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Studies on Bee Venom and Its Medical Uses

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Studies on Bee Venom and Its Medical Uses

Abstract

Use of honey and other bee products in human treatments traced back thousands of years and healing properties are included in many religious texts including the Veda, Bible and Quran. Apitherapy is the use of honey bee products for medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom therapy is the use of live bee stings (or injectable venom) to treat various diseases such as arthritis, rheumatoid arthritis, multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow to name a few. It refers to any use of venom to assist the body in healing itself. Bee venom contains at least 18 pharmacologically active components including various enzymes, peptides and amines. Sulfur is believed to be the main element in inducing the release of cortisol from the adrenal glands and in protecting the body from infections. Contact with bee venom produces a complex cascade of reactions in the human body. The bee venom is safe for human treatments, the median lethal dose (LD50) for an adult human is 2.8 mg of venom per kg of body weight, i.e. a person weighing 60 kg has a 50% chance of surviving injections totaling 168 mg of bee venom. Assuming each bee injects all its venom and no stings are quickly removed at a maximum of 0.3 mg venom per sting, 560 stings could well be lethal for such a person. For a child weighing 10 kg, as little as 93.33 stings could be fatal. However, most human deaths result from one or few bee stings due to allergic reactions, heart failure or suffocation from swelling around the neck or the mouth. As compare with other human diseases, accidents and other unusual cases, the bee venom is very safe for human treatments.
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 1
ISSN 2278-7763
Copyright © 2012 SciResPub.
Studies on Bee Venom and Its Medical Uses
Mahmoud Abdu Al-Samie Mohamed Ali
Department of Plant Protection, Faculty of Agriculture, Ain Shams University, Cairo, Egypt.
(Present Address: Honey bee Expert, Arab Organization for Agricultural Development, League of Arab States, Ministry of Agriculture,
Riyadh, K.S.A.).
E-mail: honeybee1433@hotmail.com.
ABSTRACT
Use of honey and other bee products in human treatments traced back thousands of years and healing properties are
included in many religious texts including the Veda, Bible and Quran. Apitherapy is the use of honey bee products for
medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom
therapy is the use of live bee stings (or injectable venom) to treat various diseases such as arthritis, rheumatoid arthritis,
multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow to name a few. It refers to any use of venom to
assist the body in healing itself. Bee venom contains at least 18 pharmacologically active components including various
enzymes, peptides and amines. Sulfur is believed to be the main element in inducing the release of cortisol from the
adrenal glands and in protecting the body from infections. Contact with bee venom produces a complex cascade of
reactions in the human body. The bee venom is safe for human treatments, the median lethal dose (LD50) for an adult
human is 2.8 mg of venom per kg of body weight, i.e. a person weighing 60 kg has a 50% chance of surviving injections
totaling 168 mg of bee venom. Assuming each bee injects all its venom and no stings are quickly removed at a maximum of
0.3 mg venom per sting, 560 stings could well be lethal for such a person. For a child weighing 10 kg, as little as 93.33 stings
could be fatal. However, most human deaths result from one or few bee stings due to allergic reactions, heart failure or
suffocation from swelling around the neck or the mouth. As compare with other human diseases, accidents and other
unusual cases, the bee venom is very safe for human treatments.
Keywords: honey bees, apitherapy, bee venom, bee sting, chemical composition, physical properties, medical
uses.
1 INTRODUCTION
The exact origins of apitherapy are difficult to pinpoint
and can be traced back to ancient Egypt, Greece and has
been practiced in China for 3-5000 years (Rose, 1994). Use
of honey and other bee products can be also traced back
thousands of years and healing properties are included in
many religious texts including the Veda, Bible and Quran
[5], [6]. Now it is being practical all over the world. In the
USA the history of apitherapy goes back about 100 years,
it was practiced by several prominent doctors including
Dr. Bodog Beck, who started treating people in his New
York City office in the late 1920's. Dr. Beck's book "Bee
Venom Therapy" has been classic for 60 years. The last
surviving student of Dr. Beck is Middlebury, Vermont
beekeeper named Charles Marz, who was known by the
many as the "King of bee venom therapy". He had been
practicing apithirapy for over 60 years with remarkable
results, and most of his experience had been with treating
arthritis, but his success was with multiple sclerosis (MS)
[7].
Among the many species of insects, only very few
have the capability of defending themselves with a sting
and venom injection during stinging. All insects that can
sting are members of the order Hymenoptera, which
includes ants, wasps and bees. Since the sting is believed
to have evolved from the egg-laying apparatus of the
ancestral, hymenopteran species, only females can sting.
The sting is always at or near the abdominal end, rather
than the head. Therefore the pain inflicted by a honeybee,
defending its colony, is not caused by a bite, as is
frequently said, but by a sting [8]. The larger drone bees,
the males, do not have stingers. The female worker
bees are the only ones that can sting, and their stinger is a
modified ovipositor. The queen bee has a smooth stinger
and can, if need be, sting skin-bearing creatures multiple
times, but the queen does not leave the hive under
normal conditions. Her sting is not for defense of the
hive; she only uses it for dispatching rival queens, ideally
before they can finish pupating [8].
Bee venom (BV) therapy which utilizes the application
of bee venom to treat various diseases has been used
since ancient times in traditional medicine [1], [2], [3], [4],
[92], [101], [133]. Honey bee venom as a well-known
pharmacologically active product of the hive. It is
synthesized by the venom glands associated with the
sting apparatus of worker and queens, stored in the
venom reservoir, and injected through the sting
apparatus during the stinging process [9], Its production
increases during the first two weeks of the adult worker's
life and reaches a maximum when the worker bee
becomes involved in hive defense and foraging. It
diminishes as the bee gets older [8]. A mature defender or
forager contains about 100-150 µg of venom, and it inject
0.15 0.30 mg of venom via its stinger [10],
a honeybee can inject 0.1 mg of venom via its stinger. The
queen bee's production of venom is highest on
emergence, probably because it must be prepared for
immediate battles with other queens [8]; the young queen
contains about 700 µg [11].
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 2
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Copyright © 2012 SciResPub.
However, BV administration was reported to stimulate
the function of immune system [12] and to affect the
release of cortisol production which is known as natural
anti-inflammatory agent [13]. Melittin which is the major
component of BV was found to suppress inflammation by
inhibiting phospholipase (PLA) enzymatic activity [14].
This enzyme was abundantly released in severe
inflammatory disorders and actively found to cause
tissue and organ degradation which will lead to the loss
of their functions [15]. Furthermore, melittin was also
found to block the production of neutrophil superoxide
[16].
A large number of studies have been carried out on the
composition of honeybee venom. Much of the basic
identification of compounds, their isolation and the study
of their pharmacological effects of bee venom was done
in the 1950's and 1960's. There are some comprehensive
summaries in [17] which cover the morphology of the
venom apparatus, the collection of venom, the
pharmacological effects of bee venom and allergies to the
Hymenoptera venom of bees, wasps and ants. [11]
presents a comprehensive account of allergies to
honeybee and other Hymenoptera venoms. [18], [19],
[20], [21] give a very good overview of its composition,
effects, harvesting and use.
2 PHYSICAL CHARACTERISTICES OF
VENOM
Honeybee venom is a transparent liquid dries up
easily even at room temperature, odourless, ornamental
pungent smell, a bitter taste, hydrolytic blend of proteins
with basic pH (4.5 to 5.5) that is used by bees for defense
[8], [9]. When coming into contact with mucous
membranes or eyes, it causes considerable burning and
irritation. Bee venom is soluble in water and insoluble in
alcohol and ammonium sulfate. When it comes in contact
with air it forms grayish-white crystals. Dried venom
takes on a light yellow colour and some commercial
preparations are brown, thought to be due to oxidation of
some of the venom proteins. Bee venom contains a
number of very volatile compounds which are easily lost
during collection, it is considered a rich source of
enzymes, peptides and biogenic amines, it is specific
weight 1.1331 [22], [8].
3 THE COMPOSITION OF BEE VENOM
The venoms of most stinging insects including honey
bees consisted of enzymes, protein, peptides, and a verity
of smaller molecules (Table 1). The pharmacological and
biochemical activities of the various stinging insect
venoms remarkably convergent. Most venoms induce
immediate pain, contain phosphlipases, hyaluronidase,
and other enzymatic activities, and are capable of
destroying red blood cells [22]. Most hymenopterous
venoms also contain low molecular weight peptides that
are highly basic and have isoelectric points ranging from
pH 9-12 [23], [24], [25], [26], [27], [28], [29], [30], [31].
TABLE 1
Biochemical composition of venom of insects that
frequently sting humans. a (as cited by [42]).
Class of
molecul
es
Hone
y bees
Yello
w
jacket
Pap
er
wa
sps
Ho
rne
ts
Fire
ant
s
Harve
ster
ants
Bul
l
ant
s
Bumb
le
bees
Enzyme
s
Phospholip
ase A2
10-
12%
0
0
0
+
+b
+b
+b
A1
0
+
+
+
B
1%
+
+
+
+
+
0
+
Hyaluronid
ase
1-2%
+
+
+
+/-
+
+
+
Acid
Phosphates
1%
0
0
+
+
+
Alkaline
Phosphates
+
0
0
+
Lipase
0
+
+
+
Esterase
+
+
+
+
Protease
0
0
0
0?
0
0
Peptides
Melittin
40-
50%
0
0
0
0
0
Apamine
3%
(0)
(0)
(0)
(MCD)-
Peptide
2%
(0)
(0)
(0)
Secapin
5%
Tertiapin
1%
Bombolitin
s
0
0
Kinins
0
+
+
+
+
Mastopara
ns
0
+
+
+
Chemotacti
c
Peptides
0
+
+
Antigen 5
0
+
+
+
Vespid
neurotoxins
0
+
+
Barbatolysi
n
0
0
0
0
+
Small
molecul
es
Histamine
0.7-
1.6%
+
+
+
+
+
Dopamine
0.1-1%
+
+
+
Norepinep
hrine
0.1-
0.2%
+
0
+
Acetylcholi
ne
0
0
0
+
0
+
Putescine
0
+
Serotonin
0
+
+
+
0
0
Tyramine
0
+
+
+
Leukotrien
es
0.003
%
+
+
Alkaloids
0
0
0
0
95
%
0
a Data from: [17], [110], [111], [22],[112], [113],[37], [38],
[115], [36], [116]; b Specificity of A1, or A2 unknown.
In contrast to pharmacological similarities of insect
venoms, their biochemical structure differ remarkably
among the varies taxa. The phospholipases derived from
honey bees, yellow jackets, and fire ants have very
different molecular weights: 16,000 for bees [32], 30,000 to
37,000 for yellow jackets [33], [34], [35], [36], and 28.000 in
the form of tow roughly equal subunits for fire ants [37].
their specific activities are also strikingly different as
indicated by the assignments of A2, A1, or B activity
(Table 1). This activities refer to the side of hydrolysis of
the phospholipids and how many sides can be
hydrolyzed by the enzyme (designations for the "activity
of the ants is not known and can be either A1 or A2). The
amino acid compositions and sequences of the
phospholipases are also different as determined by direct
analysis [32], [38], [37] and lack of cross-reactivity by
antibodies [39], [40], [41]. The venom of honey bees,
yellow jacket, paper wasps, true hornets, and harvester
ants all contain small, highly basic pain-inducing
peptides. These algogenic peptides exhibit almost no
structure similarities among the venoms of the different
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insects families. The honey bee peptide, melittin, contains
26 amino acids, seven which form a very hydrophilic end
of the molecule and 19 which form a highly hydrophobic
end.
As cited by [42], the allergens in bee, wasp, and ant
venoms are all proteins (Table 2). These proteins are not
generally believed to cause immediate sting pain
(melittin, a minor allergen is an exception [43]), but cause,
or enhance, toxicity, and all are capable of inducing
hypersensitive reactions in some individuals. An evident
feature in Table (2) as that all of these allergens except
hyaluronidase and possible acid phosphatase are
restricted to the members of only one specific family of
stinging insects. Modern biochemical analysis has been
employed to identify the components in BV. As a result,
there are at least 18 pharmacologically active components
have been described, including various enzymes, a
variety of peptides and amines (i.e melittin, apamin,
adolapin and mast-cell-degranulating (MCD) peptide),
enzymes (i.e., phospholipase [PL] A2, hyaluronidase) and
biologically active amines (i.e., histamine and
epinephrine). Besides that, BV also contains nonpeptide
components such as lipids, carbohydrates and free amino
acids. These BV components were reported to have a
wide variety of pharmaceutical properties [44]. The major
components of bee venom as summarized from [19], [45],
as cited by [8] are lists in (Table 3). The bee venom
contains 88% water. The glucose, fructose and
phospholipid contents of venom are similar to those in
bee's blood [18]. [46] stated that the main component
of bee venom responsible for pain in vertebrates is the
toxin melittin; histamine and other biogenic amines may
also contribute to pain and itching. They also found the
melittin comprising 52% of venom peptides. The melittin
is a strong anti-inflammatory agent and induces the
production of cortisol in the body. Apamin increases
cortisol production in the adrenal gland. Apamin is a
mild neurotoxin. Adolapin, comprising 2-5% of the
peptides, acts as an anti-inflammatory
and analgesic because it blocks cyclooxygenase.
Phospholipase A2 comprises 10-12% of peptides and it is
the most destructive component of apitoxin. It is
an enzyme which degrades the phospholipids which
cellular membranes are made of. It also causes
decreased blood pressure and inhibits blood coagulation.
Phospholipase A2 activates arachidonic acid which is
metabolized in the cyclooxygenase-cycle to
form prostaglandins. Prostaglandins regulate the body's
inflammatory response. The toxin from wasps contains
phospholipase A1. Hyaluronidase comprising 1-3% of
peptides dilates the capillaries causing the spread of
inflammation. Histamine comprising 0.5-2% and is
involved in the allergic response.
Dopamine and noradrenaline which comprise 1-2%
increase pulse rate. Protease-inhibitors comprise 2% and
act as anti-inflammatory agents and stop bleeding.
Venom from other Apis species is similar, but even the
venoms from the various races within each species are
slightly different from each other. The toxicity of Apis
cerana venom has been reported to be twice as high as
that of A. mellifera [47].
TABLE 2
Known allergens in insect venomsa, as cited by [42].
Allergen
Percent of Venom
Allergenic
importanc
e
Mol.Wt
Honey
bee
Vespid
wasps
Fire
ants
Phospholipase A2
15,800
10-
12%
-
-
major
Phospholipase
A1B
31-
37,000
-
10-25
-
major
Phospholipase
A1B
28,200
-
-
10-12c
major
Hyaluronidase
40-
46,000b
1-2
1.5-5
+/-
Maj/mode
r
Acid Phosphates
98,000d
1
-
1
Mod/mod
Antigen 5
22-
25,000
-
15-40
-
major
Antigen C
102,000
1
-
-
moderate
V mac 1
97,000
-
1
-
moderate
V mac 3
39,000
-
1
-
major
Solenopsis I
35,000
-
-
5-1c
major
Solenopsis III
26,000
-
-
3c
major
Solenopsis IV
14,000
-
-
1-1.5c
major
Melittin
2,800
40-60
-
-
major
a Data from: [117], [37], [33], [118], [119], [37], [120], [121],
[26], [40], [122], [38], [36]; b 40,000 for honey bee, 46,000
for yellow jacket ; c percent of venom protein; d for honey
bee.
TABLE 3
Composition of venom from honeybee worker, as cited
by [8].
Class of
molecules
Component
% of dry
venoma
% of dry
venomb
Enzymes
Phospholipase A2
10-12
10-12
Hyaluronidase
1-3
1.5-2.0
Acid
Phosphomonoesterase
1.0
Lysophospholipase
1.0
-glucosidase
0.6
Other
proteins and
peptides
Melittin
50
40 50
Apamine
1-3
3
Mast Cell Degranulating
Peptide (MCD)
1-2
2
Secapin
0.5-2.0
0.5
Procamine
1-2
1.4
Adolapin
1.0
Protease inhibitor
0.8
Tertiapinc
0.1
0.1
Small peptides (with less
than 5 amino acids)
13-15
Physiologicall
y active
amines
Histamine
0.5-2.0
0.6 -1.6
Dopamine
0.2 1.0
0.13 -1.0
Noradrenaline
0.1 0.5
0.1 0.7
Amino Acids
-aminobutyric acid
0.5
0.4
-amino acids
1
Sugars
Glucose & fructose
2
Phospholipids
5
Volatile
compounds
4 - 8
a [19], b [45], c This peptide may not be present in all
venom samples.
4 HONEY BEE VENOM COLLECTION AND
ADULT WORKER BEE COLLECTION
4.1 Venom Collection
Early collection methods of bee venom were required
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Copyright © 2012 SciResPub.
surgical removal of the venom gland or squeezing each
individual bee until a droplet could be collected from the
tip of the sting [8], [9]. Since the early 1960's, extraction by
the electro-shock method has been continuously
improved and is now standard procedure [48], [49], [50].
Different extraction or collection methods result in
different compositions of the final products venom
collected under water to avoid evaporation of very
volatile compounds seems to yield the most potent
venom [51]. Venom collected from surgically removed
venom sacs showed different protein contents from that
collected with the electroshock method [52]. [53] used a
cooling system with the standard electro-shock collecting
apparatus in order to preserve more of the volatile
compounds. This technology had followed various
electrical methods involving collecting venom from
individual or a limited numbers of bees [54], [132], [55]
and, for the first time, allowed the collection of a gram of
venom from about 20 colonies in a period of an hour or
two [9]. Although similar electrical methods work to an
extent with other stinging insects [56], [57], this method
appears to be viable method mainly for honey bees
[9].The standard electro-shock method cannot be
recommended for venom collection from Africanized
honeybees or the more defensive races [8]. Colony
arousal can become so overwhelming that bees start
killing each other and alert other colonies or attack the
beekeeper and bystanders. The mass reaction of
Africanized honeybees may also result in contamination
of the collected venom. Nevertheless, venom is collected
by this method in Brazil and Argentina, with only minor
modifications. Even European colonies remain disturbed
for up to a week after collection and it is said by [58] that
colonies from which venom has been collected every
three days produce 14% less honey, meanwhile, [50]
found no such evidence for reduced productivity,
however. [59] found that when using electro-shock
treatment, the most efficient collection cycle was three 15-
minute stimulations at intervals of three days, repeated
after 2 - 3 weeks. As cited by [8] an Argentinean
beekeeper found that by modifying the electric stimulus,
his collection efficiency greatly increased and the bees
remained disturbed for less time.
As cited by [18] the various trap designs stimulate bees
by applying a mild electric shock through wires above the
collecting tray. The most widely-used designs are
modifications of the one first presented by [48]. A review
by [60] discusses further developments. The trays are
placed either between the bottom board and brood
chamber at the hive entrance or in a special box between
supers and the hive cover, [132].
As cited by [8] it is unlikely that a bee will eject all the
contents of its venom sac, even after repeated stinging.
Therefore, typically, only 0.5 to 1.0 jil (0.2 j£l - [8] of
venom can be collected per bee, with an average of ten
stings per bee [55]. This results in less than 0.1 ijg (0.11 jig
[18] of dry venom per bee. Consequently, at least 1
million stings are required to make one gram of dry bee
venom. [19] report that 1 g of venom can be collected
from twenty hives over a two hour period. Exact
production figure are unavailable, the main venom
producer in the USA had produced about 3000 grams of
venom over 30 years [60].
4.2 Adult worker bee collection
Instead of collecting bee venom, adult bees may be
used to sting the patient directly. This is the way to apply
the venom in its freshest, most complete and cheapest
form [8]. To collect the bees, a small hole is made in the
brood chamber, super or inner cover. To avoid colony
disturbance, the hole is opened and a collecting jar placed
over it until a sufficient number of bees have come out.
Small groups (10-100) of workers can be maintained at
home for up to 2 weeks. They should be kept in the dark,
in a small box (with one side made of fly-screen) [7], [8]
or in a plastic or glass jar and with access to sugar syrup
or bee honey (crystallized honey is best) every 3-5 days
and pollen paste, and the bees also need water [7], the
box or the jar should supply with a piece of wax or some
wood sticks for bees to hang on. Care needs to be taken to
keep ants away. Alternatively, bees can be collected from
frames or from the hive entrance immediately by
scraping the bees into the jar or the box or by a suction
device or by the hand if the number of bees needed is
small.
5 THE ALLERGIC FOR HONEY BEE VENOM
A bee sting is strictly a sting from a bee (honey
bee, bumblebee, sweat bee, etc.). In the vernacular it can
mean a sting of a bee, wasp, hornet, or yellow jacket. The
stings of most of these species can be quite painful, and
are therefore an object of dread for many people [42]. The
bee stings differ from insect bites (horse-fly and ants), and
the venom or toxin of stinging insects is quite different.
Therefore, the body's reaction to a bee sting may differ
significantly from one species to another. The most
aggressive stinging insects are wasps (Family: Vespidae;
Order: Hymenoptera) including bald-faced hornets and
other yellow jackets but not hornets in general (e.g., the
European hornet is gentle) [42]. All of these insects
aggressively defend their nests. In people who
are allergic to bee stings, a sting may trigger a
dangerous anaphylactic reaction that is potentially
deadly.
5.1 Allergic Reactions to Insect Stings
As cited by [42] allergy is a general term that descriers
a verity of human symptoms and reactions to diversity of
materials including pollen, animal dander, foods, drugs,
dust mites (house dust), stinging insects and others.
Stinging insect allergy refers to sting-induce systemic
reactions of the body that occur at body locations distant
from the sting site. Allergic reactions do not include
immediate pain caused by the sting itself or to the
burning, redness, itching and swelling that might occur
around the sting site. Such reactions including very large
local swelling are referred to as "local reactions" [8]. [61]
stated that most stings cause localized swelling, redness,
and acute pain that may throb or burn. This is reaction to
the insects venom. Whoever, some people are highly
allergic to insect venom, and if they are stung, a very
severe reaction can occur. People who are highly allergic
to insect stings can experience anaphylactic shock, which
can lead to unconsciousness and, in extreme
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 5
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circumstances, death. Anaphylactic shock can cause
symptoms such as bluish skin, coughing, difficulty
breathing, dizziness, hives, nausea, severely swollen eyes,
lips or tongue, stomach cramps, and wheezing.
As cited by [8] although, bee venom is safe for human
treatment; it should only be used under the supervision
of a qualified health care professional. Most experts
recommend having an emergency sting kit available in
case of allergic reaction. This kit should include a syringe
and a dose of epinephrine and antihistamine tablets. The
kit can get by prescription from the doctor, be sure you
read the directions on the package before you get your
test sting. It is also advisable that a test sting be
performed before undergoing a treatment [7]. Those who
are sensitive to the test sting can be de-sensitized to bee
venom in order to undergo apitherapy. It is estimated
that 1% of the population is allergic to bee stings. Only a
small percentage of those allergic to a honeybee sting will
suffer anaphylactic shock [7]. A severe reaction just after
a few stings is rare, but the danger grows with the
number of stings. A person who is having a severe
reaction to a bee sting may develop hives on the skin and
swelling around the eyes, lips, throat, and tongue. The
person may vomit, slur words, show signs of mental
confusion and even struggle to breathe. This is usually
followed by the loss of consciousness. If any of these
signs are present, immediately consult with an
emergency medical professional.
In theory any stinging insect species can cause allergic
reaction in humans. This because an insect sting
introduces venom-which essentially is a blend of foreign
proteins- into the body where it contacts the immune
system and can induce production of allergy- causing
antibodies [42]. An allergic reaction typically occurs after
the second or subsequent stinging event by the same or a
closely related species. The first sting, (or stings), induces
the production of the allergy causing antibody,
immunoglobulin E (IgE), by the body resulting in the
sensitization of the individual to the venom. Later when
the now hipper sensitive individual is stung again, the
venom causes an IgE-mediate allergic reaction.
Normal and allergic reaction to stings can vary
enormously from individual to individual (Table 4, as
cited by [42]. Normal reactions are those that virtually
everybody experiences and are characterized mainly by
pain and burning that typically are in tense for a few
minutes and then decrees over time. After the intense
pain decreases a redness and swelling are oven observed
and this can last several hours to a day or more. Like
normal (non-allergic) reactions, large local reaction is
nothing to be feared. Though they are thought to be
immunologically based reactions [62], [63], [64], [65], [66],
they rarely progress to systemic reaction [63], [65], [66],
67], [68]. Moreover, the frequency of individual who
experience large local reaction later having systemic
reactions is no greater than that of people not experiences
large local [63], [65], [66].
TABLE 4
Normal and allergic reaction to insect stings, as
cited by [42].
Case of allergic
Symptoms
Normal, non-allergic
reaction at the time
of the sting
Pain, sometimes sharp and piercing
Burning, or itching burn
Readiness (erythema) around the sting site
A wide area (wheal) immediately
surrounding the sting puncture mark
Swelling (edema)
Tenderness to touch
Normal, non-allergic
reaction hours or
days after sting
Itching
Residual readiness
A small brown or red damage spot at the
puncture site
Swelling at the sting site
Large local reaction
Massive swelling (angioedema)around the
sting site
Extending over an area of 10 cm or more
and frequently increasing insize 24 to 72
hours, sometimes lasting up to a week in
duration
Cutaneous allergic
reaction
Urticaria (hives, nettle rash) anywhere on
the skin
Angiodema (massive swelling) remote
from the sting site
Generalized pruritis (itching) of the skin
Generalized erythema (redness) of the skin
remote from the sting site
Non life-threatening
systemic allergic
reaction
Allergic rhinitis or conjunctivitis
Minor respiratory symptoms
Abdominal cramps
Severe gastrointestinal up set
Weakness
Fear or other subjective feeling
life-threatening
systemic allergic
reaction
shock
Unconsciousness
Hypotension or fainting
Respiratory distress (difficulty in
breathing)
Laryngeal blockage (massive swelling in
the throat)
5.2 Allergy Test
As cited by [7], [8] stinging the patient with live bees
should be done under medical care and by prescription
from a doctor. It also will need to have a bee sting kit
(epinephrine and antihistamine) available, this kit you
can get it by prescription from your doctor. Be sure you
read the directions on the package before you get your
test sting [7]. The allergy test should be done by giving
the person who will receive the bee venom for healing
with only one sting by a live bee, either direct sting or just
scrape it on his/her skin. The stinger should be remove
immediately after stung, just leave it for about 10
seconds, it is often done on the knee, because it is far
away from the heart and wait for the body reaction [7]. If
no allergic reaction develops 15-20 minutes after stung,
the bee stings is continued, but in case allergic reaction
happened, the person shouldn’t use bee stings for
treating and should avoid exposure to honey bees stings.
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 6
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Copyright © 2012 SciResPub.
6 MEDICAL USES OF BEE VENOM
While apitherapy encompasses use or consumption of
bee products, in the Anglosphere the term is most
commonly associated with bee venom therapy and not
the consumption of honey or other bee products. Due to
its anticoagulant and anti-inflammatory properties BV
was mainly used to treat many inflammatory disorders
such as arthritis, bursitis, tendinitis, dissolving scar tissue
(e.g. keloids), Herpes zoster, joint disease, and
rheumatoid arthritis [2], [69], [1], [3], [70], [71], [72], [73],
[8], [74], , Lyme disease [75], Multiple Sclerosis and
osteoarthritis [76], [77]. Furthermore, research in various
animal experimental models with inflammatory diseases
demonstrated that BV administration was successfully
effective in suppressing the inflammation. [78], [71], [72],
[79], [80], [78], [81]. Interestingly, BV administration
through acupuncture point (acupoint) was proven
successful for producing a strong therapeutic effect as
compared injection to non-acupoint area [78].
Testimonials and observations indicating the
effectiveness of bee venom are common throughout
Western and Asian cultures [82], [83], [84], [85], [86]
discovered that daily injection of 1 mg/kg of bee venom
into rats reduced formaldehyde-induced arthritis in the
foot pad. In another rat model in which Mycobacterium
was the inducer of inflammation, intraperitonal injection
of 1 mg of bee venom inhibited the arthritic effect whom
given daily [9]. [87] stated that bee venom is a method for
treating arthritis.
When a bee stings, it doesn't normally inject all of the
0.15 to 0.3 mg of venom held in a full venom sac [10], [18],
only when it stings an animal with skin as tough as ours
will it lose its sting - and with it the whole sting
apparatus, including the venom sac, muscles and the
nerve centre. These nerves and muscles however keep
injecting venom for a while, or until the venom sac is
empty. The loss of such a considerable portion of its body
is almost always fatal to the bee [8]. Used in small doses
however, bee venom can be of benefit in treating a large
number of ailments. This therapeutic value was already
known to many ancient civilizations. Today, the only uses
of bee venom are in human and veterinary medicine [8].
Bee venom contains 18 different compounds that all
possess pharmaceutical properties. [88] reported that bee
venom, its peptides melittin, and apamin, but not venom
phospholipase suppress edema, probably through an
immunosuppressive. The immunosuppressive effect of
bee venom in rats was confirmed when high dose of bee
venom were injected daily [71]. Whole bee venom and the
peptide melitin experimentally lowered the cycle
adenosine monophosphate (cAMP), an intra-cellular
mediator, in mouse skin and whole venom and
phospholipase caused a dramatic increase in
prostaglandin E levels in that tissue [89], [90]. Bee venom,
particularly the peptide apimen, also exerts an anti-
complement activity in rats [91]. In humans, bee venom
inhibits superoxide production by human neutrophils,
thereby acting as anti-inflammatory activities of bee
venom. [8] stated that the most abundant active
component of the venom is melittin, which has many
useful properties, including powerful anti-inflammatory,
anti-bacterial and anti-viral actions. However, bee venom
is a complex mix of a variety of peptides and proteins,
some of which have strong neurotoxic
and immunogenic effects. There is no standardized
practice for the administration of bee venom. Some
purport that the location of the sting is important, with
the sting acting as a sort of acupuncture in combination
with the effects of the venom, while others report the
location is not important. The number of stings also
varies widely from a few to hundreds and they may be
administered either by live bees or by injection. This
treatment can cause pain, and even result in death if the
subject has an allergy to bee venom, which can
produce anaphylactic shock [8].
As cited by [8] the apamine, melittin, phospholipase,
and hyaluronidase in bee venom have the ability to block
or inhibit the nervous system, stimulate the heart and
stimulate the adrenal glands. The other compounds that
comprise bee venom include formic acid, hydrochloric
acid, ortho-phosphoric acid, mineral substances and
volatile organic acids. Also present are some antibiotics,
phospholipase A, as well as two amino acids rich in
sulfur methionine and cystine. Sulfur is believed to be the
main element in inducing the release of cortisol from the
adrenal glands and in protecting the body from
infections. The mechanism by which all the components
of bee venom might work together to alleviate symptoms
is unknown. Contact with bee venom produces a complex
cascade of reactions in the human body. Homeopaths
theorize that bee sting therapy stresses the body's
immune system, thus getting it to come back stronger.
The active portion of the venom is a complex mixture
of proteins, which causes local inflammation and acts as
an anticoagulant. The main component of bee
venom responsible for pain in vertebrates is the toxin
melittin; histamine and other biogenic amines may also
contribute to pain and itching [93].
As cited by [8] the list of benefits to human beings as
well as to animals is very long. Most of the reports of
cures are of individual cases, though several unrelated
patients have experienced the improvement or cure of
similar ailments. Bee venom treatments are often
accompanied by changes in life style, nutrition or other
which may account for part, if not most of the benefits
from treatments. The diseases and problems which have
been reported by patients or doctors as improved or
healed with bee venom therapy are listed in (Table 5). [8]
stated that this does not constituent an endorsement or
recommendation for the treatments. On the other hand
stinging should never be tried unless there is immediate
access to emergency treatment in case of an allergic
reaction.
[94] stated that bee venom has long been used in
traditional medicine for the treatment of various kinds of
rheumatism. Although venoms of the different honeybee
species differ slightly, there have been reports of
successful rheumatism treatment with Apis dorsata venom
by and with A. cerana venom.
TABLE 5
List of diseases and health problems improved or healed
according to anecdotal reports, as cited [8].
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 7
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Copyright © 2012 SciResPub.
a [76], [77], [107], b [123], c [124], e [125], g [126], h [127].
[95] conducted study to investigate bee venom and
hyaluronic acid in the intra-articular treatment of
osteoarthritis in an experimental rabbit model. They
found that a significant difference was observed in the
HA group (P < 0.05). The MRI evaluation of at any time
in group BVI (b) was found to be different. No significant
differences were seen between the groups, biochemically.
Histopathologically, cellularity, and orthochromasia was
evident with Safranin-O in the BVI (b) and BVII (a);
adhesions were seen in the BVII (a) group and clustering
of chondrocyte in the HA (b) group were found to be
different. Consequently, intra-articular application of HA
and BV for experimental model of osteoarthritis has no
significant influence upon recovery after therapy.
The first step in treatment following a bee sting is
removal of the stinger itself. The stinger should be
removed as quickly as possible without regard to
method: studies have shown the amount of venom
delivered does not differ whether the sting is pinched or
scraped off and even a delay of a few seconds leads to
more venom being injected [96]. Once the stinger is
removed, pain and swelling should be reduced with a
cold compress [97]. Many traditional remedies have been
suggested for bee stings including damp pastes of
tobacco, salt, baking
soda, papain, toothpaste, clay, garlic, urine, onions, aspiri
n or even application of coppercoins [98]. [97] concluded
that ice alone is better treatment for bee and wasp stings
than aspirin.
The sting may be painful for a few hours, swelling and
itching may persist for a week. The area should not be
scratched as it will only increase the itching and swelling.
If a reaction persists for over a week or covers an area
greater than 7-10 cm (3 or 4 inches), medical attention
should be sought. Doctors often recommend
a tetanus immunization. For about 2 percent of
people, anaphylactic shock from certain proteins in the
venom can be life-threatening and requires emergency
treatment [110]. If the victim is allergic to bee stings, the
victim must be treated to prevent shock. People known to
be highly allergic may carry around epinephrine in the
form of a self-injectable EpiPen for the treatment of
an anaphylactic shock.
For patients who experience severe or life threatening
reactions to insect stings, researchers have developed a
series of allergy injections composed of increasing
concentrations of naturally occurring venom which
provide excellent and usually life-long protections
against future insect stings [99].
7 TECHNIQUE
Bee venom therapy is practiced by healthcare
providers and apitherapists who follow certain treatment
protocols. The therapy starts with the determination of
whether the patient is allergic to the venom by
administering a small amount of venom intradermally. If
no allergic reaction develops, the therapy is continued
with the administration of one or two injections. The
therapy is carried out every other day by gradually
increasing the number of bee stings or injections. The
length of treatment is determined by the condition that is
being treated.
Traditionally, live bees that were stimulated to sting
the affected area, trigger points or acupuncture points
were used in bee venom therapy. Depending on the
disease that is being treated, bee venom can be used in a
cream, liniment, ointment or injection form. However,
bee venom is thought to be most effective when it comes
directly from a live bee during the late spring to early fall
season. This season provides the bee with a good pollen
source, allowing the bee to provide more potent venom.
While venom from a live bee is the most potent source of
venom, the injectable form of venom is most commonly
used. A qualified health professional typically injects a
venom solution prepared from pure bee venom
intradermally, just between the skin layers, or
subcutaneously, under the skin, to imitate the effect of a
bee sting.
8 SCIENTIFIC EVIDENCE
Over 1700 scientific publications on the composition
and various effects of bee venom in animals and humans
have been published. An overwhelming proportion
comes from Eastern Europe and Asia [8]. Most of them
concentrate on demonstrating the site specific,
physiological effects of individual components such as
membrane destruction, toxicity, or the stimulation or
blocking of enzyme reactions, the physiological effects of
isolated venom compounds and the substances
responsible for most of the allergic reactions. It has
contributed little to verifying the increasing claims of
different therapeutic values attributed to honeybee
venom. A study with whole bee venom on dogs [12], and
rats [100] showed that melittin and apamine produce
increased plasma cortisol. Together with various other
arguments, this suggests that many of the curative effects
of bee venom may work through stimulation of the
body's enzyme and immune system, in a way similar to
the common drug cortisone. Cortisone has been used in
the treatment of many ailments, but it is also known to
have strong, undesirable side-effects. Melittin also
Humans
Arthritis, many typesa
Multiple
sclerosisa
Premenstrual
syndromea
Epilepsya
Bursitisa
Ligament injuriesa
Mastisa
Some types of
cancera
Sore throata
Chronic paina
Migraineb
General immuno-
stimulant
Decreases blood
viscosity and
coagulabilityb
Dilates
capillaries and
arteriesb
Decreases blood
cholesterol levelb
Neruosesb
Rhinosinusitis
c
Endoarteriosisd
Therosclerosisd
Polyneuritise
Radicultitisef
Infectious spondylitise
Neuralgiae
Endoarthritise
Infect. Polyarthritise
Malariae
Intercostal myalgiaf
Myositisf
Tropical
ulcersf
Slowly healing
woundsf
Thrombophiletritisf
Cancer,
temporaryf
Keratoconjunctivitisg
Iritisg
Iridocytisg
Asthmah
Animals
Arthritis
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 8
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Copyright © 2012 SciResPub.
appears to have toxic side effects as do some of the other
individual compounds in venom. When whole venom is
applied however, no side-effects have been shown, other
than in allergic patients [84]. The anti-inflammatory
effects of bee venom are perhaps the best studied and the
various mechanisms have been repeatedly described in
scientific literature [102]. The neurotoxic venom
compounds have shown a potential benefit for epileptic
patients [103]. The protective value of bee venom and
melittin against the lethal or damaging effects of x-rays
has been investigated [104], [134]. Recently, after long
efforts by the American Apitherapy Society and its
members, some interest has been shown by national
institutions in several Western European countries and
the USA for clinical and large scale tests of bee venom
therapy.
As cited by [8] a good summary of the scientific
studies, with further references can be found in [20], [11].
Summaries of some of the major specific effects of the
various venom compounds that are shorter and more
easily understood, can be found in [60], [19], [18], [105].
The American Apitherapy Society keeps records of
scientific as well as anecdotal information on the use of
bee venom. It is also probably the best source of
information on any subject related to apitherapy.
9 VENOM PRODUCTS
No uses for venom, other than medical ones are
known [8]. The only legally accepted medical use of bee
venom in Western European and North American
countries is for desensitizing people who are
hypersensitive (allergic) to bee venom. Since the early
1980's, pure bee venom has been used for desensitization.
The use of whole body extracts has been largely
discontinued after a double-blind test proved the higher
efficiency of pure venom [106]. In Eastern Europe and in
many Asian countries bee venom has been used in official
medical treatment of a large variety of ailments for a
considerable length of time.
The use of pure venom injections and well placed bee
stings is increasing in Western countries as an alternative
to heavy (and sometimes ineffective) drug use, which is
often associated with numerous side-effects. This is
particularly so for arthritis and other rheumatoid
inflammations. Application methods for venom include
natural bee stings, subcutaneous injections,
electrophoresis, ointments, inhalations and tablets [94].
Bee venom may be sold as whole bee extract, pure
liquid venom or an injectable solution, but in either form
the market is extremely limited. Most venom is sold in a
dry crystalline form. Depending on the disease that is
being treated, bee venom can be used in a cream,
liniment, ointment or injection form. Bee venom solutions
are also used in Europe and China with electroporesis or
ultrasonophoresis.
For injections, the venom can be mixed at the time of
injection with injectable fluids, such as distilled (sterile)
water, saline solutions and certain oils, or it may be taken
from prepared ampoules. Ampoules with set doses of
ready-to-inject venom should only be prepared by
certified pharmaceutical laboratories, because of the need
to maintain stringent aseptic conditions and to measure
the dosages very precisely [8].
There are creams available which include bee venom
(e.g. Forapin and Apicosan in Germany, Apivene in
France and Immenin in Austria) which are used for
external application on arthritic joints [107], [94]. Bee
venom therapy can also be delivered in the form of Bee
Venom Balm although this may be less potent than using
live bee stings [8].
Tablets can be impregnated with quantities of bee
venom, but [94] recommended the removal of toxic
proteins, such as Melittin and the use of colours to
indicate different dosages. The tablets should be placed
under the tongue, but no indication is given to the effect
or usefulness of such a preparation.
Some specialized laboratories may be able to separate
and purify different venom compounds and sell them to
scientific and pharmaceutical laboratories. Phospholipase
A2 and highly active peptides are among some of the
proteins purified from bee venom for scientific suppliers
or laboratories [105]. Entry to this limited market requires
a highly sophisticated laboratory and very well-trained
technicians and chemists.
Ointments can be prepared by thoroughly
homogenizing bee venom with white Vaseline,
petrolatum or melted animal fat, and salicylic acid, in the
ratio of 1:10:1. The salicylic acid softens the skin, increases
its permeability and is a treatment for rheumatism even
on its own. The ointment may contain a small amount of
silicate crystals to act as an abrasive [94]. Other
preparations consist of mixing bee venom with sterile,
injectable fluids and packaging them in single dosages in
glass vials or syringes. In some packages the dry venom
is kept separate from the fluid and the two are mixed
when the vial is broken [8].
Though not directly related, bee sting emergency kits
can be sold in some countries, particularly to people who
are allergic. They also should be at hand for any
beekeeper working with honey bees or Africanized
honeybees and at training centres, police and fire
departments, in areas with Africanized honeybees. In the
USA, they are now available only against a prescription.
Such a kit (e.g. Anakit by Hollister Stier, USA, as cited by
[8]) should contain at least: One syringe with a
premeasured content of epinephrine (adrenaline) or
atropine, for immediate intramuscular injection - usually
0. 3 m1 of a diluted solution of epinephrine (1:1000) in
saline solution. There are special, easy-to-use, syringes
available from bee supply houses or through pharmacies,
which can even be used through clothing (Epipen by
Centre Laboratories, USA); anti-histamine tablets;
tourniquet and instructions about when, where and how
to use the syringe and anti-histamine tablets; when not to
use epinephrine, and where to seek medical help.
Epinephrine injections should be given only in extreme
emergencies when no other medical help is available. The
sting emergency kit has a limited shelf-life and should be
kept refrigerated when not in use.
10 BUYING AND STORAGE THE BEE VENOM
As cited by [8] the best way to buy bee venom is in the
crystallized form, since it is more stable, impurities are
easier to detect and adulteration is less likely. The colour
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 9
ISSN 2278-7763
Copyright © 2012 SciResPub.
of both crystals and powder should be a very light
yellow. Liquid venom should be clear and colourless.
Darker venom is slightly oxidized and may have lost
some of its effectiveness. As with all other products
where immediate testing is not possible or is very
expensive, the producer should be one who is well-
known and who can be trusted to produce a high quality
product. The producer as well as the buyer should have
adequate storage facilities.
Even dried bee venom should be stored refrigerated or
preferably frozen and it should always be kept in dark
bottles in the dark. All producers and buyers should
closely observe these conditions. Dried bee venom can be
kept frozen for several months, but should not be kept
refrigerated for more than a few weeks. Liquid venom
and diluted venom can be stored for similar periods if
maintained in well sealed, dark glass containers [8].
11 QUALITY CONTROL OF BEE VENOM
As cited by [8] there are no official quality standards,
since bee venom is not recognized as an official drug or as
a food. Purity analysis may be carried out by quantitative
analyses of some of its more stable or more easily
measured components such as melittin, dopamine,
histamine, noradrenaline or those for which
contamination is suspected. A nematode, Panagrellus
redivivus was reported to react selectively and
specifically to bee venom and a quantitative analysis of
the venom in pharmaceutical preparations was
developed by [108] using this organism. [51] describes a
method for testing the biological activity of bee venom by
measuring electric pulses from muscles of excised
honeybee abdomens in response to the volatile materials
from bee venom. [109] described standardization and
quality control methods for purity and effectiveness of
Hymenoptera venom, including honeybee venom.
12 SAFTY OF BEE VENOM
The median lethal dose (LD50) for an adult human is
2.8 mg of venom per kg of body weight, i.e. a person
weighing 60 kg has a 50% chance of surviving injections
totaling 168 mg of bee venom [10]. Assuming each bee
injects all its venom and no stings are quickly removed at
a maximum of 0.3 mg venom per sting, 560 stings could
well be lethal for such a person. For a child weighing 10
kg, as little as 93.33 stings could be fatal. Therefore, quick
removal of the stings is important. However, most human
deaths result from one or few bee stings due to allergic
reactions, heart failure or suffocation from swelling
around the neck or the mouth.
Table (6) shows the number of honey bee stings that
can cause death 50% of individuals exposed to bee stings
on the basis of body weight as cited by [8]. In case of a
child weighing 10 kg, about 93.33 or 186.67stings could
well be lethal for such a child assuming each bee injects
0.30 or 0.15 mg venoms, for a person weighing 60 kg,
about 560 or 1120 stings could well be lethal for such a
person assuming each bee injects 0.30 or 0.15 mg venoms
(Table 6).
TABLE 6
The number of honey bee stings that can cause death 50%
of individuals exposed to bee stings on the basis of body
weight (the median lethal dose (LD50) for an adult
human is 2.8 mg of venom per kg of body weight. and the
bees secretes 0.15 0.30 mg), as cited by [42].
Body
weight
(Kg)
The
(LD50) for
an adult
human is
2.8 mg of
venom per
kg of body
weight
Number of honey bee stings
needed for LD50 for humans in
case honey bee worker secretes
0.3 mg
venom
0.15 mg venom
10
28
93.33
186.67
20
56
186.67
373.33
30
84
280
560
40
112
373.33
746.67
50
140
466.67
933.33
60
168
560
1120
70
196
653.33
1306.67
80
224
746.67
1493.33
90
252
840
1680
100
280
933.33
1866.67
110
308
1026.67
2053.33
120
336
1120
2240
It is theoretically estimation depending on the bee worker
secretes (0.15 0.30 mg venom) and, the median lethal
dose (LD50) for an adult human is 2.8 mg of venom per
kg of body weight [10].
On the other hand the bee venom is very safe for
human treatments as compare with other human
diseases, accidents and other unusual cases. Table (7)
shows the statistics of the rates of death to humans
caused by diseases, accidents and other unusual cases in
the United States in 1986 as cited by [42], out of 2086440
death in the year 1986 in the USA 977700 cases died by
heart diseases acts as (46.86%) from the total death. The
total number of death caused by cancer was 641400
(30.74%), by the smoking 150000 cases (7.19%), by asthma
3880 cases (0.186%), by allergy to penicillin 300 cases
(0.014%), by insect bites (not honey bees) 24 cases
(0.0012%), meanwhile by honey bees stings 17 cases
(0.0008%).
Although, bee venom is safe for human treatment, it
should only be used under the supervision of a qualified
health care professional. Most experts recommend having
an emergency sting kit available in case of allergic
reaction. This kit should include a syringe and a dose of
epinephrine and antihistamine tablets. It is also advisable
that a test sting be performed before undergoing a
treatment. There may be some discomfort associated with
the administration of bee venom. This may include pain,
itching, swelling, inflammation and redness at the
injection site. More severe reactions may also occur.
TABLE 7
Statistics of the rates of death to humans caused by
diseases, accidents and other unusual cases in the United
States in 1986 (as cited by [42]).
Cause of death
the
Death
the percentage
International Journal of Advancements in Research & Technology, Volume 1, Issue2, July-2012 10
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Copyright © 2012 SciResPub.
number
of
deaths/
year
rate per
1,000,00
0/ year
of the death of
the total
deaths
Heart disease
977700
4096
46.8597
Cancer
641400
1933
30.7414
Smoking
150000
750
7.189
Abuse Alekhalaat
100000
500
4.7929
Car accident
45601
192
2.1856
Suicide
29453
123
1.4116
Murder
19628
83
0.9407
Radon Gas
13000
54
0.6231
Foot vehicle
7641
32
0.3662
Drowning
4407
18.4
0.2112
House fires
3964
16.6
0.1900
Asthma
3880
16.2
0.1860
Poisoning
3621
15.1
0.1735
incidents of firearms
1649
6.9
0.0790
Freezing
1010
4.2
0.0484
Incidents of
electricity
802
3.4
0.0384
Slip and silence
while walking
404
1.7
0.0194
Allergy to penicillin
300
1.5
0.0144
Hunger and thirst
195
0.82
0.0093
Silent during
Horseback riding
108
0.45
0.0052
Biting animals
(dogs, etc.)
101
0.42
0.0048
Lightning
85
0.36
0.0041
During a collision
sport
42
0.18
0.0020
Stress overload
28
0.17
0.0013
Insect bites (not
honeybees)
24
0.07
0.0012
Honey bee sting
17
0.12
0.0008
Total deaths
208644
0
8739
100%
a [128], b [129], c [130], d [131], e [42].
13 CONCLUSION
Use of honey and other bee products in human
treatments traced back thousands of years and healing
properties are included in many religious texts including
the Veda, Bible and Quran. Apitherapy is the use of
honey bee products for medical purposes, this include
bee venom, raw honey, royal jelly, pollen, propolis, and
beeswax. Whereas bee venom therapy is the use of live
bee stings (or injectable venom) to treat various diseases
such as arthritis, rheumatoid arthritis, multiple sclerosis
(MS), lupus, sciatica, low back pain, and tennis elbow to
name a few. It refers to any use of venom to assist the
body in healing itself. The bee venom contains 88% water.
The glucose, fructose and phospholipid contents of
venom are similar to those in bee's blood. At least 18
pharmacologically active components have been
described, including various enzymes, peptides and
amines. The main component of bee venom responsible
for pain in vertebrates is the toxin melittin; histamine and
other biogenic amines may also contribute to pain and
itching. Melittin comprising 52% of venom peptides. The
melittin is a strong anti-inflammatory agent and induces
the production of cortisol in the body. Apamin increases
cortisol production in the adrenal gland. Apamin is a
mild neurotoxin. Adolapin, comprising 2-5% of the
peptides, acts as an anti-inflammatory
and analgesic because it blocks cyclooxygenase.
Phospholipase A2 comprises 10-12% of peptides and it is
the most destructive component of apitoxin. It is
an enzyme which degrades the phospholipids which
cellular membranes are made of. It also causes
decreased blood pressure and inhibits blood coagulation.
Phospholipase A2 activates arachidonic acid which is
metabolized in the cyclooxygenase-cycle to
form prostaglandins. Prostaglandins regulate the body's
inflammatory response. Venom from other Apis species is
similar, but even the venoms from the various races
within each species are slightly different from each other.
The toxicity of Apis cerana venom has been reported to be
twice as high as that of A. mellifera. The bee venom is safe
for human treatments, the median lethal dose (LD50) for
an adult human is 2.8 mg of venom per kg of body
weight, i.e. a person weighing 60 kg has a 50% chance of
surviving injections totaling 168 mg of bee venom.
Assuming each bee injects all its venom and no stings are
quickly removed at a maximum of 0.3 mg venom per
sting, 600 stings could well be lethal for such a person.
For a child weighing 10 kg, as little as 90 stings could be
fatal. Therefore, quick removal of the stings is important.
However, most human deaths result from one or few bee
stings due to allergic reactions, heart failure or
suffocation from swelling around the neck or the mouth.
As compare with other human diseases, accidents and
other unusual cases, the bee venom is very safe for
human treatments.
ACKNOWLEDGMENT
My deep respect and my deep thanks for our God for
giving us honey bees. My thanks also go to all the
scientists whom conducted research in this area,
especially those whom provided me their original papers
or their books.
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Copyright © 2012 SciResPub.
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... The most important enzyme components are phospholipase A2, hyaluronidase, acid phosphomonoesterase, lysophospholipase, and α-glucosidase. Also, it includes physiologically active amines (e.g., histamine, dopamine, noradrenaline), amino acids (i.e., aminobutyric acid), carbohydrates, phospholipids, lipids, and volatile compounds [4]. Melittin, which constitutes about 50-60% of BV, acts as a robust anti-inflammatory agent in minimal doses by inducing cortisol production in the body but may cause adverse effects (e.g., inflammation, pain, and itching) in high doses. ...
... Apamin with about 1-3% of BV acts as a mild neurotoxin after entering the body, increasing the production of cortisol in the adrenal gland. Adolapin, comprising 2-5% of the peptides of BV, has cyclooxygenase blocking properties and acts as an anti-inflammatory and analgesic agent [4]. ...
... Due to BV's extensive biological properties, bee venom therapy (BVT) has been applied in medicine to treat autoimmune diseases such as multiple sclerosis [4]. Furthermore, its antiinflammatory and immunosuppressive properties make it special for treating rheumatoid arthritis patients like acupuncture in different clinical trials [5]. ...
Article
Full-text available
Objectives: Bee venom (BV) therapy is performed by a bee sting or subcutaneous injection of BV. However, there is not much information on the effect of BV on blood parameters after entering the body. This project aimed to assess the side effects of subcutaneous BV injections in healthy rats by measuring the hematological and biochemical parameters. Methods: Various amounts of BV, including 100, 200, and 500 (µg/day), were subcutane-ously injected into rats for 30 days. The results showed that BV affected the metabolism of the liver, kidney, and glands. Results: An increase in blood sugar and a decrease in other biochemical parameters, including cholesterol, triglyceride, urea, creatinine AST, ALT, ALP, and phosphorous, were observed. Results also showed increased counts of white blood cells, neutrophils (%), and platelets and decreased levels of red cells, hemoglobin, and hematocrit. Conclusion: This study demonstrates that BV therapy in medical clinics requires routine care and testing to prevent eventual metabolic and anemia side effects.
... From the perspective of previous studies, the study focused on the potential and negative impacts of BVT treatment, which can be seen through (Zhang et al., 2008;Ali, 2012;Köhler et al., 2014). However, the present study differs from previous studies where it will examine the BVT treatment method performed by traditional medical practitioners in Malaysia and analyse it from the ethical point of Islamic treatment. ...
... There are reports that an older woman dies after receiving BVT treatment (Vazquez-Revuelta & Madrigal-Burgaleta, 2018). Besides, according to Ali's (2012) study, there is a significant relationship between venom content with age at which children and older persons are exposed to higher risk than healthy and young people. ...
... This is mentioned in the hadith which means, whoever treats a person (becomes a doctor) and does not know the science of medicine, he is responsible (for the consequences to the patient) (Abu Dawud, 2009). This practice also contradicts to conventional medical practice which emphasises that expert opinion should be obtained before any treatment is done in order to ensure the effectiveness and to avoid allergies-sideeffects possibilities, especially when dealing with venom-based-medicine (Ali, 2012). According to Vazquez-Revuelta and Madrigal-Burgaleta (2018), knowing the side effects of BVT is crucial as it can lead to the risk of death if the treatment is not compatible with the disease or might causes allergy to the patient. ...
Article
Full-text available
Bee venom therapy (BVT) is one of the ancient traditional treatments. BVT is believed as capable to cure a variety of diseases despite of having significant negative impacts upon its usage. However, the BVT method has raised questions as Islam forbids the killing of bees as a result of getting its venom, as well as the use of venom as a treatment method. Therefore, this study was conducted to examine the BVT practices from the standpoint of Islamic ethics. Data collected through a triangulation of document analysis and unstructured interviews with three BVT practitioners. The findings found two major ethical issues of BVT. First, the practitioners are not aware that killing bees is contrary to Islamic ethics and the BVT should be the last option to be used if there is no other treatment works for the diseases. Second, several practitioners are not qualified to carry out medical procedures due to the lack of medical knowledge and unawareness about the risk of the treatment for a certain group of people. Therefore, this study suggests BVT practitioners, especially Muslim to follow Islamic ethics when performing BVT to reduce any possible risk.
... The stinger has evolved from the laying apparatus and only females are able to sting. BV is a complex material produced by the poisonous gland located in the abdominal cavity (Ali, 2012). ...
... Primitive men learned to look for hives and were certainly the first to receive apitherapy due to bee stings. Honey has been used for thousands of years, as observed in several religious texts including the Veda (Hindu scriptures), Quran and the Bible (Ali, 2012). ...
... BV is a transparent liquid utilized for the defense of the hive. Its composition comprises biologically active molecules like melittin, apamine, phospholipase 2, histamine, dopamine, norepinephrine, and others (Ali, 2012;Oršolić, 2012). ...
Article
Full-text available
Background Humanity has benefited from bee products over the centuries for treating and preventing various illnesses, and apitherapy has been employed in several countries as a complementary medicine. This review aimed to discuss scientific research and clinical trials using bee products and their relationship with apitherapy. Methods Scientific researches based on studies carried out in vitro using different cell cultures, and in vivo studying mice or other experimental animals are discussed. Clinical trials using bee products are also documented. Results The most common applications of bee products in apitherapy are presented, as well as cases of allergy to bee products and apitherapy for treating allergies. Standardization of bee products and their use in research and apitherapy are discussed. Conclusion Apitherapy is practiced in some parts of the world, bringing benefits for healthy individuals and patients, with no clear consensus on its application according to the world regions or a prevalent use of bee product and treated disease. Different recommendations regarding the use of bee products are found and people ingest different amounts of bee products once or several times a day. Although we have advanced a lot about the knowledge of bee products, it is imperative to exploit their potential and standardize their use, communicating the results in scientific and alternative events to reinforce the exchange of information between beekeepers, researchers, apitherapists, nutritionists, physicians, sellers and consumers of bee products. If not, we will always be working separately, without complementing our expertise.
... Three components of HBV, Melittin, Apamin, and PLA2, are considered important quality indicators for their essential bioactivities suitable for apitherapeutic or cosmetics purposes (Banks & Shipolini 1986). Among these constituents, melittin has been reported to be the major component of bee venom ranging between 40-50%, as reported by many studies (Ali, 2012;Banks & Shipolini, 1986;Bogdanov, 2015;Kye-Sung & Ki-Rok, 2009;Moreno & Giralt, 2015;Zhou et al., 2010;Samancı & Kekeçoğlu, 2019). On the other hand, some studies proclaimed much higher or lower values of melittin. ...
Article
Full-text available
Honeybee venom (HBV) is an important product of beehives, and its benefits for health have been rediscovered by modern medicine. Since HBV has the potential to treat some diseases, its quality and production conditions require a detailed investigation. The objective of this study is to understand how season, harvesting time (day or night), harvesting site of beehives (inside or entrance) and geographic location affects quality through the analysis of apamin, melittin and phospholipase A 2 (PLA2) content. Each set of six colonies were used to understand the differences in these components when HBV is harvested in the daytime either from the entrance or inside of the hives and nighttime from the inside of the hives. The experiment also investigated seasonal differences as the samples were harvested each month from May to August 2019 in our apiary. Furthermore, the effect of geographic location on quality was examined through the comparison of the data obtained from twenty-seven samples collected by beekeepers using the same device, located in the Turkish cities of Manisa, Muğla, Balıkesir, Düzce and Mersin. The results demonstrated that statistically significant differences in the amounts of analyzed components were not dependent on harvesting time, collection site on the beehives or season. On the other hand, region samples significantly differed in the amounts of all three components, ranging from 1.28% to 3.81% for apamin, 19.51–64.03% for melittin and 7.22%–28.18% for PLA2. However, beekeepers’ improper practices during harvesting and storing might be the most critical parameters that determine the quality of HBV.
... It contains different active compounds, including peptides (melittin, apamin, adolapin), enzymes (for example, phospholipase A 2 ), amines (for example, epinephrine and histamine), and minerals. The composition of the venom is 88% water and only 0.1 µg dry venom [5,52,53]. More details about the chemical content of bee venom, its biological properties, and mechanisms of action are given in a review by Wehbe et al. [5]. ...
Article
Full-text available
Apitherapy is a form of alternative therapy that relies on the use of bee products, i.e., honey, royal jelly, propolis, pollen, and bee venom (known as apitoxin), for the prevention and treatment of various diseases. Various in vitro and in vivo studies suggest that these products may be effective in the prophylaxis and treatment of cardiovascular diseases (CVDs). This mini-review of papers identified in various electronic databases describes new aspects of the bioactivity of certain bee products, viz. bee pollen, royal jelly, bee venom, propolis, and bee bread, as natural interesting products for the prevention and treatment of common CVDs.
... Arı zehiri, bazıları güçlü immünojenik ve nörotoksik etkilere sahip çeşitli protein ve peptitlerin bir karışımıdır. 39 Apitoksin olarak da bilinen arı zehiri geleneksel olarak halk tıbbında ağrıyı hafifletmek, artrit ve romatizma gibi enflamatuar hastalıkları tedavi etmek için kullanılmıştır. Eskiden beri halk arasında direk olarak arının sokması şeklinde kullanılırken günümüzde arılardan elde edilen arı zehirinin farmasötik olarak kullanımı da mümkündür. ...
Chapter
Full-text available
Apiterapinin tarihi antik çağlara kadar dayanmaktadır ve günümüzde halen halk tıbbında sıklıkla tercih edilmektedir. Apiterapi, bal arısı Apis mellifera L.’nın ürünleri olan bal, propolis, polen, arı ekmeği, arı sütü, arı zehiri ve bal mumunun, hastalıklara karşı koruyucu veya terapötik amaçla kullanılmasıdır. Geçmiş yıllarda sadece balın besleyiciliği ve takviye edici gıda olarak kullanılması bilinmekteyken, artık günümüzde apiterapi ürünleri ve bu ürünlerle yapılan bilimsel araştırmalar çeşitlilik göstermiştir. Yüksek oranda polifenolik bileşik içeren apiterapi ürünlerinin vücutta çeşitli hastalıklar üzerinde etkili olduğu ve sağlık için faydalı olduğu kabul görmektedir. Apiterapi ürünleri, ürünün türüne, kullanım şekli ve dozuna bağlı olarak birçok farmakolojik etkiye sahiptir. Bu ürünlerin içerdiği biyoaktif moleküller sayesinde antimikrobiyal, antikanserojen, antiinflamatuvar etkilerini konu alan yapılmış preklinik ve klinik araştırmalar bulunmaktadır. Sahip olduğu farmakolojik etkileri sebebiyle apiterapi ürünlerinin geliştirilmesinin toplum sağlığı açısından önemli olduğu ve uygun klinik araştırmaların arttırılmasına ihtiyaç duyulduğu anlaşılmaktadır. Bu derlemede apiterapi ürünlerinin farmakolojik özellikleri ve insan sağlığına etkileri üzerinde durulmuştur.
... Bee venom is effective in treating pain and has recently been applied to various diseases such as arthritis, adhesive capsulitis, lupus, and cancer [1][2][3]. Bee venom acupuncture (BVA), one of the most frequently used techniques recently, involves intradermally or intramuscularly administering a small amount of refined bee venom into specific acupoints or painful areas [4]. ...
Article
Full-text available
Background: Bee venom acupuncture (BVA) is an effective treatment method for various diseases. Bee venom, however, can cause adverse effects, even rarely including life-threatening anaphylaxis, so safety-related evidence is required. In this study, we systematically estimated the incidence rate of anaphylaxis in response to BVA. Methods: We searched eight databases (MEDLINE (Pubmed), EMBASE, Cochrane Central Register of Controlled, KISS, KMBASE, Koreamed, OASIS, and NDSL) and systematically reviewed the articles that met the inclusion/exclusion criteria. Results: Among 225 potentially relevant articles, 49 were selected for this study. The overall incidence rate of anaphylaxis in response to BVA was 0.045% (95% CI 0.028-0.062). Women (0.083%, 95% CI 0.010-0.157) showed a higher incidence rate than men (0.019%, 95% CI -0.018 to 0.055), while the incidence for patients who had a skin test conducted (0.041%, 95% CI 0.011-0.072) was not significantly different compared to that obtained for patients for which there was no information about a skin test (0.047%, 95% CI 0.026-0.067). The publication year affected the incidence rate: it was highest before 1999 (1.099%, 95% CI -1.043 to 3.241), lower between 2000 and 2009 (0.049%, 95% CI 0.025-0.073), and lowest between 2010 and 2021 (0.037% 95% CI 0.014-0.060). Conclusions: In this study, we provide reference data about risk size and factors of BVA-related anaphylaxis, which is essentially required for BVA application in clinics.
... Bee venom is a collection of different compounds, such as enzymes, peptides, and physiologic amines. Some of the physiologic amines include hyaluronidase, phospholipase A, phosphatase acid, α-glycosidase, protease inhibitors, melittin, apamin, mast cell degranulating peptides, adolapin, cardiopep, procamine, tertiapin, secapine, histamine, dopamine, and noradrenaline (Ali, 2012;Mammadova and Topchiyeva, 2017). ...
Article
BACKGROUND: Bee venom contains various biomolecules, such as enzymes, peptides, and amines. The immune system produces IgG antibodies against bee venom proteins. However, IgE antibodies may also be developed in allergic individuals. OBJECTIVES: In this study, immune responses, including IgG and IgE reactions to bee venom were assessed in various individuals, using the immunoblotting technique. METHODS: Serum samples were collected from 20 people of three major groups, namely beekeepers, allergic individuals, and normal people. Venom samples of honey bees and wild bees were collected from the suburbs of Tehran, Iran. Furthermore, commercial honey bee venom samples extracted from Apis mellifera and samples of wild bees extracted from Polistes and Vespula were purchased from France. Immunoblotting was carried out using the sera of subjects and antihuman IgG and IgE coupled to horseradish peroxidase. RESULTS: The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed similar protein bands in Iranian and European honey bee venoms, including α-glucosidase (170 kDa), Api m (100 kDa), acid phosphatase (49 kDa), hyaluronidase (43 kDa), phospholipase A2 (17 kDa), and melittin (2 kDa). In wild bees, two bands were found with the molecular weights of 35 and 25 kDa belonging to antigen 5 and phospholipase A1, respectively. These were not observed in honey bee venoms. Immunoblot analysis revealed that all the mentioned proteins were immunogenic and allergenic in different individuals. Hyaluronidase, as well as phospholipases A1 and A2, were the major allergens in most individuals, while IgE reaction to melittin was only reported in one person. CONCLUSIONS: In conclusion, studies on antibodies against bee venoms can be useful in immunotherapy. Different people indicated distinct allergenic patterns. Therefore, further similar assays are recommended before, during, and after immunotherapy.
Chapter
Bee products such as honey, propolis, bee pollen, royal jelly, beeswax, and bee venom constitute important pharmaceutical and cosmetic components. Each bee product is characterized by the content of the active substance, which differentiates one bee product from another, and causes that each of them is worth using for a different skin problem. In addition, flavonoids and phenolic acids play a crucial role in influencing those products on the skin. For example, honey, propolis, and pollen are used to heal burn wounds. Moreover, bee venom called apitoxin contains active peptides and amines used in the wound’s healing process. Therefore, findings connected with wound dressing containing honey, propolis, or bee venom can be applied during wound healing therapy. Furthermore, the advantages of pharmaceuticals and cosmetics based on bee products are high effectiveness with minimal side effects. Therefore, bee products may become a new strategy in skin therapy.
Chapter
Bee venom has gained popularity in some European countries as an antirheumatic drug. Its healing effect has been known from time immemorial. The encouraging therapeutic results obtained by healers who practiced bee stinging as well as the application of modern pharmaceuticals could hardly be accounted for by the scarce pharmacological data on the mechanism of its action. The venom-induced activation of the hypophysocorticorenal system was believed to be the major phenomenon involved (Shkenderov et al., 1968; Shkenderov, 1971). In line with the concept of its anti-inflammatory effect, were the uncoupling of oxidative phosphorylation and the degranulation of mast cells leading to histamine release (Habermann, 1954; Breithaupt and Habermann, 1968). The radioprotective effect of the venom discovered by Shipman and Cole (1967) aroused deep interest but increased the problems about the mechanism of its action. In the meantime, a number of tests and criteria were elaborated for the evaluation of nonsteroid antirheumatic drugs; some tests are related to the pharmacobiochemical bases of their actions.
Article
By introducing a cooling system into an existing apparatus for collecting bee venom, it was possible to obtain large enough quantities of the liquid fraction to facilitate chemical analysis. Gas chromatograms showed at least 13 peaks, one of which is presumed to be iso-amyl acetate. The effect on bees of this substance, and of the liquid fraction now obtained, is described briefly.
Article
The method of venom collection referred to here is illustrated and described briefly on page 68. It was designed for bulk collection, and yields a gram of dried venom in five minutes' ‘milking’ of each, of 20 hives. It is in principle similar to the delicate method described by D. J. Palmer in Bee World in 1961. But its high yields themselves introduce complications, because of the large amounts of ‘alarm odour’ released at the same time as the venom. These complications are discussed here.