Journal of Forensic Toxicology and Pharmacology

Altawil et al., J Forensic Toxicol Pharmacol 2015, 4:1
http://dx.doi.org/10.4172/2325-9841.1000133
Journal of Forensic
Toxicology and
Pharmacology
Research Article
A SCITECHNOL JOURNAL
Analgesic, Antipyretic and AntiInflammatory Activities of the
Egyptian Spitting Cobra, Naja
Nubiae Venom
Hanan JA Altawil1, Mohamed A Abdel-Rahman1, Mohamed S ElNaggar1, Zakaria A El-Khayat2 and Mohamed M Abdel-Daim3*
1Department of Zoology, Faculty of Science, Suez Canal University, Ismailia,
Egypt
2Department
of Clinical Biochemistry, National Research Centre, Dokki, Egypt
3Department
of Pharmacology, Faculty of Veterinary Medicine, Suez Canal
University, Ismailia, Egypt
*Corresponding
author: Mohamed M Abdel-Daim, Department of Pharmacology,
Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt ,
Tel: +20643207052; E-mail: [email protected]
Rec date: Feb 06, 2015 Acc date: Mar 11, 2015 Pub date: Mar 13, 2015
Abstract
Objectives: Although many venomous snakes represent a
potential human health threat, their venoms provide a rich
source of active components, many of which have been
recently identified, and used as potential candidates for
pharmacological therapeutic purposes. The current study was
designed to evaluate the analgesic, antipyretic and antiinflammatory activities of the Egyptian spitting cobra Naja
nubiae venom.
Methods: The venom of N. nubiae was intraperitoneally
injected at two dose levels (1/10 and 1/5 LD50). The peripheral
and central analgesic effects were examined using acetic acidinduced abdominal writhing in mice and tail immersion test in
rats, respectively. Brewer’s yeast-induced pyrexia in rats was
carried out to determine the antipyretic activity of the same
doses, whereas the anti-inflammatory activity was tested using
carrageenan-induced paw edema in mice.
Results: The results showed that N. nubiae venom produced a
significant analgesic activity in acetic acid-induced abdominal
constriction response in mice and thermal nociception in rat.
Moreover, the venom revealed a significant antipyretic effect on
yeast-induced pyrexia. In paw edema, venom exhibited a
significant activity with a maximum percentage of inhibition
reaching 60.1% on both doses after 5 hour treatment, which
was more powerful when compared with the standard drug;
diclofenac sodium (38.6%). Histologically, the venom induced a
moderate inflammatory cells infiltration in the dermis of paw.
Conclusion: These results suggest potential analgesic,
antipyretic, and anti-inflammatory activities of the Egyptian
spitting cobra crude venom.
Keywords: Naja nubiae; Snake; Venom; Analgesic; Antipyretic;
Anti-inflammatory; Pharmacology; Egypt
Introduction
Venomous snakes became the subject of intense studies for
understanding their venoms' biochemical composition, and the
mechanisms by which they cause harmful effects. In spite of their
toxicological effects, several isolated snake venom proteins and
peptides have a wide range of pharmaceutical activities [1]. Snake
venoms possess heterogeneous composition of proteins, peptides,
carbohydrates, lipid and amines, that act by different mechanisms to
cause paralysis, death and digestion of the prey, and to defend against
predators [2]. On the other hand, they possess antimicrobial activity
against gram-positive and gram-negative bacteria [3-4], antiviral
activity against several types of viruses, including Herpes simplex virus
[5], yellow fever and dengue [6], antiparasitic activity against
Leishmania [7] and Plasmodium species [8], antifungal activity [9] and
anticancer activities [10].
In addition, several snake venoms displayed analgesic properties in
experimental animal models of acute and chronic pain and humans as
well. Data from the beginning of the last century indicated that, certain
snake venoms, when administered in different formulations to human
beings, induce potent and long-lasting analgesic effects [11]. For
example, the long-chain -neurotoxin from Thailand's cobra venom
had anti-inflammatory and antnociceptive effects on adjuvant-induced
arthritis [12]. The Cobra is the most venomous snake in the world and
caused human deaths. The Egyptian Spitting cobra (genus Naja) has a
highly modified venom apparatus enabling it to eject a fine stream of
venom from their fang tips for several meters, that cause painful and
potentially blinding ocular envenoming [13].
Recently, proteomic analysis of spitting cobra venom revealed high
cytotoxin and cardio toxin protein family [14]. Crude N. nigricollis
venom screened for cytotoxicity against B16F10 melanoma and mouse
chondrosarcoma cell lines [15]. In addition, some peptides isolated
from its venom exhibit antimicrobial activity [16]. Although many
natural products have been used traditionally for their medicinal
purposes, there is still huge need for these products to solve many
emerging health problems [17-19]. The present study was designed to
evaluate the analgesic, antipyretic and anti-inflammatory effect of
crude Egyptian spitting cobra N. nubiae venom on experimental
animal models.
Materials and Methods
Venom collection and preparation
Naja nubiae was identified by department of Wild Life Management
and Zoo Medicine, Faculty of Veterinary Medicine, Suez Canal
University, Ismailia, Egypt, and the venom was collected from the
snakes by manual milking. Then, the venom were pooled, lyophilized
and stored at -20°C. The venom powder was dissolved in the
appropriate buffer and centrifuged prior to use.
Experimental animals
All animals used in the present study and experimental protocol
were approved by the Research Ethics Committee of Faculty of
Veterinary Medicine, Suez Canal University, and were carried out in
accordance with the Guide for the Care and Use of Laboratory
Animals (Approval No. 201503 ). Adult male albino mice (20-25 g)
and albino rats (100-150 g) were purchased from the breeding unit of
All articles published in Journal of Forensic Toxicology and Pharmacology are the property of SciTechnol and is
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Citation:
Altawil HJA, Abdel-Rahman MA, El- Naggar MS, El-Khayat ZA, Abdel-Daim MM (2015) Analgesic, Antipyretic and Anti-Inflammatory Activities of
the Egyptian Spitting Cobra, Naja Nubiae Venom. J Forensic Toxicol Pharmacol 4:1.
doi:http://dx.doi.org/10.4172/2325-9841.1000133
Theodor Bilharz Research Institute (Cairo, Egypt). Mice and rats were
left for 1 weak to adapt to laboratory conditions. They were kept in
plastic cages with wire mesh covers. The animals were kept under
standard environmental conditions of temperature and humidity and
fed with standard diet and water ad libitum.
Estimation of Median Lethal Dose (LD50)
The venom of N. nubiae with different known doses (D) was
injected intraperitoneally into 8 weighted mice, and then these animals
were observed to record the mortality for each. After injection, the
survival time (T; time between injection and death) of each animal for
24 hours was recorded. The regression line was plotted using the
values of D/T versus D, and the LD50 was calculated according to
Meier and Theakston [20].
Analgesic activities
The antinociceptive activities of N. nubiae venom were evaluated
using mice acetic acid-induced writhing test and rat tail immersion
test.
Acetic acid-induced writhing test
Healthy male mice weighing (20-25 g) were used and withdrawn
from food 2 hours before the start of experiment, and were divided
into four groups (6 mice each). The 1st group was intraperitoneally
injected with physiological saline (10 mg/kg), and considered as a
control. The 2nd group received 1/10 LD50 (0.042 mg/kg) of N. nubiae
venom. The 3rd group received 1/5 LD50 (0.084 mg/kg) of the venom,
and the 4th group received standard drug; aspirin (100 mg/kg ip).
Thirty minutes later, all groups were intraperitoneally administered
1% glacial acetic acid (10 ml/kg). The number of abdominal
constrictions was counted after 5 minutes of acetic acid administration
for the period of 15 minutes. As evidence of reduction of writhing
percent inhibition of writhing was calculated according to the
following formula (control mean-treated mean) /control mean ×100
[21].
Rats tail immersion test
Adult male albino rats weighing (100–140 g) were used, and divided
into four groups each of 6 animals. The 1st group received Saline (10
ml/kg). The 2nd and 3rd groups received N. nubiae venom at the dose
of 1/10 LD50 (0.147 mg/kg), 1/5 LD50 (0.294 mg/kg), respectively. The
4th group intraperitoneally given morphine (10 mg/kg). The animal
was kept in vertical position to hang the tail, which was up to 3cm into
55 ± 0.5°C water bath. The time in seconds to withdraw the tail out of
water was taken as the reaction time (Ta). The reading was taken after
0,1,2,3,4 and 5 hours of administration of the test drugs while Tb was
considered as the reaction time for the control group. Percentage of
analgesic activity =Ta – Tb/Tb × 100 [22].
Brewer's yeast-induced pyrexia in rats
Antipyretic activity of N. nubiae venom was evaluated by Brewer's
yeast induced pyrexia in rats as described by [23]. Twenty four male
albino rats were randomly divided into four equal groups, each of 6.
The 1st group received normal saline (10 ml/kg), and served as a
control. The 2nd and 3rd groups intraperitoneally injected with the
venom (1/10 LD50 and 1/5 LD50 and mg/kg, respectively) (0.147 and
0.294 mg/kg). The 4th group received the standard drug; metamizole
(5 mg/kg). The fever was induced by injection of dried yeast
Volume 4 • Issue 1 • 1000133
(Saccharomyces cerevisiae) (20% aqueous suspension in physiological
saline, 10 ml/kg body weight) at the nape of the neck. The initial body
temperature was measured rectally with a lubricated digital
thermometer, 17 hour after the yeast injection to determine the pyretic
response to yeast. Only rats that showed an increased temperature of
at least 0.5°C were selected for the experiment. Then, test agent and
standard drug were intraperitoneally administered. The temperature
was recorded at 1 hour intervals for 5 hours after drug administration.
Carrageenan-induced paw edema in mice
Anti-inflammatory activity of N. nubiae venom was evaluated using
carrageenan-induced mouse paw edema [24]. In this method,
approximately 50 µL of 1% carrageenan suspension (prepared one
hour before the experiment by dissolving 50 mg of carrageenan
powder in 5 ml of 0.9% physiological NaCl) was injected
subcutaneously into the plantar surface of the right hind paw. The
animals were randomly divided into five groups (6 mice each). The
2nd, 3rd, 4th and 5th groups were intraperitoneally injected with
saline (10 ml/kg), (0.084 and 0.042 mg/ kg of the venom) and
diclofenac sodium (1 mg/kg), respectively. Then, carrageenan was
administered, 1 hour later. The 1st group was used as a control, and
received 10 mg/kg saline. Paw thickness was measured before
carrageenan injection (zero time) and at 1 hour intervals for 5 hours
using a skin caliber.
The anti-inflammatory activity was calculated as percent inhibition
of carrageenan–induced paw edema using the following formula [25]:
Inhibition percent = (control mean-treated mean) /control mean
×100
At the end of the experiment, mice were sacrificed and specimens of
paw tissue were taken for histopathological examination. For each
group, four sections of the whole paw stained with hematoxylin and
eosin and evaluated using a light microscope.
Statistical Analysis
The obtained data were represented as mean ± standard errors of
mean (SEM) of 6 animals. The data were analyzed statistically using
analysis of variance (one-way ANOVA) followed by Dunkin test for
multiple comparisons. Statistical significance was considered at
P˂0.05. Statistical Package for Social Sciences (SPSS) for Windows
version 20 software was used throughout this analysis.
Results
Acute toxicity study
The approximate LD50 of N. nubiae venom was calculated to be
0.42 mg/kg body weight, and 1/5 and 1/10 LD50 (0.084 and 0.042 mg/
kg) have been used in the pharmacological properties of this venom.
Analgesic activities
Using the mouse writhing test, N. nubiae venom was significantly
(P<0.05) reduced writhing behavior in a dose dependent manner. The
inhibition percents were 60.60, 72.00, and 55.26 for the venom at 0.084
and 0.042 mg/ kg and aspirin (100 mg/kg), respectively (Table 1).
Regard to the rat tail immersion test, the analgesic effect of the
venom administrated at doses of 0.147 and 0.294 mg/kg caused a
• Page 2 of 6 •
Citation:
Altawil HJA, Abdel-Rahman MA, El- Naggar MS, El-Khayat ZA, Abdel-Daim MM (2015) Analgesic, Antipyretic and Anti-Inflammatory Activities of
the Egyptian Spitting Cobra, Naja Nubiae Venom. J Forensic Toxicol Pharmacol 4:1.
doi:http://dx.doi.org/10.4172/2325-9841.1000133
potent time increase in the tail flick response latency time as compared
to the control as shown in (Table 2).
Treatment
Number of Writhing
per 10 minute
% Inhibition (PIP)
Acetic acid control
36.83 ± 1.47
1/10 LD50 venom
14.50 ± 0.96*
60.60*
1/5 LD50 venom
10.33 ± 1.12*
72.00*
Aspirin (100 mg/kg)
16.50 ± 0.96*,#
55.26*,#
Mean ± SEM (6 animals / group). (*) Represents a significant
difference between Acetic acid control and treated groups using
Student Unpaired t-test (p<0.05). (#) Represents a significant among
all groups using one-way ANOVA (P ≤ 0.05).
The maximum effect of the venom (0.294 mg/kg) was observed at
1st hour; a percentage of inhibition reaching 149.50% while at the dose
of 0.147 mg/ kg it was 106.00%.
Table 1: Analgesic effect of Naja nubiae venom using acetic acidinduced abdominal writhing in mice (Note: Data are presented as
Response time after drug treatment (seconds)
Treatment
0 hour
1st hour
2nd hour
3rd hour
4th hour
5th hour
Normal control
1.83 ± 0.31
2.00 ± 0.26
2.50 ± 0.22
2.33 ± 0.33
2.00 ± 0.37
1.83 ± 0.17
1/10 LD50 venom
2.52 ± 0.19
4.12 ± 0.14*
3.73 ± 0.27*
4.68 ± 0.35*
3.58 ± 0.21*
2.74 ± 0.24*
1/5 LD50 venom
2.50 ± 0.22
4.99 ± 0.81*
4.71 ± 0.41*
4.81 ± 0.27*
3.55 ± 0.33*
2.88 ± 0.28*
2.33 ± 0.21
6.17 ± 0.54
5.17 ± 0.4
4.87 ± 0.1
4.41 ± 0.46
3.47 ± 0.29
Morphine
mg/kg)
(3
Table 2: Analgesic effect of Naja nubiae venom using tail immersion test in rats (Note: Data are presented as Mean ± SEM (6 animals / group).
(*) Represents a significant difference between normal control and treated groups using Student Unpaired t-test (p<0.05). (#) Represents a
significant difference between all groups at time intervals using one-way ANOVA (P ≤ 0.05).
Antipyretic effect of N. nubiae venom
The experimental rats showed a mean rectal temperature higher
than 38°C in18 hours after yeast injection. Treatment with N. nubiae
venom (0.147 and 0.294 mg/kg) significantly (P<0.05) reduced the rat
elevated rectal temperature.
The antipyretic effect started from the first hour until 5 hours, after
administration of venom as shown in (Table 3). The difference
between two doses of N. nubiae venom was non-significant.
Rats Body Temperature (°C)
Treatment
0hr
1st hr
2nd hr
3rd hr
4th hr
5th hr
Yeast control
38.80 ± 0.22
38.90 ± 0.17
38.80 ± 0.19
38.70 ± 0.19
38.70 ± 0.17
38.60 ± 0.13
1/10 LD50 venom
38.90 ± 0.11
38.00 ± 0.10*
38.20 ± 0.16*
38.30 ± 0.21
38.50 ± 0.19
38.60 ± 0.20
1/5 LD50 venom
38.60 ± 0.13
37.90 ± 0.15*
37.70 ± 0.13*
37.90 ± 0.10*
38.10 ± 0.10*
38.20 ± 0.10*
Metamizol (5 mg/kg)
38.80 ± 0.24
38.10 ± 0.25
37.80 ± 0.26
37.50 ± 0.31*
37.80 ± 0.25*
38.10 ± 0.24
Table 3: Antipyretic effect of Naja nubiae venom using Brewer’s yeast-induced pyrexia in rats. (Note: Data are presented as Mean ± SEM (6
animals /group). (*) Represents a significant difference between yeast control and treated groups using Student Unpaired t-test (p<0.05). (#)
Represents a significant difference between all groups at time intervals using one-way ANOVA (P ≤ 0.05).
Anti-inflammatory effect of N. nubiae
In the carrageenan-induced edema test, the paw thicknesses and
percentages of inhibition by both venom doses (0.084 and 0.042 mg/
kg), were shown in (Table 4).
The venom dose of 0.042 mg/kg showed a significant inhibition of
paw edema starting from the first hour up to the 5th hour, while the
dose of 0.084 mg/kg showed a significant inhibition of paw edema
starting from the 2nd hour up to the 5th hour.
Volume 4 • Issue 1 • 1000133
The venom reduced paw edema at a maximum percentage of
inhibition 60.15% obtained 5th hour after carrageenan injection
whereas diclofenac sodium showed a significant inhibition of paw
edema of about 36.23% at 5th hour.
Effect of venom in histopathology of foot paw
The histopathological changes in foot paw tissue of carrageenaninduced paw oedema showed thickness in epidermis, infiltration of the
• Page 3 of 6 •
Citation:
Altawil HJA, Abdel-Rahman MA, El- Naggar MS, El-Khayat ZA, Abdel-Daim MM (2015) Analgesic, Antipyretic and Anti-Inflammatory Activities of
the Egyptian Spitting Cobra, Naja Nubiae Venom. J Forensic Toxicol Pharmacol 4:1.
doi:http://dx.doi.org/10.4172/2325-9841.1000133
dermis with inflammatory cells like neutrophils, macrophages and
some lymphocytes and some areas showed loosely arranged
connective tissue.
On the other hand, mice treated with the venom at 0.084 or 0.042
mg/kg showed a reduction in the epidermis thickness.
Paw thickness (cm)
Treatment
0 hr
1st hr
2nd hr
3rd hr
4th hr
5th hr
Normal control
0.202 ± 0.002
0.2 ± 0.000
0.198 ± 0.002
0.2 ± 0.000
0.202 ± 0.002
0.202 ± 0.002
Carrageenan
0.21 ± 0.009
0.31 ± 0.009
0.36 ± 0.009
0.34 ± 0.009
0.33 ± 0.011
0.34 ± 0.009
1/10 LD50 venom
0.200 ± 0.000
0.283 ± 0.011 *
0.283 ± 0.011 *
0.258 ± 0.008 *
0.258 ± 0.008 *
0.250 ± 0.013 *
1/5 LD50 venom
0.200 ± 0.000
0.308 ± 0.0 08
*
0.292 ± 0.008 *
0.275 ± 0.011 *
0.275 ± 0.011 *
0.267 ± 0.011 *
Diclofen (20 mg/kg)
0.200 ± 0.000
0.266 ± 0.011*
0.300 ± 0.013*,#
0.292 ± 0.008*,#
0.292 ± 0.008*,#
0.283 ± 0.011*,#
Table 4: Anti-inflammatory effect of Naja nubiae venom using carrageenan-induced paw oedema in mice. (Note: Data are presented as Mean ±
SEM (6 animals / group). (*) Represents a significant difference between carrageenan control and treated groups using Student Unpaired t-test
(p<0.05). (#) Represents a significant difference between all groups at time intervals using one-way ANOVA (P ≤ 0.05).
Moderate infiltration with inflammatory cells like neutrophils,
macrophages and some lymphocytes compared with the carrageenan
control group, all these observations shown in (Figure 1).
Figure 1: The histopathological changes in mice foot paw tissue
(Note: The histopathological changes in mice foot paw tissue (A)
Normal control mice foot paw tissue, (B) Carrageenan–induced
mice paw inflammation control, showed wide epidermis and
infiltration of the dermis with inflammatory cells like neutrophils,
macrophages and some lymphocytes. (C,D) Mice paw treated with
1/10, 1/5 LD50 (0.084 and 0.042 mg/ kg) N. nubiae venom showed
moderate infiltration with inflammatory cells like neutrophils,
macrophages and some lymphocytes. (E) Mouse treated with
diclofenac sodium (100 mg/kg) showed minimal infiltration with
some neutrophils and lymphocytes.
Discussion
The venoms of Elapid snakes, genus Naja, contain numerous
polypeptide components, the majority of which being toxins
(neurotoxins and cardiotoxins) responsible for the lethality of the bite.
In addition, the venom includes many bioactive molecules with
important pharmacological activities [26]. The present study was
carried out to evaluate antinociceptive, antipyretic and antiinflammatory activities of the crude Egyptian cobra (N. nubiae) venom
on the experimental animal models.
Volume 4 • Issue 1 • 1000133
Our study examined the analgesic effect of the N. nubiae venomtreated animals at the doses of 1/5 and 1/10 LD50 in models of
peripheral and central pain; writhing and tail immersion test
respectively. Intraperitoneal injection of acetic acid produces pain via
liberating endogenous substances and other pain mediators like
arachidonic acid via cyclooxygenase, and prostaglandin pathway [27]
or irritation of visceral surfaces, which lead to the release of histamine,
bradykinin, prostaglandins, and serotonin [28]. The venom could
reduce the writhing behaviors and increase tail withdrawal latency at
both tested doses through its peripheral and central effects
respectively, and its analgesic effect could be related to the inhibitory
action on the release of histamine, bradykinin, prostaglandins, and
serotonin. On the other hand, acid-sensing ion channels (ASICs) H+gated Na+ channels are generally considered principal players in the
pain pathway. Some researcher discovered two closely related 57
amino acid peptides in the venom of the deadly black Mamba snake
that produced potent and reversible blockade of ASIC1a. These
natural antagonists were effective analgesic, and that they acted on
several ASIC isoforms found in both the PNS and CNS [29]. These ion
channels might play a role in analgesic action of the venom.
Subcutaneous injection of yeast in rats induces pyrexia by
stimulation of the hypothalamic area that controls body temperature,
via prostaglandins synthesized within the central nervous system
(CNS), which results in increased heat production and decreased heat
loss. The inhibition of prostaglandin synthesis can be achieved by
inhibiting the cyclooxygenase enzyme production [27]. In the present
study, the venom at both tested doses and metamizole return the
elevated body temperature to its normal level, and this effect might be
due to its inhibition in central prostaglandins' synthesis [24].
The presence of edema is one of the prime signs of inflammation. It
has been documented that carrageenan-induced mice paw edema is a
suitable in vivo model to predict the value of anti-inflammatory
agents, which act by inhibiting the acute inflammatory mediators, and
this method has frequently been used to assess the anti-edematous
effect of natural products [30]. Inflammation induced by carrageenan
was observed to have biphasic the initial phase is due to release of
histamine, serotonin and kinin in the first hour after the
administration of carrageenan, and late phase (2–3 hours) has been
• Page 4 of 6 •
Citation:
Altawil HJA, Abdel-Rahman MA, El- Naggar MS, El-Khayat ZA, Abdel-Daim MM (2015) Analgesic, Antipyretic and Anti-Inflammatory Activities of
the Egyptian Spitting Cobra, Naja Nubiae Venom. J Forensic Toxicol Pharmacol 4:1.
doi:http://dx.doi.org/10.4172/2325-9841.1000133
shown to be a result of overproduction of prostaglandins, bradykinin
and lysosome like substance [31] after 3 hours.
The result of pre-treatment venom demonstrated that the venom
(at dose of 0.042 mg/ kg) and diclofenac sodium begin their effects at
the early phase (1 hour) of inflammation, the first phase begins
immediately after the injection of carrageenan, and diminishes in 2
hours, which has been reported because of release of histamine and
serotonin primarily. Based on this an assumption can be made that
may be showing its effect through inhibition of histamine and
serotonin release. The higher dose of the venom (0.084 mg/kg)
induced a significant inhibition starting from the 3rd hour of
inflammation, while the second phase begins after 2nd hour, and
remains up to 5 hours, which has shown its effect through inhibition
of the release of prostaglandin-like substances. The two venom doses
inhibited mice paw volume by 60% at 5th hour of carrageenan
injection. The results were higher than that of diclofenac sodium,
which reduced the paw volume by 36%. As the carrageenan-induced
inflammation is a significant predictive test for anti-inflammatory
agents acting by inhibiting the mediators individually or in
combination. Which agreed with previous studies, the neurotoxin
from Thailand's cobra venom, had anti-inflammatory and
antinociceptive effects on adjuvant arthritis [12]. The histopathology
of the mice foot paw confirm our previous results as both tested doses
reduced inflammatory cells' infiltration, including neutrophils,
macrophages and some lymphocytes compared to the carrageenaninduced- non treated control group, which confirmed of inhibition of
inflammation in tissue with two doses venom.
Finally, many compounds with anti-inflammatory activity could
also have analgesic activity and antipyretic activity [24], which is also
in agreement with our findings on the analgesic, antipyretic and antiinflammatory activity of venom.
Conclusion
The present study showed potential analgesic, antipyretic and antiinflammatory effect of both venom doses in various animal models.
Further studies are required to isolate the venom active constituents,
and to examine the molecular and more specific mechanism of action.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Acknowledgement
This study received no fund from any funding organization.
15.
Conflict of Interest
All authors confirm that, there is no conflict of interest regard to
this study.
16.
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