Anti-inflammatory Activity of Cucumis sativus L

Abstract

Aims: To evaluate the anti-inflammatory activity and acute toxicity of Cucumis sativus L. Study Design: Animal model assays of anti-inflammatory. Place and Duration of Study: Methodology: To evaluate anti-inflammatory activity, test substances that included whole Cucumis sativus L. homogenate were administered to four groups of Wistar rats. A control group received normal saline; a reference group received a standard anti-inflammatory drug, Diclofenac while 2 test groups received whole Cucumis sativus L. fruit homogenate, respectively. Inflammation of the right hind paw of rats was induced by subplantar injection of 0.1 ml of 2% agar-agar suspension and increases in paw volumes, which relate to anti-inflammation, were measured using the volume displacement method. To evaluate the acute toxicity of Cucumis sativus L. fruit homogenate, 20 albino mice grouped into five groups of four mice each with animals were used. Animals in different groups were orally administered with different amount of the whole fruit homogenate. The animals were monitored for dullness, nervousness, uncoordinated movement, and death within 24 hours after administration. Original Research Article Agatemor et al.; BJPR, 8(2): 1-8, 2015; Article no.BJPR.19700 2 Results: Paw volume progressive decreased within 5.5 hours in test groups after administration of Cucumis sativus L. The administered Cucumis sativus L did not induce adverse effects on the mice within the concentration range of 0.5 mL/kg body weight to 5 mL/kg body weight test animals. Conclusion: The whole fruit homogenate of Cucumis sativus L. had anti-inflammatory activity and no dose-dependent side effects.

Full text

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*Corresponding author: Email: MGATEMOR@GMAIL.COM, CAGATEMOR@UPEI.CA;
British Journal of Pharmaceutical Research
8(2): 1-8, 2015, Article no.BJPR.19700
ISSN: 2231-2919
SCIENCEDOMAIN international
www.sciencedomain.org
Anti-inflammatory Activity of Cucumis sativus L.
Uzuazokaro Mark-Maria Agatemor
1*
, Okwesili Fred Chiletugo Nwodo
1
and Chioma Assumpta Anosike
1
1
Department of Biochemistry, University of Nigeria, Nsukka, Enugu State 410001, Nigeria.
Authors’ contributions
This work was carried out in collaboration between all authors. Author UMMA designed the study,
wrote the protocol, and wrote the first draft of the manuscript. Authors UMMA and OFCN managed
the literature searches, analyses of the study performed the spectroscopy analysis and authors
UMMA and CAA managed the experimental process and author UMMA identified the species of the
plant. All authors read and approved the final manuscript.
Article Information
DOI: 10.9734/BJPR/2015/19700
Editor(s):
(1)
Vasudevan Mani, Universiti Teknologi MARA (UiTM), Selangor, Malaysia.
Reviewers:
(1)
Anonymous, Khon Kaen University, Thailand.
(2)
Anonymous, Universiti Putra Malaysia, Malaysia.
(3)
Anonymous, University of Haripur, Pakistan.
Complete Peer review History:
http://sciencedomain.org/review-history/10635
Received 23
rd
June 2015
Accepted 4
th
August 2015
Published 23
rd
August 2015
ABSTRACT
Aims:
To evaluate the anti-inflammatory activity and acute toxicity of Cucumis sativus L.
Study Design: Animal model assays of anti-inflammatory.
Place and Duration of Study: Department of Biochemistry, University of Nigeria, Nsukka, Enugu
State, 410001, Nigeria between April 2014 and November 2014.
Methodology: To evaluate anti-inflammatory activity, test substances that included whole
Cucumis sativus L. homogenate were administered to four groups of Wistar rats. A control group
received normal saline; a reference group received a standard anti-inflammatory drug, Diclofenac
while 2 test groups received whole Cucumis sativus L. fruit homogenate, respectively.
Inflammation of the right hind paw of rats was induced by subplantar injection of 0.1 ml of 2% agar-
agar suspension and increases in paw volumes, which relate to anti-inflammation, were measured
using the volume displacement method. To evaluate the acute toxicity of Cucumis sativus L. fruit
homogenate, 20 albino mice grouped into five groups of four mice each with animals were used.
Animals in different groups were orally administered with different amount of the whole fruit
homogenate. The animals were monitored for dullness, nervousness, uncoordinated movement,
and death within 24 hours after administration.
Original Research Article

Agatemor et al.; BJPR, 8(2): 1-8, 2015; Article no.BJPR.19700
2
Results:
Paw volume progressive decreased within 5.5 hours in test groups after administration of
Cucumis sativus L. The administered Cucumis sativus L did not induce adverse effects on the mice
within the concentration range of 0.5 mL/kg body weight to 5 mL/kg body weight test animals.
Conclusion: The whole fruit homogenate of Cucumis sativus L. had anti-inflammatory activity and
no dose-dependent side effects.
Keywords: Cucumis sativus L.; inflammation; anti-inflammation; antioxidant; acute toxicity.
1. INTRODUCTION
Inflammation is a public health concern as it is a
central attribute of biological response towards
infections or injuries. When chronic or
deregulated, this beneficial response may retard
healing, and ultimately trigger diseased
conditions in many organisms including humans
[1,2]. To mitigate the adverse effects of
inflammation in humans, effort is focused on the
use of nonsteroidal anti-inflammatory drugs, [2-6]
and disease-modifying antirheumatic drugs
[2,7-9]. Although these drugs are efficacious in
treating inflammation-triggered disorders, dose-
dependent side effects are evidenced [2]. In
addition, none of these drugs are primary
preventive measures [2]. For instance, increased
risk of upper gastrointestinal disorder is
associated with the use of nonsteroidal anti-
inflammatory drugs [6,10,11]. Consequently,
inflammation-management platforms with
attenuated side effects are critically needed.
An important component of these platforms are
dietary mixes that incorporate variety of fish oil,
tea, cocoa and chocolate [2] as well as fruits,
vegetables, whole grains, and nuts [12-15].
Intake of a variety of fruits, and vegetables
lowers risk of inflammation, and relates inversely
with inflammation biomarkers, such as C-reactive
protein, interleukin-6, tumour necrosis factor-α
[16,17]. The inverse relation of fruits and
vegetable with these biomarkers is due to the
presence of bioactive phytochemicals, such as
polyphenols, omega-3 fatty acids, and dietary
fibre in fruits and vegetables.
Cucumber (Cucumis sativus, L.) is an edible fruit
that belongs to the Cucurbitaceae family [18],
and is rich in some of the aforementioned
bioactive phytochemicals [19,20]. As an
example, bioactive phenolic compounds are
present in methanol/water extracts of fresh
Cucumis sativus L. [21]. Further, methanol
extract of the leaves of Cucumis sativus L.
contains C-glycosyl flavonoids, phytochemicals
that are linked in the defense mechanism of the
plant [22]. Given the plethora of bioactive
phytochemicals in Cucumis sativus L., its use in
folk medicine in the management of several
health disorders that include diabetes mellitus,
hypertension and inflammation is understandable
[21]. Indeed, extracts of Cucumis sativus L.
exhibit anticancer [20], antioxidant [23-25],
antimicrobial [24,26], antidiabetic [27], analgesic
[28] and antiulcer [25] properties. In Africa,
Cucumis sativus L. is applied in the treatment of
tropical sprue, a malabsorption disease
characterized by flattering of the villi and
inflammation of the linings of the small intestine
[29]. Indeed, Cucumis sativus L. fruits is
recommended as a dietary treatment for tropical
sprue [30]. Despite the recommendation on the
use of Cucumis sativus L. in the management of
tropical sprue, an inflammatory-related disease
as well as the anti-inflammatory activity of its
seeds [31], to the best of our knowledge, the
anti-inflammatory properties of the whole fruit is
yet to be empirically established [19]. Here, we
show the anti-inflammatory activity of whole
Cucumis sativus L. fruit homogenate using
animal models. We also examined the
antioxidant activity as well as the acute toxicity of
the whole fruit homogenate. Our results highlight
the potential pharmaceutical function of the
whole fruit homogenate in the treatment of
inflammation.
2. MATERIALS AND METHODS
2.1 Chemicals, Plant Materials and
Animal Models
All the chemicals and reagents were of analytical
grade, and were used as obtained from the
suppliers. Fresh whole Cucumis sativus L. fruits
were purchased from Nsukka main market,
Nsukka, Nigeria and were identified at the
Bioresources Development and Conservation
Programme Research Center, Nsukka, Nigeria.
The fruits were homogenized using high-speed
blender and administered without dilution.
Twenty albino mice of Swiss strain (22–28 g)
were used for index of acute toxicity study while
sixteen Wistar rats (120–200 g) were used for
anti-inflammatory.

Agatemor et al.; BJPR, 8(2): 1-8, 2015; Article no.BJPR.19700
3
2.2 Anti-inflammation Assay
The rat paws oedema method of Winter et al.
[32] as modified previously [33] was used to
evaluate the anti-inflammatory activity of the
whole Cucumis sativus L. fruit homogenate. Prior
to the studies, the rats were grouped into four
groups (1-4) of four rats each, were acclimatized
for seven days, fasted and deprived of water for
18 hours. Anti-inflammatory test substance was
orally administered 1 h before inducing
inflammation. The control group 1 received
normal saline (5 mL/kg body weight (b.w.)), the
reference group 2 received a standard anti-
inflammatory drug, Diclofenac®, (150 mg/kg
b.w.) while test groups 3 and 4 received 2 mL/kg
b.w. and 4 mL/kg b.w. of whole Cucumis sativus
L. fruit homogenate, respectively. Inflammation of
the right hind paw was induced by subplantar
injection of 0.1 ml of 2% agar-agar suspension.
The changes in paw volumes were measured
using the volume displacement method [33]
immediately before agar-agar injection and 1.5,
3.0 and 5.5 hours after injection. The percentage
inhibition of oedema was calculated as described
[34].
2.3 Determination of Phenolic, Flavonoid
and Anthocyanin Contents
The phenolic, flavonoids and anthocyanin
content of the homogenate were determined
using reported protocols [35]. As an example,
total phenols was determined as follows: 2 g of
the homogenate was macerated in 20 ml of 80%
ethanol for 5 minutes, centrifuged for 10 minutes
and 1 mL of the supernatant was transferred into
a test tube. To this was added 4 mL of distilled
water and 0.5 mL of Folin-Ciocalteu reagent,
followed by 2 mL of 20% Na
2
CO
3
. The mixture
was allowed to stand for 90 minutes, and the
absorbance was taken at 760 nm using SP
500 Spectrophotometer, Pye Unicam. The
measurements, which were taken in triplicates,
were compared against a standard curve of
prepared gallic acid solutions and expressed as
milligram of gallic acid equivalent (GAE) per
gram of homogenate. To ascertain the flavonoid
content, 5 mL of the supernatant was transferred
to a test tube. To this was added 0.3 mL of 5% of
sodium nitrite solution and the mixture was
allowed to stand for 5 minutes. Thereafter, 0.3
mL of 10% ferric chloride was added and the
mixture was allowed to stand for another 6
minutes. Then 4 mL of 4% sodium hydroxide was
added and the absorbance was measured
immediately and after 15 minutes of incubation at
room temperature. For the anthocyanin content,
2 g of the homogenate was macerated in 20 mL
of sodium citrate pH 3.4 buffer, centrifuged for 5
minutes and 2 mL of supernatant was transferred
into two different test tubes. Then, 4 mL of citrate
buffer was added to one test tube and a 1:1
HCl:H
2
O mixture was added to the other test
tube. The absorbance of the mixtures was taken
at 500 nm after 1 hour using water as blank. The
flavonoid and anthocyanin contents were
determined in triplicates and expressed as
milligram of catechin equivalents and cyanidin 3-
glucoside equivalents per gram of homogenate,
respectively [34].
2.4 DPPH Radical Scavenging Assay
The radical scavenging activity of whole
Cucumis sativus L. fruit homogenate and a
standard, vitamin E, was determined
spectrophotometrically using the stable radical
scavenger, 2, 2-diphenyl-2-picrylhydrazyl hydrate
(DPPH) as reported [36] but with slight
modifications. A quantity, 2 g, of fruit
homogenate was macerated with 20 mL of
ethanol, centrifuged and 0.1 mL of the
supernatant measured into a test tube. This was
followed by the addition of 0.9 mL with absolute
ethanol and 0.5 mL of 0.3 mM DPPH. The
mixture was kept in the dark for 30 min at room
temperature. Thereafter, decrease in absorption
was measured at 518 nm using SP 500
Spectrophotometer, Pye Unicam. The absorption
of a blank that contained the same amount of
absolute ethanol and DPPH was also measured
and the percentage inhibition was calculated as
reported previously [32]. All measurements were
carried out in triplicates.
2.5 Index Acute Toxicity Studies
The method of Lorke [37] was used to ascertain
the acute toxicity of Cucumis sativus L
homogenate. Twenty albino mice were used in
this study. Prior to the study, the animals were
acclimatized for seven days, starved of food for
18 hours but allowed access to water. The
animals were grouped into five groups (5-9) of
four mice each with animals. Animals in groups
5,6,7,8 and 9 were orally administered with 0.5,
1.01.5,3.0,5.0 mL/kg body weight of the whole
fruit homogenate, respectively. The animals were
frequently observed after administration of the
homogenate for adverse effects that
included dullness, nervousness, uncoordinated
movement, and death within 24 hours.

Agatemor et al.; BJPR, 8(2): 1-8, 2015; Article no.BJPR.19700
4
2.6 Statistical Analysis
All analyses were run in triplicate and results are
expressed as mean±SEM. Tests of statistical
significance were carried out using two-way
analysis of variance (ANOVA). The Statistical
Product and Service Solutions (SPSS) using IBM
version 20 was used and P = .05 were
considered significant.
3. RESULTS AND DISCUSSION
A growing number of scientific investigations
support food-based strategy in the management
and treatment of diseases including inflammation
[2] and this approach is popular in folk medicine.
For instance, Africa folk medicine, Cucumis
sativus L. is used to attenuate and mitigate
tropical sprue, a disease characterized by the
flattering of the villi and inflammation of the
linings of the small intestine. Again, in Puerto
Rico, the consumption of Cucumis sativus L. is a
recommended remedy for the treatment of
tropical sprue [30]. Despite the
ethnopharmaceutical applications of this fruit,
specifically in the treatment of tropical sprue,
scientific research is yet to verify this potential.
As tropical sprue is accompanied by the
inflammation of the lining of the small intestine, it
would, therefore, be interesting and worthwhile to
investigate the role of Cucumis sativus L. in the
mitigation of chronic inflammation. In this report,
we focus on the role of whole Cucumis sativus L.
fruit homogenate in the mitigation of inflammation
using a modified rat paw oedema method.
Similar to carrageenan-induced inflammation,
agar-induced inflammation in rat paw is biphasic.
The early phase, which lasts up to 2 hours after
administration of the agar-agar irritant, is
prompted by the release histamine, 5-hydroxyl
tryptamine, kinin and serotonin [38,39]. The
later phase commences after 2 hours of
irritant administration and last till 5 hours
and is triggered by bradykinin, protease,
prostaglandins, and lysosome [38,39]. Thus, in
this study, the paw volume was monitored within
5.5 hours. A progressive decrease in paw
volume within this time frame was observed in
test groups 3 and 4 that received whole Cucumis
sativus L. fruit homogenates (Fig. 1). In addition
to the decrease in paw volume, these groups
also exhibited lower paw volume as compared to
animals in control group 1 (Fig. 1). Also
increasing the amount of Cucumis sativus L.
homogenate from 2 mL/kg body weight (b.w.) to
4 mL/kg b.w. reduced paw volume in the test
groups (Fig. 1). This suggested that Cucumis
sativus L is an anti-inflammatory food-based
pharmaceutical. The anti-inflammatory activity is
due to the presence of bioactive phytochemicals
that inhibits the release or mitigates the action of
pro-inflammation mediators [2,15,16].
To gain an insight into the levels of
phytochemicals in the assayed Cucumis sativus
L. we determined the amount of total
polyphenols, flavonoids and anthocyanin in the
whole fruit homogenate (Table 1). Appreciable
amounts of anthocyanin (1.21±0.39 mg of
cyanidin 3-glucoside equivalent/g of
homogenate), flavonoids (2.14±0.56 mg of
catechin equivalents/g of homogenate) and
polyphenols (8.51±0.50 mg of GAE/g of
homogenate) were found in the fruit
homogenate. The result of phytochemical
screening contrasted those of Jony and Roksana
[39] who reported the absence of flavonoids in
the ethanol extract of Cucumis sativus. It could
be that flavonoids were not detected as a result
of the extraction method used, as Kumar et al.,
[28] reported the presence of flavonoids in the
aqueous extract, thus correlating the findings of
this investigation. Polyphenols exhibit anti-
inflammatory activities via inhibiting the action of
pro-inflammatory enzymes, modulating the
production of pro-inflammatory molecules,
inhibiting pro-inflammatory cell adhesion
molecules, and/or scavenging reactive oxygen
species (ROS) [2]. As radical species, ROS
enhances inflammation via the activation of
inflammatory genes that include nuclear factor
κB, and polyphenols regulates these genes by
scavenging ROS or increasing the antioxidant
activities. The antioxidant activities of the
homogenate were also determined using the
DPPH radical scavenging assay. The essence of
DPPH method is the reaction of antioxidants with
1, 1-diphenyl-2-picryl hydrazyl (DPPH), resulting
in discoloration of the latter. The degree of
discoloration at 518 nm is a measure of the
antioxidant activity [40]. Good antioxidant
activities as evidenced from the decrease in the
mean absorbance value and increase in the
percentage inhibition of DPPH (Table 2) was
found in the assayed Cucumis sativus L. This
observation on the DPPH radical scavenging
activity of the homogenate of Cucumis sativus L
fruit was in agreement with that of Agarwal et al.
[41].

Table 1. Quantitative phytochemical
constituents of the homogenate of
Cucumis sativus
L. fruit
Phytochemical
Composition (mg/g)
Polyphenol 8.51±
0.50
Flavonoid 2.14±
0.56
Anthocyanin 1.21±
0.39
a
Polyphenol, flavonoid, and anthocyanin contents are
expressed as milligram of gallic acid equivalent,
milligram of catechin equivalents, and cyanidin
3-
glucoside equivalents per gram of homogenate,
respectively
To compare the anti-
inflammatory activity of our
homogenate with commercially available anti
inflammatory drugs, Diclofenac® a commercially
available anti-
inflammatory drug was
administered to animals in reference group 2.
The administration
of 4 mL/kg b.w. of the whole
Cucumis sativus
L. whole fruit homogenate to
Fig.
1. Change in rat paw volume in the different groups. Control group 1, administrated with
5 mL/kg b.w. normal saline; reference group 2, administrated with 150 mg/kg b.w. Diclofenac
test group 3, administered 2 mL/kg b.w. whole
group 4, administered 4 mL/kg b.w. whole
Agatemor et al.; BJPR, 8(2): 1-8, 2015
; Article no.
5
Table 1. Quantitative phytochemical
constituents of the homogenate of
L. fruit
Composition (mg/g)
a
0.50
0.56
0.39
Polyphenol, flavonoid, and anthocyanin contents are
expressed as milligram of gallic acid equivalent,
milligram of catechin equivalents, and cyanidin
glucoside equivalents per gram of homogenate,
inflammatory activity of our
homogenate with commercially available anti
-
inflammatory drugs, Diclofenac® a commercially
inflammatory drug was
administered to animals in reference group 2.
of 4 mL/kg b.w. of the whole
L. whole fruit homogenate to
test group 4 animal models suppressed oedema
to an extent similar to that of Diclofenac® after
5.5 hours (Fig.
1). This result demonstrates the
potential of Cucumis sativus
L. as a c
platform to commercially available synthetic anti
inflammatory drugs for treating inflammation.
Unlike these synthetic drugs, the whole fruit
homogenate of
Cucumis sativus
have dose-
dependent side effects. To test this
hypothesis, acu
te toxicity studies of the whole
fruit homogenate were conducted using a
modified Lorke method [36]. This method, which
applies to agricultural produce as well, provides
acceptable information on the lethal dose (LD
using small number of experimental an
No mortality or uncoordinated movements was
observed with gradual increase in the
administered dose of
Cucumis sativus
mL/kg b.w. to 5 mL/kg b.w. (Table 2). This
findings support our hypothesis, demonstrating
the absence of dose-depe
ndent side effects.
1. Change in rat paw volume in the different groups. Control group 1, administrated with
5 mL/kg b.w. normal saline; reference group 2, administrated with 150 mg/kg b.w. Diclofenac
test group 3, administered 2 mL/kg b.w. whole
Cucumis sativus
L. fruit homogenates; and test
group 4, administered 4 mL/kg b.w. whole
Cucumis sativus
L. fruit homogenates
; Article no.
BJPR.19700
test group 4 animal models suppressed oedema
to an extent similar to that of Diclofenac® after
1). This result demonstrates the
L. as a c
omparable
platform to commercially available synthetic anti
-
inflammatory drugs for treating inflammation.
Unlike these synthetic drugs, the whole fruit
Cucumis sativus
L. does not
dependent side effects. To test this
te toxicity studies of the whole
fruit homogenate were conducted using a
modified Lorke method [36]. This method, which
applies to agricultural produce as well, provides
acceptable information on the lethal dose (LD
50
)
using small number of experimental an
imals [37].
No mortality or uncoordinated movements was
observed with gradual increase in the
Cucumis sativus
L from 0.5
mL/kg b.w. to 5 mL/kg b.w. (Table 2). This
findings support our hypothesis, demonstrating
ndent side effects.
1. Change in rat paw volume in the different groups. Control group 1, administrated with
5 mL/kg b.w. normal saline; reference group 2, administrated with 150 mg/kg b.w. Diclofenac
®;
L. fruit homogenates; and test
L. fruit homogenates

Agatemor et al.; BJPR, 8(2): 1-8, 2015; Article no.BJPR.19700
6
Table 2. DPPH radical scavenging activity of
the whole Cucumis sativus L. homogenate
fruits and vitamin E.
Test sample
(mL)
Δ Mean
absorbance
value
(mean±SEM
a
)
% Inhibition
b
0.1
0.421±0.001
50.8
0.2 0.411±0.003
52.0
0.3 0.380±0.005
55.6
0.4 0.349±0.004
59.6
0.5 0.340±0.002 60.3
Vitamin E
c
0.321±0.001
62.5
Control 0.857±0.003 -
a
SEM was significant at P = .05 compared to control.
b
Percentage inhibition of radical formation was
calculated relative to control.
c
The concentration and
volume of vitamin E used were 0.1 mg/mL and 0.5 mL,
respectively
Table 3. Result of acute toxicity test
Group
Dosage
(mL/kg b.w)
Number of
dead animals/total
number of animals
5 0.5 0/4
6 1.0 0/4
7 1.5 0/4
8 3.0 0/4
9 5.0 0/4
4. CONCLUSION
Cucumis sativus L. is used in folk medicine as a
treatment of tropical sprue, an inflammatory-
related disease. We investigated the anti-
inflammatory activity of Cucumis sativus L. using
animal models. Our results suggest that the
whole fruit homogenate of Cucumis sativus L.
had anti-inflammatory activity and unlike
synthetic drugs, had no dose-dependent side
effects. This presents Cucumis sativus L. as a
functional food for the management of
inflammation.
CONSENT
It is not applicable.
ETHICAL APPROVAL
All experimental protocols including the use of
animal models were approved and followed the
guidelines of the Faculty of Biological Sciences
Ethical Committee of the University of Nigeria,
Nsukka, Nigeria.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
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