGE
2
and PGF
2 ␣
as well as in lipoxygenase, liberation of sym-
pathetic nervous system mediators in the peritoneal f luid
and the release of cytokines, such as TNF- ␣ , interleukin-
1  and interleukin- ␦ , by resident peritoneal macrophages
and mast cells have been reported to be responsible for
pa in s en satio n c ause d b y i.p . ad minist ra ti on o f acetic ac id
[15 –17] . The results also showed that ASA, known to in-
hibit cyclo-oxygenase
[18] , causes significant inhibition.
On the basis of this result, it can be assumed that the
mode of action of this activity might involve a peripheral
mechanism probably mediated via inhibition of lipoxy-
genases and/or cyclo-oxygenase activity. However, the
drawback of this model is that other drugs can cause a
similar effect, such as adrenergic antagonist and muscle
relaxants, leading to possible false-positive results
[19] .
Due to this, the formalin and hot plate tests were selected
to continue this investigation, since they are more spe-
cific and it is possible to identify two distinct phases of
nociception.
Formalin-induced nociception is a well-described
model and can be consistently inhibited by typical anal-
gesic and anti-inflammatory drugs, including morphine
and ASA
[12] . In this model, MSM (200 mg/kg) and mor-
phine inhibited the first and the second phase, while ASA
inhibited only the second phase of the formalin test. Con-
sidering the inhibitory property of MSM on the first and
second phases of the formalin test, we might suggest that
the extract contains active principles acting both central-
ly and peripherally, which also implies that the extract
possesses both antinociceptive and anti-inflammatory
activit y. Fu rthermore, the central ana lgesic effect of MSM
is supported by the results observed in the hot plate test,
a specific test used to elucidate central antinociceptive
properties of pain-relieving agents such as opioid-derived
analgesic drugs
[20] . In the hot plate model, morphine
and MSM (200 mg/kg) caused a significant increase in
the response latency time to the thermal stimulus, thus
confirming the central activity of the extract. In addition,
the results also showed that pretreatment with a nonse-
lective opioid receptor antagonist, naloxone, reversed the
antinociceptive effect of MSM as well as morphine in the
hot plate test. These findings clearly suggest that the an-
tinociceptive effect of MSM is mediated by activation of
the opioid system, which is in agreement with the previ-
ous findings
[3, 5] .
Carrageenan-induced rat paw edema is one of the con-
ventional tests used to evaluate the acute phase of the
anti-inflammatory effect of drugs and natural products
[21] . Carrageenan-induced inflammation is biphasic in
nature. The first phase is attributed to the release of his-
tamine and serotonin; the second phase results mainly
from the potentiating effects of bradykinin on mediator
release and also of prostaglandins, producing edema af-
ter the mobilization of leukocytes
[22] .
With respect to the first phase, the release of hista-
mine and other mediators produced increased vascular
permeability surrounding the site of damaged tissue re-
sulting in edema at the site. Therefore, inhibition of in-
creased vascular permeability and subsequent exudation
will, to some extent, implicate the extent of inflamma-
tory reaction produced at the site of injury. In this mod-
el, the subplantar injection of carrageenan in control an-
imals produced local edema, which increased progres-
sively to reach maximal intensity 3 h after the injection,
after which the effect gradua lly declined with time. How-
ever, MSM (100 and 200 mg/kg) inhibited the develop-
ment of paw edema more than ASA, demonstrating
maximum inhibition during the first 3 h after challenge,
and continued to do so even when the inhibitory effects
of the other treatments progressively declined. This sug-
gests that the extract may suppress the early phase of
edema, possibly by inhibiting the synthesis, release or
actions of the various hyperalgesic mediators which are
known to mediate acute inflammation induced by phlo-
gistic agents and thus produce reduced sensitivit y to pain
receptors
[23] . However, the inhibitory activity produced
by the extract at a dose of 200 mg/kg for a period of 4 h
may be attributed to the action of arachidonic acid and
Tab le 5. Effect of MSM on cotton pellet-induced granuloma test
in rats
Treatment Dose,
mg/kg, i.p.
Granuloma
weight, mg
Inhibition,
%
Control – 90.580.010 –
ASA 100 67.580.003*25.4
MSM 50 75.280.005 16.9
100 71.080.004 21.6
200 49.880.003*44.9
Values are mean 8 SEM (n = 8). * p < 0.05 compared to the
control group.
Pharmacological Effects of Mitragyna
speciosa Korth Extract
Med Princ Pract 2009;18:378–384
383
its metabolites, which at this stage produces edema de-
pendent on neutrophil mobilization
[24] . To gain further
insight into the chronic anti-inflammatory effects in-
duced by the extract, the granulomatous tissue induc-
tion model was employed. This procedure induced an
inflammatory process which involves proliferation of
modified macrophages, fibroblasts as well as the multi-
plication of blood vessels producing a highly vascular-
ized and reddened mass known as granulation tissue. In
this model, daily administration of MSM (200 mg/kg)
inhibited the growth of granuloma tissue, provoking an
inhibitory effect greater than that of ASA when com-
pared to the control group. A putative mechanism asso-
ciated with this activity may be due to the inhibition of
the synthesis of many mediators involved in the forma-
tion of fibrovascular tissue, including chemokines, cyto-
kines and eicosanoids
[25–27] . It is also unclear whether
the enhancement of immune response at this stage, if
any, may play a role in the inhibition of macrophage
transformation into epithelioid cells following injury.
This may account for the anti-inflammatory activities
produced by MSM in both the acute and chronic models
of in f l am m at io n e mp lo ye d. Ev en th ou g h t h e e xa c t m ec h -
anism of action is unknown, the anti-inflammatory ac-
tivity of M. speciosa may result from a combination of
inhibition of pro-inflammatory mediator release and
vascular permeability in addition to enhanced immu-
nity, stimulation of tissue repair and healing processes.
Furthermore, phytochemical analysis of MSM has
demonstrated the presence of alkaloids, saponins, flavo-
noids, tannins and sterols. The anti-inflammatory and/
or antinociceptive actions of these compounds have been
reported by many researchers. Moreover, the suppression
of inducible nitric oxide synthase and cyclo-oxygenase-2
enzymes has been shown for alkaloids and flavonoids
[28, 29] . Saponins have also been reported to have anti-
inflammatory activities by inhibition of the enzymes
inducible nitric oxide synthase, cyclo-oxygenase-2 and
lipoxygenase
[30] . Therefore, it seems that the anti-in-
flammatory and antinociceptive effects of MSM could
also be attributed to the presence of alkaloids, saponins,
flavonoids, tannins and sterols in the leaves of M. spe-
ciosa.
Conclusion
This study showed that MSM possesses antinocicep-
tive and anti-inflammatory properties. However, further
investigation is advocated to elucidate the active prin-
ciple(s) and exact mechanism(s) of its action.
A c k n o w l e d g m e n t s
We thank the staff of MARDI for technical assistance during
the preparation of extract and the Faculty of Medicine and Health
Sciences, Universiti Putra Malaysia for providing the necessary
support for the st udy. This resea rch was supported by a Funda men-
tal Res earch Grant Scheme (FRGS/FASA1-2006/(Sains Perubata n)/
UPM/179) from the Ministry of Higher Education Malaysia.
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