Indo American Journal of Pharmaceutical Research, 2014

ISSN NO: 2231-6876

ANTINOCICEPTIVE EFFECT OF ETHANOLIC FLOWER EXTRACT OF ACALYPHA

WILKESIANA PLANT
Moka.Abhinaya*, K.Ravi Shankar, G.V.N Kiranmyi
Dept. of. Pharmacology, Sri Sai Aditya Institute of Pharmaceutical Sciences and Research, affiliated to Andhra university, ,India.
ARTICLE INFO
Article history
Received 03/11/2014
Available online
16/12/2014

Keywords
Acalypha Wilkesiana,
Analgesic,
Anti-Inflammatory,
Carrageenan,
Tramadol,
Diclofenac sodium.

ABSTRACT
The flowers of Acalypha wilkesiana are commonly used for the treatment of pain, fever and
ulcer by traditional medical practitioners without any scientific data to evaluate the
appropriateness of some of the practices. Therefore this present investigation was carried out
to evaluate the ethanolic extract of flowers of Acalypha wilkesiana for analgesic and antiinflammatory activities using different models of pain and inflammation. The hot plate
latency assay, eddys hot plate method using analgesiometer in albino rats, acetic acid
induced writhing responses in mice models were used to evaluate analgesic effects. Animals
were divided into four groups. Control (administered saline) and reference (administered
Tramadol and Diclofenac sodium) groups, Comprising of 3 rats each. Flower extract groups
administered 100 and 200 mg/kg body weight of extract. Inflammation was induced using
Carrageenan in the left hind paw in the planar tissue. The Anti inflammatory activity was
carried out using Carrageenan induced paw oedema in rats, protein denaturation and HRBC
(human red blood cells) membrane stabilization assay (Invitro test). Tramadol and Diclofenac
sodium were used as standard drugs for analgesic and anti-inflammatory activity respectively.
The results show that the extract produced dose dependent and significant (p<0.05) analgesic
and anti inflammatory activities. This study has therefore further provides evidence that may
support the ethno medicinal uses of the ethanolic extracts of Acalypha wilkesiana flowers.

Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Please cite this article in press as Moka Abhinaya et al. Antinociceptive Effect of Ethanolic Flower Extract of Acalypha
Wilkesiana Plant. Indo American Journal of Pharm Research.2014:4(12).

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Corresponding author
Moka Abhinaya
Sri Sai Aditya Institute of Pharmaceutical Sciences and Research,
Affiliated to Andhra University,
abhinaya39pharma@gmail.com,
9573987892

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INTRODUCTION
Acalypha wilkesiana (family: euphorbiaceae) is an ornamental plant that is used commonly for hedging in west Africa and
indeed many parts of the world[1]. The plant is generally referred to as copper leaf and it is a shrub with mostly glossy green or red
leaves. The leaves of A.wilkesiana have variety of ethno medicinal uses which includes treatment of gastrointestinal disorders and skin
infections. It also has antibacterial, antifungal, immunomodulatory and antimalarial effects [2][3]. The flowers of the plant have been
reported to be rich in alkaloids, tannins, saponinns, anthraquinones, triterpenoids, sesquiterpenoids, carbohydrates, flavanoids,
glycosides, proteins, steroids and polyphenols.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in
terms of such damage [4].Pain motivates the individual to withdraw from damaging situations to protect a damaged body part while it
heals and to avoid similar experiences in the future [5].
Inflammation is pathophysiological response of a living tissue to injuries that leads to the local accumulation of fluid and
blood cells. Although it is a defense mechanism that helps body to protect itself against infection, burn, toxic chemicals, allergens or
other noxious stimuli. The complex events and mediators involved in the inflammatory reaction can be induced, maintain, or
aggravate many diseases [6]. Studies have been continuing on inflammatory diseases and the side effects of the currently available anti
inflammatory drugs poses a major problem during their clinical use. Therefore, development of newer and more powerful anti
inflammatory drugs with lesser side effects is necessary.
No pharmacological work has been reported on the flower extract of this plant hence the research study was taken by the
author to evaluate their biological activities. The focus of the present work is to investigate the analgesic and anti inflammatory effects
of the flower extract in laboratory animals.
MATERIALS AND METHODS
Preparation of plant extract
The flowers of Acalypha wilkesiana were collected at Sri Sai Aditya Institute of Pharmaceutical Science and Research
college premises, Surampalem, East Godavari district of Andhra Pradesh, India in the month of February 2014 .The flowers of the
plant were air dried reduced to powder and was extracted with ethanol. The dark brown solid extract obtained was dried in a
dessicator.
Experimental/ Methodology
Experimental animals
Albino rats of (150-200g) and Swiss albino mice (75-100g) of either sex were used in the entire study. They were housed in
standard polypropylene cages and were maintained in standard environmental conditions of temperature (24C), humidity (60-70%)
and light dark cycle (12 hr). The animals were fed with standard laboratory diet and water. Food was withdrawn 12 hrs before and
during the experimental hours.
Animal grouping:
In the analgesic and anti inflammatory studies animals were divided into 4 groups each comprising of 3 animals .Group. I
received normal saline (control).Group.II received standard reference drug. Group.III received Acalypha wilkesiana plant flower
extract (100mg/kg).Group.IV received Acalypha wilkesiana plant flower extract (200mg/kg).saline and drug extract was administered
through the oral route.
Evaluation of Analgesic activity of Acalypha Wilkesiana flower extract:
Tail flick method using hot plate:
In this method adult albino rats of either sex were selected. The basal reaction time to radiant heat by placing the tip of the
tail on the radiant heat source was recorded using stopwatch. The basal reaction time was observed at 0, 15, 30, 60, 120 mins, the
analgesic effect of ethanolic flower extract was assessed using this method.

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Acetic acid induced writhing responses in mice:

In this method albino mice were selected. Animals were injected 0.1ml of 1% acetic acid solution intraperitoneally. The
numbers of writhes (stretching of abdomen with simultaneous stretching of atleast one hind limb) are recorded for each animal. The
change in number of writhing in test group was compared with standard treated and control treated groups was observed. The writhing
movements were observed and recorded after acetic acid administration [8].

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Eddys hot plate method:

In this method adult albino rats of either sex were selected. The animals were placed individually on the hot plate maintained
between 550c. The time taken for each rat to respond to the thermal stimulus by paw licking and jumping off the hot plate was
recorded. The reaction time was observed at 0, 15, 30, 60,120 min. The anti nociceptive effect of ethanolic flower extract was assessed
using this method [7].

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Evaluation of Anti Inflammatory activity of Acalypha wilkesiana flower extract

In vivo method:
Carrageenan induced paw oedema in rats:
Carrageenan was used to induce oedema in this study. The animals were pretreated with ethanolic extract (100 mg/kg and
200 mg/kg) suspended in 2%acacia, animals received Diclofenac sodium (10mg/kg) After 30 min 0.1ml of 1%w/v suspension of
Carrageenan in distilled water was injected subcutaneously on to the sub plantar region of the left hind paw of the animals.
Measurement of paw size was carried out by wrapping a piece of cotton thread round the paw and measured using plythesmometer.
Paw sizes were measured immediately before and 1 hr after Carrageenan [9] injection. Oedema inhibitory activity was calculated using
the following formula.
% inhibition = (1- vt/vc) 100
Whereas vt = oedema volume of control animal
Vc = oedema volume of treated animal
Invitro methods:
Protein denaturation method [10][11]:
Test solution (0.5ml) consists of 0.45ml of Bovine serum albumin (5% w/v aqueous solution) and 0.05ml of test samples of
different concentrations (100mg/ml and 200mg/ml).Test control solution (0.5ml) consists of 0.45mlof bovine serum albumin (5% w/v
aqueous solution) and 0.05ml of distilled water. Product control solution (0.5ml) consists of 0.45ml of distilled water and 0.05ml of
test samples of different concentrations ( 100mg/ml and 200 mg/ml).Standard solution (0.5ml) consists of 0.45ml of Bovine ser um
albumin (5% w/v aqueous solution) and 0.05ml of different concentrations (10mg/ml, 25mg/ml) of Diclofenac sodium. All the above
solutions were adjusted to pH 6.3 using 1N hydrochloric acid. The samples were incubated at 37 o C for 20 min and the temperature
was increased to keep the sample at 57 degree C for 3 min. After cooling, 2.5ml of phosphate buffer was added to the above solution.
The absorbance was measured using UV visible spectrophotometer at 416nm.the percentage inhibition of protein denaturation was
calculated as,
% Inhibition of protein denaturation=100-[{(O.D of test solution O.D of product control)/O.D of test control}*100]
The control represents 100% protein denaturation. The results were compared with Diclofenac sodium
HRBC membrane stabilization method:
Blood was collected from the healthy volunteers and mixed with equal volume of sterilized alsever solution (2% dextrose,
0.8% sodium citrate, 0.05% citric acid, 0.42% sodium chloride in water). The blood was centrifuged at 3000 rpm and packed cells
were washed with isosaline (0.85%, pH 7.2) and a suspension was made with isosaline (10%w/v). The assay mixture contained 1ml of
phosphate buffer (0.15M, Ph 7.4), 2ml of hyposaline (0.36%), and 0.5ml of HRBC suspension and 1ml of various concentrations o f
the extract. Diclofenac sodium was used as a standard drug. In the control solution instead of hyposaline 2ml of distilled water was
added. The mixtures were incubated at 37C or 30 min and centrifuged. The absorbance of the supernatant solution was read at
560nm.the percentage heamolysis was calculated by assuming the heamolysis produced in the presence of distilled water as 100%[12].
The percentage of HRBC membrane stabilization or protection was calculated using the formula

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RESULTS AND DISCUSSION

No toxicity or death was observed in the experimental mice. The present study investigated the analgesic and anti
inflammatory effects of an ethanolic extract of Acalypha wilkesiana flowers in rats. In the analgesic study the extract produced
significant analgesic effects in the 3 models of pain employed.
In tail flick method, rats on treatment with ethanolic flower extract of Acalypha wilkesiana (100mg/kg and 200mg/kg orally)
significantly inhibited noceception in rats at 30 min by 29.70% and 44.40% respectively. Where as Paracetmol (500mg/kg)
significantly inhibited pain perception at 60 min by 78% (p<0.001).
In eddys hot plate method, rats on treatment with ethanolic flower extract of Acalypha wilkesiana (100mg/kg and 200mg/kg
orally) significantly inhibited nociception in rats at 30 min by 52% and 67% respectively. Whereas Tramadol (5mg/kg) significantly
inhibited pain perception at 60 min by 78% (p<0.001).
In rats using acetic acid induced writhing responses. It was observed that mice treated with ethanolic flower extract 100
mg/kg (42.40%) and 200 mg/kg (65.80%) shows significant protection compared to control group. Tramadol showed 93.97%
protection against acetic acid induced writhing in mice.
Maximum percentage of inhibition 69.1% at 200mg/ml
was observed from ethanolic flower extract of Acalypha
wilkesiana by protein denaturation method and Diclofenac sodium showed the maximum inhibition 80.4 at 25mg/ml concentration.
Invitro anti inflammatory effect of ethanolic flower extract of Acalypha wilkesiana by HRBC membrane stabilization
method. Ethanolic flower extract of Acalypha wilkesiana prevent hypotonicity induced membrane lysis (HRBC membrane
stabilization method) to an extent of 58.30% at the concentration of 200 mg/ml which is comparable to that of the standard drug
Diclofenac sodium 68.30% (25 mg/ml). The anti inflammatory activity of the extract was concentration dependent

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% membrane stabilization = 100-(O.D of test solution O.D of product control)*100

O.D of test control

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In vivo anti inflammatory effect of ethanolic flower extract of Acalypha wilkesiana in Carrageenan induced paw oedema in
rats, it was observed that rats treated with ethanolic flower extract at 100 mg/kg and 200 mg/kg showed significant anti inflammatory
activity and caused a significant inhibition in the percentage increase Carrageenan induced rat paw oedema the activity is compared
with standard Diclofenac sodium
Table 1: Effect of Ethanolic extract of Acalypha wilkesiana flower extract in rats using tail flick method.
Treatment group
Paracetmol 500mg/kg
Flower
100mg/kg
Flower
200mg/kg

extract
extract

0 min
B.R.T
7 0.5

-------

15 min
B.R.T
9.33

0.33
8.5 0.86

---------

8.5 0.28

% inh
------

6.5

0.28
6 0.0

%inh
63.60
23.50
31.70

30 min
B.R.T
17.33

2.84
9.25 0.72
10.45
0.31

29.70

60 min
B.R.T
9.33

2.90
7.5 0.28

44.40

7.5 1.44

%inh
74.10

%inh
56.70
13.30
22.60

120 min
B.R.T
6 0.57
6.8
0.34
6.3
0.75

%inh
33.30

4.41

7.93

B.R.T = basal reaction time

Table 2: Effect of Ethanolic flower extract of Acalypha wilkesiana in rats using eddys hot plate method.
Treatment group

0 min
R.T
7.12
0.11
10.5
0.28
11.75
0.43

15 min
30min
60min
120 min
180 min
R.T
%Inh R.T
%Inh R.T
%Inh R.T
%Inh R.T
%Inh
Tramadol
10.6 48.87 12.2 71.06 12.7 78.51 12.08 69.66 11.02 54.7
(5mg/kg)
0.1
.91
.75
1.6
0.9
Flower
extract
------- 15.75 33
22 52
13.75 23
12.25 14
11
10
(100mg/kg)
0.72
0.57
0.43
0.43
0.28
Flower
extract
------- 17.75 33
36.5 67
20
41.25 15.25 22
12.75 7.84
(200mg/kg)
0.43
0.28
0.57
0.14
0.14
R.T = reaction time
Table 3: Effect of Ethanolic flower extract of Acalypha wilkesiana in rats using acetic acid induced writhing responses.
%inh
-------

treatment
Control
Tramadol (5mg/kg)
Flower extract (100mg/kg)
Flower extract (200mg/kg)

Number of writhing
83 1.45
5 0.57
32.5 1.44
20.5 0.28

% inhibition
---------93.97
42.40
65.80

Table.4: In vitro Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana by protein denaturation method.
s.no

concentration

1
2
3
4

10 mg/ml
25 mg/ml
100 mg/ml
200 mg/ml

% inhibition
Flower extract
-----

Diclofenac sodium
74.7
80.4

45.52
69.1

s.no

concentration

1
2
3
4

10 mg/ml
25 mg/ml
100 mg/ml
200 mg/mi

% membrane lysis
Flower extract Diclofenac sodium
-----61.60
-----68.30
33
58.30

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Table.5: Invitro Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana by HRBC membrane stabilization
method.

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Table.6: In vivo Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana in Carrageenan induced paw
oedema in rats.
treatment
Control
Diclofenac sodium(10mg/kg)
Flower extract(100mg/kg)

Flower extract (200mg/kg)

Mean increase in paw diameter mm

O hr
1 hr
2 hr
3rd hr
0.34 0.01 0.52 0.04 0.91 0.02 1.2 0.17
0.26 0.13 0.3 0.01
0.46 0.02 0.58 0.01
42.30%
49.40%
51.82%
3.25 0.43 4 0.28
4.8 0.69
3.25 0.14
67.8%
25%
50%
2.35 0.20 4.05 0.28 5.03 0.20 3.25 0.14
53%
77%
30%

4th hr
0.86 0.017
0.3 0.029
66%
3.1 0.05
25%
3 0.173
29%

Fig. 1: Effect of Ethanolic extract of Acalypha wilkesiana flower extract in rats using tail flick method.

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Fig 2: Effect of Ethanolic flower extract of Acalypha wilkesiana in rats using eddys hot plate method.

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Fig 3: Effect of Ethanolic flower extract of Acalypha wilkesiana in rats using acetic acid induced writhing responses.

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Fig .5: Invitro Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana by HRBC membrane stabilization
method.

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Fig .4: In vitro Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana by protein denaturation method.

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Fig .6: In vivo Anti inflammatory effect of Ethanolic flower extract of Acalypha wilkesiana in Carrageenan induced paw
oedema in rats.
In this eddys hot plate method the flower extract increased the tolerance capacity of the animals ,the extract has the capacity
to inhibit strong and centrally mediated types of pain [13].
The abdominal constriction response induced by acetic acid is a sensitive procedure to establish peripherally acting
analgesics; the response is thought to be mediated by peritoneal mast cells [14], acid sensing ion channels [15] and the prostaglandin
pathways [16]. The significant anti nociceptive activity of Acalypha wilkesiana flower extract might be due to presence of analgesic
principles acting with prostaglandin pathways. However true analgesic activity can only be ensured by the combination of atleast two
methods as the acetic acid induced abdominal constriction can provide false positive results [17]. Denaturation of proteins is a well
documented cause of inflammation. The flower extract was effective in inhibiting heat induced albumin denaturation and maximum
percentage of inhibition was observed. The extract exhibited membrane stabilization effect by inhibiting hypo tonicity induced lysis of
erythrocyte membrane. The erythrocyte membrane is analogous to the lysosomal membrane and its stabilization implies that the
extract may as well stabilize lysosomal membrane.
In the anti inflammatory study the flower extract of the plant produced significant inhibition of paw inflammation induced by
carrageenan. histamine, serotonin[18] and prostaglandins play a major role in the development of carrageenan induced paw oedema
model in rats is known to be sensitive to cycloxygenase inhibitors and has been used to evaluate the effect of non steroidal anti
inflammatory agents which primarily inhibit the cycloxygenase involved in prostaglandin synthesis [19]. the time course of oedema
development in carrageenan induced paw oedema model in rats is generally represented by a biphasic curve [20].the first phase of
inflammation within a hour of a carrageenan injection and is partly due to the trauma of injection and also to the second phase of
inflammatory reaction which is measured at 3rd hr [21] .the presence of pge2 in the inflammatory exudates from the injected foot can be
demonstrated at 3hr and period thereafter. therefore it can be interfered that the inhibitory effect of ethanolic flower extract of
acalypha wilkesiana on carrageenan induced inflammation could be due to inhibition of the enzyme cycloxygenase leading to
inhibition of prostaglandin synthesis. significant inhibition of paw oedema in the early hours of study by acalypha wilkesiana could be
contributed to the inhibition of histamine [22] and /or serotonin.
CONCLUSION
This study has established the analgesic and anti inflammatory effect of flower extract of Acalypha wilkesiana in laboratory
animals and thus justifies the local uses of the plant for the treatment of these conditions in humans. Further studies will attempt to
look into the identification purification and characterization of specific phytochemical agents that are responsible for the observed
biological effects

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Competing Interests
The authors declare no conflict of interest.

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Authors Statements
The authors are thank full to the management and staff of Sri Sai Aditya Institute of Pharmaceutical Sciences and Research,
Surampalem, East Godavari District, Andhra Pradesh for their encouragement and providing necessary facilities to carry out the
research work successfully

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