Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats
Analgesic and anti-inflammatory activities of an aqueous extract produced from Fadogia agrestis (family Rubiaceae) stem bark were investigated using animal models.
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Інститут фізіології ім. О.О. Богомольця НАН України
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irk-123456789-683382014-09-22T03:01:48Z Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats Oyekunle, O.A. Okojie, A.K. Udoh, U.S. Analgesic and anti-inflammatory activities of an aqueous extract produced from Fadogia agrestis (family Rubiaceae) stem bark were investigated using animal models. Знеболювальна й протизапальна активність водного екстракту, виготовленого з кори Fadogia agrestis (сімейство Маренові), вивчалася на щурах з використанням різних моделей болю та запалення. 2010 Article Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats / O.A. Oyekunle, A.K. Okojie, U.S. Udoh // Нейрофизиология. — 2010. — Т. 42, № 2. — С. 147-152. — Бібліогр.: 21 назв. — англ. 0028-2561 http://dspace.nbuv.gov.ua/handle/123456789/68338 612.06:582.936/1+58.072:615.89 en Нейрофизиология Інститут фізіології ім. О.О. Богомольця НАН України |
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Analgesic and anti-inflammatory activities of an aqueous extract produced from Fadogia agrestis (family Rubiaceae) stem bark were investigated using animal models. |
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Article |
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Oyekunle, O.A. Okojie, A.K. Udoh, U.S. |
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Oyekunle, O.A. Okojie, A.K. Udoh, U.S. Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats Нейрофизиология |
| author_facet |
Oyekunle, O.A. Okojie, A.K. Udoh, U.S. |
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Oyekunle, O.A. |
| title |
Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats |
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Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats |
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Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats |
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Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats |
| title_full_unstemmed |
Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats |
| title_sort |
analgesic and anti-inflammatory effects of an extract of fadogia agrestis in rats |
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Інститут фізіології ім. О.О. Богомольця НАН України |
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Analgesic and anti-inflammatory effects of an extract of Fadogia agrestis in rats / O.A. Oyekunle, A.K. Okojie, U.S. Udoh // Нейрофизиология. — 2010. — Т. 42, № 2. — С. 147-152. — Бібліогр.: 21 назв. — англ. |
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Нейрофизиология |
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2025-07-05T18:09:55Z |
| last_indexed |
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1836831468812238848 |
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НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2 147
UDC 612.06:582.936/1+58.072:615.89
O. A. OYEKUNLE,1 A. K. OKOJIE,2 AND U. S. UDOH1
ANALGESIC AND ANTI-INFLAMMATORY EFFECTS
OF AN EXTRACT OF FADOGIA AGRESTIS IN RATS
Received 03.12.09
Analgesic and anti-inflammatory activities of an aqueous extract produced from Fadogia
agrestis (family Rubiaceae) stem bark were investigated using animal models. Significant
dose-dependent increases in the reaction time in the tail-flick test and inhibition of writhing in
the visceral pain test (i.p. injections of acetic acid) with P up to < 0.001, when compared with
the control, were observed. In an anti-inflammatory investigation, we also found significant
dose-dependent inhibitions in the carrageenan-induced paw edema and cotton-pellet
granuloma tests. The extract in the highest non-sedative dose tested (200 mg/kg) demonstrated
a potency comparable with that of a reference analgesic anti-inflammatory drug, acetyl
salicylate (Aspirin, 100 mg/kg). Phytochemical screening revealed the presence of alkaloids
and saponins in the extract. The relieving effects of Fadogia are probably mediated by the
influences of active components of the extract on both central and peripheral nociceptive/
antinociceptive neural mechanisms. Therefore, our investigation explains the rationale behind
the ethnomedicinal usage of the mentioned plant to relieve pain and inflammation, as claimed
by local users, and shows that further studies of the mechanisms underlying the effects of the
remedy tested are expedient.
Keywords: Fadogia agrestis (Schweinf. ex Hiern), analgesic and anti-inflammatory
effects, tail-flick test, writhing, edema, granuloma.
1 Faculty of Basic Medical Sciences, Ladoke Akintola University of
Technology, Ogbomoso, Nigeria.
2 University of Benin, Benin, Nigeria.
Correspondence should be addressed to O. K. Okojie
(e-mail: pintos4live@yahoo.com).
INTRODUCTION
The quest for natural remedies has been on an increase
in the 21st century due to availability and affordability
challenges associated with a number of orthodox
remedies and also because of insufficient efficacy
and the existence of significant side effects typical
of many “standard” drugs. Pain and inflammation are
common ailments to which remedies are being sought
on everyday basis. Inflammation, a major causative
agent of human morbidity and mortality, such as the
systemic inflammatory response syndrome (SIRS)
and multiple organ dysfunction syndrome (MODS)
[1], is prevalent in many localities in the developing
countries as a result of inadequate health care and a
low level of health education. In response to these
challenges, many people “turn to nature.” One of the
local remedies sought in many African localities is the
stem bark of Fadogia agrestis (family Rubiaceae), a
shrub widely distributed in the forest coast of West
Africa. This plant was reported to be effective for
wound healing and against diarrhea. Certain effects
of the plant with respect to the sexual sphere were
also claimed [2, 3] and proven in a scientific research.
Since no literature is currently available to substantiate
possible analgesic and anti-inflammatory properties
of preparations obtained from the above plant, our
study was aimed at experimental testing the respective
properties of this plant as claimed by local users.
METHODS
Plant materials. The plant materials were collected
in Gambari, a suburb of Ogbomoso city in South
Western Nigeria, in February, 2009. The plant was
identified as Fadogia agrestis (Schveinf. ex Hiern)
and authenticated at the Forestry Research Institute
of Nigeria (FRIN), Ibadan. A voucher specimen was
deposited at the Institute.
Extract preparation. The stem bark of Fadogia
agrestis was dried at 40°C to a constant weight and
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2148
reduced to a coarse powder with the aid of a laboratory
grinder. An aqueous extract of the plant was obtained
by decoction in distilled water for 48 h at room
temperature. The obtained extract was filtered and
concentrated in a steam bath. Phytochemical screening
of the extract for identification of the constituents
using a standard protocol was performed [4].
Chemicals. Aspirin and carrageenan were purchased
from Sigma (Great Britain). All other chemicals were
of an analytical grade and procured locally.
Animals. Prepubertal male Wistar rats aged
about 4 weeks and weighing 70-100 g were used in
investigating the analgesic activity considering that a
pain-protection influence provided by testosterone in
adult rats was found in our earlier study [5]. Adult rats
weighing 200-250 g were used for examination of the
anti-inflammatory properties of the extract. All animals
were kept at 23 ± 2oC and a 12/12 h light/dark cycle
in the preclinical animal house of the Ladoke Akintola
University of Technology, Ogbomoso (Nigeria). The
animals were fed with standard rat pellet food and
provided with water ad libitum; they were acclimatized
for at least one week before the experimental sessions
in the laboratory. All the experimental procedures
were done following the experimental guidelines of
the Institutional Animal Ethics Committee (IAEC).
Each experimental procedure was applied to 5
animal groups with 5 rats in each group. Group 1
served as the control; groups 2-4 (treatment groups)
were subjected to the actions of the Fadogia extract.
All the doses mentioned below (50, 100, or 200 mg/kg)
are indicated for a dry residue of the extract. Group 5
(reference group) was treated with Aspirin (100 mg/kg).
Both Aspirin and the extract were administered
perorally using an oral cannula.
Tail immersion (tail-flick) test. The standard
procedure was used. Each animal for this procedure was
held in a suitable soft restrainer with the tail extending
out. The tail was up to 5 cm dipped into a beaker with
hot water maintained at 55 ± 0.1oC [6]. The time taken
for the rat to withdraw the tail (sec) was considered
the reaction time. Testings in groups 2-5 were carried
out 30, 60, and 120 min after administration of the
studied extract or Aspirin.
Acetic acid-induced writhing test. Thirty minutes
after administrations of the tested extract or Aspirin,
1% solution of acetic acid was i.p. injected into each
rat at a dose of 1 mg/100 g body mass [7]. The number
of writhing motor phenomena, such as contortions
and stretching, were counted within a 15-min-long
test interval. The normalized intensity of inhibition
of writhings was calculated, expressed as percentage,
and compared with the controls using the relation
(Nc – Nt)/Nc · 100%, where Nc and Nt are mean
numbers of writhings in the control (group 1) and test
groups 2-5, respectively.
Carrageenan-induced paw edema test. Acute
inflammation was produced in the hindlimb by injection
of 1% solution of carrageenan (0.1 ml/100 g body mass)
into the plantar surface of the hind paw [8] 30 min
after administrations of the extract or Aspirin. The paw
edema was measured at the intervals of 1, 2, 3, and
4 h using a plethysmometer. The normalized intensity
of suppression of paw edema among different animal
groups was compared using the formula analogous to
that mentioned above: (Vc – Vt)/Nc · 100%, where Vc
and Vt are mean increases in the paw volume in the
control and test groups, respectively.
Cotton pellet granuloma test. Rats were anesthetized
by i.p. ketamine injections, and 2-cm-long incision
was made on the rats’ groin region. An autoclaved
cotton pellet weighing 50 mg was implanted in this
region of each rat [9]. All the animals in each group
were dosed once for 7 days. On the 8th day, animals
were sacrificed by cervical dislocation, and the cotton
pellet along with the granuloma tissue was extracted
and dried in an oven at 55oC for 24 h. The resulting
cotton pellet weights were compared with the control,
and the normalized intensity of inhibition of the
development of granuloma by the tested remedies was
calculated.
The numerical data are represented as means ±
± s.e.m.; Student’s t-test was performed, and P < 0.05
values were considered as confirming a significant
intergroup difference.
RESULTS
Introduction of the extract of Fadogia agrestis bark
to experimental rats led to significant suppression of
the tail-flick reflex induced by noxious stimulation
of thermonociceptors in the tail skin. The effect
demonstrated a clear dose dependence. When 50 or 100
mg of the extract dry residue per 1 kg of the body mass
were introduced, the delay of the tail flick movement
showed twofold to threefold increases or more, as
compared with the mean delay in the control group 1.
When the highest tested dose (200 mg/kg, group 4) was
used, the tail flick delay reached 490-577% of that in the
control group. Thus, the analgesic effect of the extract
introduced in a dose of 200 mg/kg was weaker than
O. A. OYEKUNLE, A. K. OKOJIE, and U. S. UDOH
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2 149
that of 100 mg/kg Aspirin (the latter latency increase in
the test used was eight- to ninefold or more) but quite
comparable with the effect of the above-mentioned
well-known and extensively used (“classic”) anti-
nociceptive and anti-inflammatory drug. The effects of
the extract were rather stable within the observation
period (2 h) and even became somewhat more intense
within this time interval (Fig. 1A-C).
In the test where visceral pain was induced (i.p.
injection of acetic acid solution), the Fadogia extract
also demonstrated significant analgesic effects. Thirty
minutes after extract administration, introductions of
all the three doses used resulted in decreases in the
number of writhing motor effects observed within a
15-min-long observation interval. The antinociceptive
effect was relatively mild (a 12.6% decrease) at the
lowest dose (50 mg/kg) used; but in the case where
200 mg/kg of the extract dry residue were introduced,
the number of writhings dropped more than two times.
For comparison, 100 mg/kg Aspirin caused an about
threefold decrease in the number of writhings (Fig. 2).
In control rats, injection of carrageenan (0.2 ml of 1%
solution per 100 g of the body mass) into the hindpaw
plantar surface resulted in the development of edema in
the injured limb. One hour after carrageenan injection,
the edema volume was, on average, 1.81 ± 0.01 ml,
and the volume increased to 1.94 ± 0.01 ml (a 7.2%
rise, P < 0.05) on the 4th h. The Fadogia extract in the
50 mg/kg dose decreased the edema volume within this
0
2
4
6
8
10
12
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16
0
2
4
6
8
10
12
14
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0
2
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1 2 3 4 5
Fig. 1. Analgesic activity of the extract of Fadogia agrestis in
the tail-flick test. Diagrams of the mean delays (sec) of tail-flick
movements (±s.e.m.) observed in different groups of animals
(5 rats each) 30, 60, and 120 min (shown at the right, A-C) after
introductions of 50, 100, and 200 mg/kg of the extract (groups 2-4,
respectively) and of 100 mg/kg Aspirin (group 5). The data for the
control group 1 are also shown. Two and three asterisks show cases
of significant differences with P < 0.01 and P < 0.001 from the
values in the control group 1.
Р и с. 1. Знеболювальна активність екстракту Fadogia agrestis у
тесті відсмикування хвоста.
А
sec
B
C
**
**
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30
60
***
***
****
120 min
***
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****
0
5
10
15
20
25
30
35
40
1 2 3 4 5
Fig. 2. Analgesic activity of the Fadogia extract in the acetic acid-
induced writhing test. Diagrams of the mean numbers of writhings
within a 15-min-long observation period 30 min after introduction
of the remedies tested. One asterisk shows significant difference
with P < 0.05 from the values in group 1. Other designations are
similar to those in Fig. 1.
Р и с. 2. Знеболювальна активність екстракту Fadogia agrestis у
тесті корчів, викликаних уведенням оцтової кислоти.
***
***
***
*
ANALGESIC AND ANTI-INFLAMMATORY EFFECTS
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2150
period by 5.5 to 16.0%, while the respective decrease
at the 200 mg/kg dose varied from 42.0 to 62.4%. The
latter effect was again quite comparable with a positive
effect of Aspirin in the dose used, namely from 61.3 to
71.1% (Fig. 3A-D).
These results agreed well with the results of the
cotton pellet granuloma test. At the extract dry residue
doses 50, 100, and 200 mg/kg, the normalized masses
of the pellet, as compared with the corresponding
index in the control group 1, were smaller by 16.5,
46.3, and 78.9%, respectively. Administration of
Aspirin provided a 87.1% decrease in the pellet mass;
so, the anti-inflammatory efficacy of the extract in the
highest dose used was again quite comparable with
that of Aspirin in a rather high dosage.
DISCUSSION
The results of our study showed that the aqueous extract
of Fadogia agrestis (Schweinf. ex Hiern) stem bark
induces considerable dose-dependent analgesic effects
against the writhing syndrome observed in the acetic
acid test. These abdominal writhes, which result from
the action of severe visceral pain [10], are probably
suppressed mostly by a peripheral analgesic effect
of the remedies tested [11–13]. In peripheral tissues,
the development of pain is mostly a consequence
0
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0.4
0.6
0.8
1.0
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1.4
1.6
1.8
2.0
0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
0
0.5
1.0
1.5
2.0
2.5
0
0.5
1.0
1.5
2.0
2.5
1 2 3 4 5
Fig. 3. Anti-inflammatory activity of the Fadogia extract in the
carrageenan-induced paw edema test. Diagrams of mean increases
in the paw volume (ml) resulting from edema 1, 2, 3, and 4 h after
carrageenan injection (A-D, respectively). Designations are similar
to those in Figs. 1 and 2.
Р и с. 3. Протизапальна активність екстракту Fadogia agrestis у
тесті набряку лапи, індукованого введенням карагеніну.
Аml
*
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***
B
*
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*
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******
**
*
C
D
0
20
40
60
80
100
120
1 2 3 4 5
*
**
**
***
Fig. 4. Anti-inflammatory activity of the Fadogia extract in the
cotton pellet granuloma test. Diagrams of normalized mean weights
of the pellet (%; weight in the control group 1 is taken as 100%).
Other designations are similar to those in Fig. 1-3.
Р и с. 4. Протизапальна активність екстракту Fadogia agrestis у
тесті гранульоми, індукованої імплантацією ватного тампона.
%
O. A. OYEKUNLE, A. K. OKOJIE, and U. S. UDOH
***
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2 151
of sensitization of the chemosensitive nociceptors
by prostaglandins [14]. The result obtained in this
model, therefore, suggests that the pain-suppressing
effect of the extract may be due to inhibition of
prostaglandin synthesis. However, our suggestion on
an analgesic effect of the extract was not based on
this model alone, because several compounds, such as
tricyclic antidepressants [15] and histamine [16], also
exhibit suppression of the writhing syndrome. A more
specific model (tail immersion test) based on noxious
stimulation of thermonociceptors was employed
to investigate the analgesic potential of the extract
against this type of pain. The result showed clear dose-
dependent increases in the reaction time in the above
test. This model provides an evidence that the extract
exerts not only peripheral effects on nociceptors but
probably possesses some central action on the spinal
and cerebral antinociception neuronal systems [17].
We also investigated the anti-inflammatory
potential of the extract. Inflammatory events
involve microvascular changes with increased
vascular permeability, flow of exudation (including
plasmatic proteins), and increase in the amounts
of endogenous mediators [18]. Non-steroidal anti-
inflammatory drugs (NSAIDs) are common means
against superficial nociception and inflammation.
NSAIDs alleviate hyperalgesic symptoms associated
with inflammation by inhibiting the cyclooxygenase
activity and by resultant inhibition of prostaglandin
synthesis from arachidonic acid [19]. Our results
demonstrated intense dose-dependent inhibitions of
paw edema (in the carrageenan-induced paw edema
model) and the development of granuloma (in cotton
pellet granuloma model). The maximum nonsedative
dose offered the highest level of protection in both
models of inflammation, probably mostly by inhibiting
prostaglandin synthesis.
As was mentioned above, the Fadogia extract
exerted analgesic and anti-inflammatory effects
quite comparable in their intensity with the effects
of the “standard” NSAID Aspirin, one of the most
extensively used remedies. It should be taken into
account that we used in our tests a rather high dose of
this drug (which is much higher than the doses usually
introduced in clinics) to provide the most demonstrative
antinociceptive and anti-inflammatory effect in the
reference animal group. Naturally, the Fadogia extract
can demonstrate even stronger analgesic effects, as
compared with those of smaller Aspirin doses.
Phytochemical screening results confirmed that
significant amounts of alkaloids and saponins, the
constituents which have been reported in other
members of the botanical family Rubiaceae and
identified as potent analgesics, are present in the
Fadogia extract; much lesser amounts of flavonoids
and antraquinone were also found [20, 21]. These
constituents could be responsible for analgesic and
anti-inflammatory potentials of the studied extract. We
hereby suggest that further studies on characterization
and identification of the molecular structure of different
constituents present in the extract and the possibilities
for its applicability in medicinal chemistry and for the
development of novel remedies are rather expedient.
Of course, this also presupposes the necessity of
technological perfection of preparation of clinically
usable drugs from plant raw materials and detailed
clinical testing of such remedies.
Acknowledgments. We express our gratitude to the head
of the Department of Physiology and Management of the
Preclinical Animal House at the Ladoke Akintola University of
Technology, Ogbomoso (Nigeria).
О. А. Ойєкунле1, А. К. Окойє2, Ю. С. Удо1
ЗНЕБОЛЮВАЛЬНІ Й ПРОТИЗАПАЛЬНІ ЕФЕКТИ
ЕКСТРАКТУ FADOGIA AGRESTIS У ЩУРІВ
1 Технологічний університет Ладоке Акінтола, Огбомозо
(Нігерія).
2 Бенінський університет (Нігерія).
Р е з ю м е
Знеболювальна й протизапальна активність водного
екстракту, виготовленого з кори Fadogia agrestis (сімейство
Маренові), вивчалася на щурах з використанням різних
моделей болю та запалення. Екстракт забезпечував
дозозалежне збільшення часу реакції в тесті відсмикування
хвоста та посилення гальмування корчів у тесті вісцерального
болю (індукованого внутрішньоочеревинними ін’єкціями
оцтової кислоти) з Р аж до <0.001 порівняно з контролем.
Вивчаючи протизапальні ефекти екстракту Fadogia, ми
також виявили значне дозозалежне пригнічення запалення
в тестах набряку лапи, індукованого введенням карагеніну,
та розвитку гранульоми, індукованого імплантацією
ватного тампона. Цей екстракт, застосований у найвищій
неседативній дозі (200 мг/кг), демонстрував ефективність,
цілком порівняну з такою еталонного знеболюючого і
протизапального агента – ацетилсаліцилата (аспірину,
100 мг/кг). Фітохімічний скринінг дозволив нам виявити в
екстракті присутність алкалоїдів, сапонінів та флавоноїдів.
Знеболювальні ефекти Fadogia опосередковуються,
вірогідно, впливами активних компонентів екстракту як
на центральні, так і на периферичні нервові ноцицептивні/
антиноцицептивні механізми. Отже, результати наших
досліджень логічно обгрунтовують ефекти використання
ANALGESIC AND ANTI-INFLAMMATORY EFFECTS
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 2152
згадуваної рослини в етнічній медицині з метою ослаблення
болю й пригнічення запалення, а також свідчать про
доцільність подальшого вивчення механізмів, що лежать в
основі дії тестованого лікувального засобу.
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O. A. OYEKUNLE, A. K. OKOJIE, and U. S. UDOH
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