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Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2519
EVALUATION OF ANTI-INFLAMMATORY
ACTIVITY OF CILNIDIPINE IN ALBINO WISTAR
RATS
Satish AM1, Venu Dakshinamurthy2, Sai Chakith MR3, Ashwini
P4, Yesu Raju G5, Sushma Pradeep6, Shiva Prasad Kollur7*,
Chandan Shivamallu8*
Article History: Received: 16.05.2023 Revised: 26.06.2023 Accepted: 22.07.2023
Abstract
Inflammation is the response to injury of cells and body tissues from different factors such as infections,
chemicals, and thermal and mechanical injuries, inflammation plays a central role in various diseases.
Hence it is required to search for new anti-inflammatory drugs which can have lesser side effects and
there is a need to find out the anti-inflammatory effect of existing drugs that are predominately used for
diseases other than an inflammatory condition. In this study, we investigate the potential property of
Cilnidipine in inflammation suppression. The Carrageenan rat paw edema model is one of the acute
inflammatory models examined in the present investigation. The Cotton pellet-induced granuloma
model is a component of the chronic inflammatory model. Indomethacin was employed as the standard
medicine and the calcium channel blocker cilnidipine as the test drug in all experimental inflammatory
models. The test medication suppressed carrageenan-induced rat paw edema by 28%, but indomethacin
inhibited it by 47% compared to the control. The anti-edema activity of the test group was therefore
comparable to that of the standard. The calcium channel blocker cilnidipine had an anti-inflammatory
effect equivalent to that of the well-known drug indomethacin in a rat paw edema model brought on by
carrageenan. In comparison to the control group and the test group, indomethacin reduced the dry
granulation tissue weight produced by cotton pellets by 66% and 56%, respectively. Cilnidipine
showed a mild anti-granuloma effect in contrast to the standard drug. The calcium channel blocker
cilnidipine demonstrated a minor anti-inflammatory effect similar to that of the common drug
Indomethacin in the Cotton pellet-induced granuloma model. Cilnidipine demonstrated effective anti-
inflammatory effects in the carrageenan-induced paw edema model and the cotton pellet-induced
granuloma paradigm. The calcium channel blocker cilnidipine showed positive results in both the acute
and chronic forms of experimental inflammation, in contrast to regular Indomethacin. A calcium
channel-blocking drug like cilnidipine has an anti-inflammatory action by inhibiting the above-
mentioned mediators of inflammation. This is the likely mechanism for the acute anti-inflammatory
action of cilnidipine. The influx of calcium is an essential step in the release of histamine and serotonin
from mast cells and in the synthesis of prostaglandins.
Keywords: Cilnidipine; Carrageenan; Anti-inflammation; albino Wistar.
1,2,3,5Department of Pharmacology, JSS Medical College, JSS Academy of Higher Education &
Research, Mysuru, Karnataka.
4Department of Microbiology, JSS Academy of Higher Education & Research, Mysuru, Karnataka.
6,8*Department of Biotechnology & Bioinformatics, JSS Academy of Higher Education & Research,
Mysuru, Karnataka.
7*School of Physical Sciences, Amrita Vishwa Vidyapeetham, Mysuru, Karnataka.
*Corresponding author’s Email: 8*chandans@jssuni.edu.in, 7*shivachemist@gmail.com
DOI: 10.31838/ecb/2023.12.s2.397
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2520
1. Introduction
Any host defense mechanism's primary
tactic for dealing with or defeating an
encroaching infection or foreign object is
inflammation. Pain and inflammation are
the most frequent symptoms that patients
present to doctors with. Inflammation is a
typical defense response that involves a
complex network of the cell, cell-mediator,
and tissue interaction. Celsus was the first
to describe the signs of inflammation;
Galen and Hunter later added more
information. Some of them include Rubor
(Redness), Tumor (Swelling), Calor (Heat),
Dolor (Pain), and Functiolaesa (loss of
function). The exudation of the fluid and
aberrant build-up of various inflammatory
cells characterizes the majority of
inflammatory disorders. Prostaglandins,
leukotrienes, histamine, bradykinin,
cytokines, growth factors, neutrophil
lysosomal contents, reactive oxygen
species, etc. are examples of inflammatory
mediators that control this process [1].
Among the non-infectious diseases that are
characterized by the recruitment of
inflammatory mediators are chronic
obstructive pulmonary disease (COPD),
acute respiratory distress syndrome
(ARDS), autoimmune diseases like
Systemic lupus erythematosus (SLE),
rheumatoid arthritis (RA), dermatological
conditions like psoriasis and pemphigus,
inflammatory bowel diseases like Crohn's
disease and ulcerative colitis, among others
[2].
One of the body's special
defense mechanisms, inflammation aids in
the body's defense against unpleasant
stimuli such allergies, burns, poisonous
substances, and infections. However, the
body's overreaction could be dangerous or
unwanted. Generally speaking, the
inflammatory response serves to protect the
host (e.g., by localizing abscesses and
reducing bacterial and viral loads), but it
frequently goes unregulated and causes
tissue damage, which results in a variety of
inflammatory illnesses (like Rheumatoid
arthritis). In these circumstances, the use of
pharmacological therapy to reduce or
eliminate the unwelcome inflammatory
response is necessary. Although
inflammation is the common denominator,
it manifests itself in different ways;
therefore, each inflammatory condition
requires a different strategy for therapy [3].
In addition to being able to regulate
inflammation, an anti-inflammatory drug
should be able to lessen the effects of
persistent inflammation (like the formation
of fibrous adhesion bands following
peritonitis and joint deformities in
Rheumatoid arthritis).
An anti-inflammatory agent is a substance
that lessens one or more features of the
inflammatory process. The medications
used will have a heterogeneous structure, a
variety of mechanisms of action, and a
range of effectiveness because
inflammation is a complex process. In
addition to their anti-inflammatory
properties, they may also have antipyretic
and analgesic properties, which make them
helpful in the treatment of diseases where
fever and pain are correlated with the
severity of the inflammatory process. Anti-
inflammatory drugs can thereby reduce
pain in inflammatory clinical settings. For a
very long time, inflammatory therapy has
been debatable and unfinished. The
introduction of sodium salicylate,
acetylsalicylic acid (ASPIRIN), cortisone,
gold salts, and phenylbutazone for the
treatment of inflammatory disorders, as
well as the development of clinically
effective anti-inflammatory medications
like selective COX-2 inhibitors,
Oxyprofen, aceclofenac, and others,
represent important advancements. The
current top three categories of anti-
inflammatory drugs include
glucocorticoids, disease-modifying anti-
rheumatic drugs, and NSAIDs (DMARDs)
[5].
The mainstay of anti-inflammatory
medications consists of both more recent
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2521
medications like selective COX-2
inhibitors, Oxyprofen, aceclofenac, and
salicylates that were accidentally
introduced into clinical medicine3 and older
ones like salicylates, paracetamol,
cortisone, gold salts, and phenylbutazone.
NSAIDs, glucocorticoids, and disease-
modifying anti-rheumatic medicines are the
three main categories of anti-inflammatory
medications that are now in use
(DMARDs).
NSAIDs work by inhibiting the COX
enzyme, which thereby prevents the
production of prostaglandins.
Glucocorticoids are potent anti-
inflammatory drugs because they inhibit the
Phosholipase-A2 enzyme, which blocks the
COX and LOX pathways and, in turn,
prevents the production of prostaglandins
and leukotrienes [6]. Contrary to gold salts,
leflunomide, chloroquine, anakinra, and IL-
1 receptor antagonist for rheumatoid
arthritis4 and Diacerein for osteoarthritis,
DMARDs are rarely used to treat
inflammation. Instead, they are only
employed to treat a certain inflammatory
illness [7].
Currently available anti-inflammatory
medications have disadvantages and are
associated with unfavourable ide effects. In
34–46% of NSAID users, it is assumed that
the reduction of the protective COX
enzyme in the stomach mucosa results in
some gastrointestinal damage 5. Although
recently developed selective COX-2
inhibitors may be easy on the stomach, they
may also have a prothrombotic propensity
that increases the risk of MI and mortality.
A variety of adverse effects are also brought
on by the continuous treatment of
glucocorticoids.
Based on a better understanding of the
function of inflammatory mediators, which
have been identified as the primary causes
of inflammation, efforts are being made to
create novel, safer, and more effective anti-
inflammatory medications [8]. The design
and synthesis of NSAIDs fused to NO is
one of the most recent advancements in the
field of anti-inflammatory medications now
being tested. Ibuprofen and naproxen are
examples of traditional NSAIDs with NO-
donating groups that release NO after being
hydrolyzed in the stomach and are linked to
a lower incidence of ulcerogenic events and
an enhanced anti-inflammatory profile.
Other methods include controlling or
suppressing arachidonic acid metabolite
formation, reducing the development or
activity of lipoxygenase, as in the case of
the leukotriene receptor antagonist
Montelukast, and combining standard
NSAIDs with Misoprostol (PGE1) [9].
Leukocyte trafficking inhibitors have
received a lot of attention, and studies into
the integrins, selectins and other adhesion
molecules that are involved in the targeting
and transmigration of blood leukocytes are
now being conducted. The monoclonal
antibody method has been applied to
several numbers of potential substances.
For the treatment of psoriasis, efalizumab,
which binds the CD11a adhesion molecule,
has received approval. A very late antigen
(VLA)-4 is a different adhesion molecule
that Natalizumab targets to stop
lymphocytes from focusing on multiple
sclerosis plaques [10]. A brand-new class of
drugs called COX-3 antagonists, CGRP
antagonists, N-Acetylcholine receptor
antagonists, Vallinoid7, and Neurokinin
receptor antagonists is being created to treat
pain and inflammation. Older drugs are
now being used in novel ways, such as the
anti-malarial drug chloroquine, which was
previously used to treat rheumatoid
arthritis. Recently, we have begun to
demonstrate the anti-inflammatory
properties of additional classes of
medicines that are not often classified as
anti-inflammatory drugs [10, 11].
In contrast to most calcium antagonists,
cilnidipine can also affect sympathetic
nerve endings' N-type calcium channels in
addition to L-type calcium channels, which
is how most calcium antagonists’ work. It
provides more benefits than standard
calcium-channel blockers due to its N-type
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2522
calcium-channel blocking abilities6. One of
the main side effects of conventional
calcium channel blockers, Pedal edema, is
less common with this drug. The release of
histamine and serotonin from mast cells as
well as the production of prostaglandins
depends on a calcium influx. Therefore, we
anticipate that by reducing the
aforementioned inflammatory mediators,
calcium channel-blocking medications like
cilnidipine will have an anti-inflammatory
effect. Hence an earnest attempt is being
made in this study to explore the anti-
inflammatory activity of cilnidipine [12].
2. Materials and Methods
In this study, the calcium channel blocking
drug cilnidipine has been taken up for the
investigation of anti-inflammatory activity.
A well-known and well-recognized
member of the NSAIDS family of anti-
inflammatory drugs, indomethacin was
taken routinely. Carrageenan, red seaweed,
and 1% gum acacia were employed to
create edema. From the central animal
facility at the J.S.S. Medical College in
Mysore, adult healthy albino rats of the
Wistar strain were chosen. They should
have identical traits and weigh between 150
and 250 g. The tools utilized in the
experiment include a tuberculin syringe,
cotton wool pellets, screw gauge, mercury
plethysmograph, skin suturing kit, mouth
gag, and electronic balance.
Acute Inflammatory Models
Carrageenan Induced Rat Paw Edema
Model in Rats
The method adopted here involves the
examination of the inflammatory reaction
generated by the phlogistic agent
carrageenan injected into the subplantar
surface of the rat's hind paw. A Mercury
plethysmograph80 was used in this
investigation to record paw edema. We
used albino rats with the same
characteristics, either sex or weighing 150–
250 grams. The animals were divided into
four groups of six each. The first group
served as a control that wasn't given any
treatment, the second served as a
benchmark, and the final two served as test
groups. The untreated control group
received an oral dose of 1% gum acacia.
The standard group received 10mg/kg of
indomethacin diluted in distilled water,
while the test group received 200mg/kg of
an aqueous extract of fenugreek seeds
suspended in 1% gum acacia. Before the
carrageenan injection, all medications were
given orally one hour beforehand [13, 14].
Throughout the trial, neither food nor water
was given to the animals. Every time, the
same anatomical landmark was recorded at
the same spot. One hour after gum acacia
was given to each test group; 0.05ml of 1%
carrageenan was sub-plantarly injected into
a rat's right hind paw. The Mercury
plethysmograph was used to measure the
right hind paw volume instantly (0-hour-
volume), with the end of 4hours revealing
the actual edema. Comparing the mean paw
edema in animals given various
medications group-wise to the untreated
control group [15].
The percent inhibition of edema = vc-vt
/vc×100
Where Vc = Mean paw edema volume
in the control group.
Vt = mean paw edema volume
in the drug treated group.
Chronic Inflammatory Model.
Cotton Wool Pellet Granuloma in Rats
The approach of Meir R et al, 1950 was
used in this work to examine the chronic
inflammatory response brought on by
subcutaneous cotton pellet implantation in
rats.
We employed four sets of six albino rats,
each weighing between 150 and 250 g,
either sex. The first group functioned as the
untreated control, the second as the
Standard, and the other two as the test
groups [14, 15].
In the untreated control group, 1% gum
acacia was administered orally. The
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2523
reference group was given 10 mg/kg of
indomethacin dissolved in distilled water,
while the test group was given 200 mg/kg
of aqueous fenugreek seed extract in 1%
gum acacia. All drugs were given orally on
the first day, one hour before the
application of the cotton pellets. These were
then consumed orally once daily for the
following six days. After giving the rats a
brief ether anesthesia, 1 cm long linear
incisions were made in each axilla and
groin under aseptic circumstances. These
sites received four implantations of sterile
cotton wool pellets weighing 10 mg each,
followed by aseptic closure of the incisions
with black silk thread. The animals were
kept in clean cages during the trial and
given food and water. Following their
removal from the animal, the cotton pellets
with granulation tissue were cleaned of any
extraneous tissue and dried in a hot air oven
to constant weight before the animal was
killed later on the eighth day. It was feasible
to calculate the dry weight of the granuloma
by calculating the difference between the
cotton pellets' measured dry weights before
and after implantation (i.e., the volume of
genuine granulation tissue generated) [16,
17].
Percent anti-granuloma activity = wc-wt
/wc×100
Where, Wt= mean dry weight of granuloma in drug treated group
Wc= mean dry weight of granuloma in drug untreated control group.
(a) (b) (c)
Figure 1: (a) Mercury Plethysmograph, (b) Carrageenan induced rat paw edema model and
(c) Cotton pellet induced granuloma model.
3. Results
Statistical methods applied
The descriptive method produces standard
values and presents univariate summary
statistics for a number of variables in a
single table (z scores). The order of the
variables you choose, their magnitude, or
their alphabetical order can all be used to
arrange the data (in ascending or decreasing
order).
With the use of a single factor
(independent) variable, a one-way ANOVA
method is used to create a one-way analysis
of variance for a quantitative dependent
variable. The multiple means hypothesis is
evaluated for equality using analysis of
variance. With this approach, the two-
sample t-test is lengthened.
Bonferroni Post hoc test
Once it has been established that there are
differences among the means, post hoc
range tests and pairwise multiple
comparisons can be performed to determine
which means are different. Range analyses
reveal homogeneous groupings of means
that are identical to one another. Pairwise
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2524
multiple comparisons, which compare the
differences between each pair of means,
result in a matrix with asterisks designating
group means that are significantly different
from one another at an alpha level of 0.05.
One of the often-used post hoc tests in the
medical sciences is the Bonferroni test. The
SPSS for Windows programme was used to
conduct all of the statistical analyses
(version 21.0)
Carrageenin -induced rat paw edema
method
Table 1: Table displaying the average rat paw volume (in cm) for each medication group at 0
and 4 hours.
Time
N
Group
Mean (SD)
F
*p-value
0 hr
6
Ctrl
0.67(0.16)
0.621
0.551
6
Std
0.6(0.09)
6
cilnidipine
0.58(0.15)
1 hr
6
Ctrl
1(0.21)
3.43
0.059
6
Std
0.75(0.14)
6
cilnidipine
0.9(0.14)
2 hr
6
Ctrl
1.37(0.38)
4.162
0.036
6
Std
0.97
6
cilnidipine
1.08(0.12)
*ANOVA test
An analysis of variance showed that the
effect of cilnidipine was significant,
F(2,15) = 4.162, p – value = 0.036. The post
hoc test using the Bonferroni post hoc
criterion for significance indicated that the
mean values of the standard drug were
significantly different from the test drug.
Ctrl: Control-2%gum acacia (2g in 100 ml
of distilled water), Std: Standard-
Indomethacin (10mg/kg) and Test:
cilnidipine (1.5mg/kg).
Figure 2: The graph shows the mean rat paw volume at 0hr, 1hr, and 2hr in the control
group. Rat paw volume is measured by the Mercury plethysmograph method.
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2525
Figure 3: The graph shows the mean rat paw volume at 0hr, 1hr, and 2hr in the standard
group. Rat paw volume is measured by the Mercury plethysmograph method.
Figure 4: The graph shows the mean rat paw volume at 0hr, 1hr, and 2hr in the test group. Rat
paw volume is measured by the Mercury plethysmograph method.
The mean paw volume in the control group was 0.67 cm at 0 hours, 1 cm at 1 hour, and 1.37
cm at 2 hours, indicating the maximum increase in mean paw volume edema, signifying the
maximum inflammation. A mean paw volume of 0.6 cm at 0 hours, 0.75 cm at 1 hour, and 0.97
cm at 2 hours in the standard group receiving indomethacin indicated good anti-inflammatory
activity. Clevidipine treatment in the test group resulted in mean paw volumes of 0.58 cm at 0
hours, 0.9 cm at 1 hour, and 1.08 cm at 2 hours. This demonstrates that under experimental
conditions, the test group's increase in paw volume edema was almost identical to that of the
Standard group. This indicates that the test medicine has effective anti-inflammatory efficacy
relative to the current model's standard.
Below Tables depicting the Carrageenan-induced rat paw edema model. Also, they are showing
the mean difference in rat paw volume (cm) in different drug groups.
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2526
Table 2: Independent samples t test.
After 1 hr
N
Mean
p-value*
Control
6
1.0(0.20)
0.035
Standard
6
.750(0.14)
Control
Test
1.0(0.20)
0.90(0.14)
0.356
There is a significant difference between test and control and standard and control groups after
1 hr.
Table 3: Independent samples t test.
After 4 hr.
N
Mean
p-value*
Control
6
1.37(0.38)
0.039
Standard
6
.967(0.16)
Control
Test
1.08(0.12)
1.37(0.38)
0.110
The difference between the control and the
standard is considerable, but not the
difference between the control and the test.
Ctrl: Control 2%gum acacia (2g/100ml of
distilled water), Std: Standard-
Indomethacin (10mg/kg) and Test:
cilnidipine (1.5mg/kg).
Table 4: By taking the percentage inhibition of the control group as 0%, the table below
shows the mean percentage inhibition of paw edema in the carrageenan-induced rat paw
edema model in several groups.
Control
0%
Standard
47%
Test
28%
Figure 5: Percent inhibition of paw edema in different groups in considering the percent
inhibition by the control as 0%.
Standard showed a 47% inhibition of paw
edema while cilnidipine showed a 28%
inhibition. As a result, the test group's anti-
edema activity was comparable to that of
the standard. Cotton wool pellet induced -
granuloma model
0
47.14
28.57
0
10
20
30
40
50
Control Standard Test
Mean dry granulation
tissue in MGS
Groups
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2527
Table 5: The average weight of dried granulation tissue across various medication classes
Groups
Mean(SD)
F
p-value*
Control after weight
20 (1.09)
39.26
< .000
Standard after weight
14.67 (0.82)
Test after weight
16.5 (1.22)
*One-way ANOVA
An analysis of variance showed that the
effect of cilnidipine was significant,
F(2,15) = 39.26, p < .000.
The post hoc test using the Bonferroni post
hoc criterion for significance indicated that
the mean values of all three groups are
significantly different from the other
groups. Ctrl: Control-2%gum acacia (2g in
100 ml of distilled water), Std: Standard-
Indomethacin (100mg/kg) and Test:
cilnidipine (1.5mg/kg).
Figure 6: mean dry granulation tissue in different groups in (mgs) Cotton pellet induced
granuloma.
The maximum dry granuloma weight in the
control group was 20 mg, demonstrating the
highest levels of granuloma development
and inflammation. The minimal dry
granuloma weight of 14.67 mg in the
control group indicated maximum anti-
granuloma activity and minimal granuloma
formation. Cilnidipine-treated test groups
revealed 16.5 mg of granuloma weight.
Therefore, under the current experimental
setup, cilnidipine's anti-granuloma activity
was of a moderate degree compared to the
Standard.
Table 6: Independent t test (Cotton pellet induced granuloma model).
After weight
Mean (SD)
t
p-value*
Control
Standard
20(1.09)
14.67(0.82)
9.562
<.000
Control
Test
20(1.09)
16.5(1.22)
5.217
<.000
The mean of control after weight and
standard after weight as well as the mean of control after weight and test after weight is
statistically significantly different.
20
14.67 16.5
0
5
10
15
20
25
control standard test
Mean dry granulation
tissue in MGS
Groups
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2528
Table 7: Mean percent inhibition of dry granulation tissue weight considering percentage
inhibition of control as 0%.
Control
0%
Standard
66%
Test
56%
Figure 7: Mean percent inhibition of dry granulation tissue weight considering the percentage
inhibition of control as 0%.
Granuloma weight was inhibited by
standard to a percentage of 66% and by
calcium channel blocker cilnidipine to a
percentage of 56%. As a result, in the
current experimental setup, the anti-
granuloma activity of the calcium channel
blocker cilnidipine was of a modest degree
when compared to the standard.
4. Discussion
Inflammation is a crucial part of the body's
defense mechanism. Acute inflammation is
characterized by vasodilatation, plasma
exudation, the generation of
several inflammatory mediators, cytokines,
growth factors, and leukocyte emigration.
Chronic inflammation is characterized by
increased connective tissue growth,
fibroblast and blood vessel proliferation,
and mononuclear cell infiltration. Tissue
infection is the paradigm of an
inflammatory response. Anti-inflammatory
drugs work at several stages to reduce
inflammation.
When given to spontaneously hypertensive
rats, cilnidipine was found to suppress the
pressor response brought on by acute cold
stress in addition to having a hypotensive
effect (SHRs).
In light of the aforementioned facts, the
anti-inflammatory capability of the calcium
channel blocker cilnidipine has been
examined in this study, and it has been
compared to the industry-standard
reference medication Indomethacin.
The Carrageenan rat paw edema model is
one of the acute experimental inflammatory
models examined in the current
investigation. The Cotton pellet-induced
granuloma model is a component of the
chronic inflammatory model. Indomethacin
was employed as the standard medicine and
the calcium channel blocker cilnidipine as
the test drug in all experimental
inflammatory models.
Carrageenan-induced rat paw edema was
decreased by indomethacin by 47% and the
test medication by 28% when compared to
the control. As a consequence, the anti-
edema activity of the test group was
comparable to that of the reference group.
As a result, the calcium channel blocker
cilnidipine showed a significant anti-
inflammatory effect comparable to the
over-the-counter drug Indomethacin in the
0
66.62
56.25
0
10
20
30
40
50
60
70
Control Standard Test
Mean dry granulation
tissue in MGS
Axis Title
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2529
Carrageenan-induced rat paw
edema model.
In comparison to the control group and the
test group, indomethacin reduced the dry
granulation tissue weight produced by
cotton pellets by 66% and 56%,
respectively.
Comparing cilnidipine to the conventional
medication, the anti-granuloma impact was
mild. Cilnidipine, a calcium channel
blocker, demonstrated this. Moderate anti-
inflammatory activity in the cotton pellet-
induced granuloma model, comparable to
the common drug indomethacin.
Cilnidipine demonstrated effective anti-
inflammatory effects in the carrageenan-
induced paw edema model and the cotton
pellet-induced granuloma paradigm.
The calcium channel blocker cilnidipine
showed promising results in both the acute
model of experimental inflammation and
the chronic type of experimental
inflammation when compared to the
conventional Indomethacin in the current
study.
The reduction of prostaglandin synthesis by
cilnidipine may be the likely mechanism for
its acute anti-inflammatory effects. The
production of prostaglandins and the
release of histamine and serotonin from
mast cells both depend on the calcium
influx. Therefore, cilnidipine, a calcium
channel-blocking medication, has an anti-
inflammatory effect by decreasing the
inflammatory mediators.
Clinical studies by Rose and Ikebukoro,
who showed that cilnidipine, which is like
the angiotensin-converting enzyme
inhibitor benazepril, significantly
decreased urinary albumin excretion
without affecting serum creatinine
concentration in hypertensive patients, are
another study that supports the validity of
the present one.
Other inflammation-related measures, such
as erythema, discomfort, etc., require the
use of different assays. As it is impossible
to directly extrapolate human data from
animal data, more research is necessary to
support these conclusions in humans.
So, during the administration period, the
calcium channel blocker cilnidipine may be
used alone or in combination with other
widely used anti-inflammatory drugs such
NSAIDs, steroids, LT receptor antagonists,
mast cell stabilizers, cytotoxic therapies,
cytokine modulators, etc.
5. Conclusion
Every material found in nature has some
sort of therapeutic value. Different plant
sections have various medicinal effects. To
achieve the greatest results, the proper part
must be purchased. Numerous
investigations on cilnidipine have revealed
that in people with mild to
moderate essential hypertension, it is
efficient as a once-daily antihypertensive
medication and has little effect on heart rate
and the autonomic nervous system.
Additionally, it is hypothesized that
cilnidipine has other advantages including
the suppression of the pressure response
brought on by acute cold stress. Contrasting
with the usual Indomethacin in the current
investigation, the calcium channel blocker
cilnidipine showed good anti-inflammatory
action in acute models and modest activity
in a chronic model of inflammation.
Cilnidipine has anti-inflammatory
properties because it inhibits the formation
of mediators that cause inflammation, such
as histamine and serotonin, prostaglandins,
myeloperoxidases, cyclooxygenase, NO
inhibition, inducible nitric oxide synthase
protein, antioxidant effects, etc.
The current study hypothesized that using
cilnidipine as monotherapy or in
combination with other prescription drugs
may have the extra benefit of having anti-
inflammatory effects in a variety of
inflammatory illnesses. These studies help
identify potential anti-inflammatory drug
lead compounds while keeping in mind the
drawbacks of NSAIDs and corticosteroids.
Additional studies in a variety of other
Section A-Research paper
Evaluation of Anti-Inflammatory Activity of Cilnidipine
in Albino Wistar Rats
Eur. Chem. Bull. 2023, 12 (S2), 2519 – 2532 2530
acute and chronic inflammatory models, in
addition to human studies, are required to
support the findings and demonstrate the
effectiveness of long-term administration
of the calcium channel blocker cilnidipine
as a potential anti-inflammatory agent in
routine clinical practice. The results of the
study showed that cilnidipine has a good
anti-inflammatory action in both the acute
and chronic models investigated when
compared to the reference drug
indomethacin. It may be said that
cilnidipine is a promising add-on anti-
inflammatory agent because it
demonstrated significant anti-inflammatory
activity in the models examined.
Acknowledgement
Authors thank the Leadership of JSS AHER
for providing the infrastructure support.
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