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BEE PROPOLIS-A NOVEL PERSPECTIVE

Authors:
  • Vijaya Institute of Pharmaceutical Sciences for Women
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BEE PROPOLIS-A NOVEL PERSPECTIVE
Vani Mamillapalli1*, Vamsi Meghana Tiyyagura1, Mounika Katamneni1 and Padma Latha Khantamneni2
1Department of Pharmacognosy and Phyto Chemistry, Vijaya Institute of Pharmaceutical Sciences for Women,
Enikepadu, Vijayawada, Pin: 521108, Krishna District, Andhra Pradesh, India.
2Department of Pharmacology, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Pin.
521108, Krishna District, Andhra Pradesh, India.
Article Received on 24/09/2018 Article Revised on 14/10/2018 Article Accepted on 05/11/2018
INTRODUTION
Propolis, also called ‗Bee glue‘, is resinous material
collected by Apis mellifera from various tree buds which
they then use to coat hive parts and to seal cracks and
crevices in the hive.[1] It is a multifunctional material
used by bees in the construction and maintenance of their
hives. The word ―propolis‖ is derived from the Greek pro
(for ―in front of‖ or ―at the entrance to‖) and polis
(―community‖ or ―city‖) and means a substance in
defense of the hive. Propolis, or bee glue, is a brownish
resinous material collected by worker bees from the leaf
buds of numerous tree species like birch, poplar, pine,
alder, willow, palm, Baccharis dracunculifolia, and
Dalbergia ecastaphyllum.[2]
Propolis has been used as a folk medicine since 300
BC.[3] Recently, numerous biological properties of
propolis have been reported including cytotoxic,
antiherpes, free radical scavenging, antimicrobial, and
anti-HIV activities.[4] Because of the wide range of
biological activities, propolis has recently been
extensively used in food and beverages to improve health
and prevent diseases.[5] In order to manufacture propolis,
bees may also use material actively secreted by plants or
exuded from wounds in plants.[6]
Propolis has been used by man since early times for
various purposes as an antiseptic, antioxidant, anti-
inflammatory, and an adhesive and to seal cracks; to
protect wooden and other surfaces. Unlike many 'natural'
remedies, it possessesantibiotic, antifungal, antiviral and
antitumour properties. It exhibits allergic reactions, and
is relatively non-toxic.
The bees use propolis to repair combs, to strengthen the
thin borders of the comb, and to make the entrance of the
hive weather tight or easier to defend (Fig.1). Propolis is
also used as an ―embalming‖ substance to cover the
carcass of a hive invader which the bees have killed but
cannot transport out of the hive.[7] The phytoconstituents
composition in the bee propolis varies and depends upon
the flora in the location. More than 500 compounds have
been isolated and identified in bee propolis.[8] Uses of
products containing propolis have resulted in extensive
dermal contact and it is now increasingly being used a
dietary supplement.
Fig. 1: Bee Propolis.
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Review Article
ISSN 2394-3211
EJPMR
EUROPEAN JOURNAL OF PHARMACEUTICAL
AND MEDICAL RESEARCH
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ejpmr, 2018,5(12), 167-171
*Corresponding Author: Vani Mamillapalli
Department of Pharmacognosy and Phyto Chemistry, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Pin:
521108, Krishna District, Andhra Pradesh, India.
ABSTRACT
Honey bees produce a natural resinous mixture called bee propolis. Nowadays, propolis gained increasing
importance as a therapeutic agent in allopathic medicines, homeopathic products and also in cosmetics in various
dosage forms. The chemical composition of propolis varies according to the flora it was collected by bees. Propolis
is commonly used by folk people for its healing, soothing,antiseptic and restorative capabilities in problematic skin.
Bee propolis has also been studied for various biological activities such as antibacterial, antifungal, anti-
hyperglycemic etc. This review discusses about physical and chemical properties, composition, biological
activities, formulations, precautions of using bee propolis. The wide spectrum of therapeutic effects make propolis
a future potential candidate in several clinical scenarios.
KEYWORDS: Propolis, Biological Activities, Composition.
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168
BEE PROPOLIS CHARACTERISTICS
General Characteristics
Propolis is lipophilic in nature, hard, brittle, soft, pliable,
gummy, and very sticky when heated. It possesses a
characteristic, pleasant aromatic smell and varies in color
from yellow green to red and to dark brown depending
on its source and age. Depending on the origin of the
resins, it also ranges from yellow to dark brown. But
even transparent propolis has been reported.[9]
Chemical Composition
Propolis is the third most important component of bee
products. It is composed mainly of resin (50%), wax
(30%), essential oils (10%), pollen (5%), and other
organic compounds (5%).[10] Phenolic compounds, esters,
flavonoids, terpenes, beta-steroids, aromatic aldehydes,
and alcohols are the important organic compounds
present in propolis. Twelve different flavonoids, namely,
pinocembrin, acacetin, chrysin, rutin, luteolin,
kaempferol, apigenin, myricetin, catechin, naringenin,
galangin, and quercetin, two phenolic acids, caffeic acid,
cinnamic acid and one stilbene derivative called
resveratrol have been detected in propolis extracts by
capillary zone electrophoresis.[11] Propolis also contains
important vitamins, such as vitamins B1, B2, B6, C, and E
and useful minerals such as magnesium (Mg), calcium
(Ca), potassium (K), sodium (Na), copper (Cu), zinc
(Zn), manganese (Mn),and iron (Fe). A few enzymes,
such as succinic dehydrogenase, glucose-6-phosphatase,
adenosine triphosphatase, and acid phosphatase, are also
present in propolis.[12]
Chemical structures
Kaempferol, quercetin, galangin, chrysin, pinocembrine,
p-coumaric acid, 3, 5 diprenyl-p-coumaric, saccharin are
some of the chemical structures flavonoids and phenolic.
Fig. 2: Some typical flavonoids and phenolic present
in bee propolis.
Melting Point: Propolis mp 25°C - 45°C, in frozen
condition it becomes hard and brittle. It will become
brittle at higher temperatures. Above 45°C, it will
become increasingly sticky and gummy. Propolis is in
liquid sate at 60°C to 70°C, but the mp may vary
according to sample up to 100°C.
Solubility of Propolis: Propolis is made of variable
chemical constituents. Therefore, it cannot be used
directly. Propolis is extracted commercially with suitable
solvents such as common solvents water, methanol,
ethanol, chloroform, dichloromethane, ether, and
acetone. The most Many of the bactericidal components
are soluble in water or alcohol.[13] India, being a vast
country, has a number of varieties of propolis differing in
chemical compositions and medicinal values which are
mentioned in table 1 but unfortunately it is still to be
explored.
Table. 1: Solvents used for the extraction of several of
propolis with different chemical composition.
Solvents
Water
Methanol
Ethanol
Chloroform
Dichloromethane
Ether
Acetone
Role of Bee Propolis in Bee Hive
Bees use bee propolis for the following uses
o Reinforce the structural stability and provide thermal
insulation to the hive.
o Reduce vibration.
o Make the hive more defensible by narrowing the
existing entrance (in wild colonies) to a single "choke
point".
o Make the hive more defensible by sealing holes: a hive
will have a propolis cache (as much as 1 pound) for
emergency patch jobs.
o Prevent diseases and parasites from entering the hive,
and to inhibit fungal and bacterial growth.
o Mitigate putrefaction within the hive.
Bees usually carry waste out of and away from the hive.
However, if a small lizard or mouse, for example, finds
its way into the hive and dies there, bees may be unable
to carry it out through the hive entrance. In that case,
they would attempt instead to seal the carcass in
Mamillapalli et al. European Journal of Pharmaceutical and Medical Research
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propolis, essentially mummifying it and making it
odorless and harmless.[14]
Biological Activities of Bee Propolis
Antioxidant Activity: Indian bee propolis contains
chemical constituent‘spinocembrin and galangin. The
aqueous extract of propolis (AEP) showedhigher activity
compared to the ethanolic extract of propolis (EEP)
which may be due to highpolyphenolic content. It can be
used in prevention of various free radical related
diseases. Galangin also showed comparable activity with
that of AEP and EEP and highest activity than
pinocembrin.[15]
The free radical scavenging effect of propolis as well as
of vitamin C was studied using 1,1-diphenyl-2-
picrylhydrazyl (DPPH) free radical system. The free
radical scavenging activity of EEP wascomaparable to
standard as ascorbic acid.[13]
Antibacterial Activity
The antimicrobial property of propolis was studied by
agar diffusion method against Staphylococcus aureus,
Bacillus subtilis, Pseudomonas aeruginosa, Escherichia
coli, Candida albicans, and Asparagus nigar. Ethanolic
extracts of sample (Conc. 200 mg/ml) showed high
antibacterial activity than methanolic extracts against
gram-positive, Bacillus subtilis, but least activity against
gram-negative bacteria, P. aeruginosa and E. coli. The
yeast C. albicans showed the moderate zone of inhibition
whereas A. Niger did not show any activity.[13]
Antifungal Activity
Propolis was studied for antifungal activity in various
fruit juices. It inhibited the spoilage of fruit juices due to
the presence of flavonoids.[16] Propolis, the bee duct was
found to show highest antifungal activity with 40 yeast
strains of C. albicans, C. glabrata, C. krusei, and
Trichosporon spp.[17] Propolis inhibited the growth of
Trichosporon spp. (MIC 0.1–0.4 μg/ml), and
Rhodotorula spp. (MIC <0.01 μg/ml). The most sensitive
strain was found to beRhodotorula spp. The most
resistant strain was C. Albicans. Indian propolis was also
found to be more effective anticaries agent against
Streptococcus mutans.[18]
Vaginal Use
To formulate the propolis microparticles (PMs) from
Brazilian propolis and to check activity of the propolis
extract (PE) against clinical yeast C. albicans and 31
non-C. albicans(C. glabrata, C. tropicalis, C.
guilliermondii, and C. parapsilosis) isolates of
importance in the vulvovaginal candidiasis (VVC).
Moreover, the main antifungal drugs used in the
treatment of VVC were also tested. C. albicans isolates
showed resistance or dose-dependent susceptibility for
the azolic drugs and amphotericin B. Non-C. albicans
isolates showed more resistance and dose-dependent
susceptibility for the azolic drugs than C. albicans.[19]
Antiprotozoan activity
Antiprotozoal activity is evaluated by an in vitro growth
inhibitory effect on a culture of parasites after incubation
in the presence of different concentrations of propolis.
The effect of European propolis on protozoa reported by
several publications that cause diseases in humans and
animals such as trichomoniasis, toxoplasmosis,
giardiasis, Chagas disease, leishmaniasis, and malaria.
Indeed, Antiprotozoan activity has also been reported on
Giardia lamblia, Trichomonas vaginalis, Toxoplasma
gondii, Leishmania donovani, and Trypanoso macruzi.[20]
Anti tumoral Activity
The chemopreventive activity of propolis in animal
models and cell cultures was studied. It inhibits DNA
synthesis in tumour cells, induces apoptosis of tumour
cells, and activates macrophages to produce factors
capable of regulating the function of B, T and NK cells,
respectively. Moreover, flavonoids from propolis play a
protective role against the toxicity of the
chemotherapeutic agents or radiation in mice.[21]
Anti-Inflammatory Activity
Inflammation is the complex response of vascular tissues
to harmful stimuli, such as pathogens, damaged cells,
irritants, and free radicals. Anti-inflammatory activity
involves the primary effect of the host defense system.
Propolis has inhibitory effects on myeloperoxidase
activity, NADPH-oxidase ornithine decarboxylase,
tirosine-protein-kinase, and hyaluronidase from guinea
pig mast cells. Bee propolis exhibits anti-inflammatory
activity because of the presence of active flavonoids and
cinnamic acid derivatives such as acacetin, quercetin,
and naringenin,caffeic acid phenyl ester (CAPE) and
caffeic acid (CA).[22] Dietary propolis suppresses the
lipoxygenase pathway of arachidonic acid metabolism
during inflammation in vivo. CAPE was a more potent
modulator of arachidonic acid metabolism than caffeic
acid, quercetin, and naringenin.[23]
4.6 Hepatoprotective Activity
Protective potential of propolis was evaluated against
mercury-induced oxidative stress and antioxidant
enzymatic alteration in mice liver. Exposure to mercuric
chloride (HgC12; 5 mg/kg; i.p.) induced oxidative stress
by increasing lipid peroxidation and oxidized glutathione
level along with concomitant decrease in glutathione and
various antioxidant enzymes. Mercury intoxication
deviated the activity of liver marker enzyme in serum.
Conjoint treatment of propolis (200 mg/kg; p.o.)
inhibited lipid peroxidation and oxidized glutathione
level whereas increased glutathione level.[24]
4.7 Immunomodulatory Action
The immunomodulatory action of a water-soluble
derivative (WSD) of natural propolis was investigated.
The oral and parenteral administration of the WSD
enhanced the survival rate and the mean survival time in
experimental bacterial (Klebsiella pneumoniae,
Staphylococcus aureus) and fungal (Candida albicans)
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infections in mice. An increased resistance was observed
also in Klebsiella pneumoniae infection induced after
cyclophosphamide treatment.[25]
Formulations Used in Propolis Extract
Ethyl cellulose micro particles containing propolis
ethanolic extract (PE) were prepared by the
emulsification and solvent evaporation method. Three
ratios of ethyl cellulose to PE dry residue value (DR)
were tested (1: 0.25, 1: 4, and 1: 10). Moreover,
polysorbate 80 was used as emulsifier in the external
phase (1.0 or 1.5% w/w).
Fig. 3. Marketed tablets and drops formulations.
Regular particle morphology without amorphous and/or
sticking characteristics was achieved only when ethyl
cellulose: DR ratio (1: 0.25) and 1.0% polysorbate 80
were used. Micro particles had a mean diameter of
85.83 μm. These ethylcellulose microparticles containing
propolis would be useful for developing propolis
aqueous dosage forms without the strong and unpleasant
taste, aromatic odour, and high ethanol concentration of
PE.[26] It is available in the form of solid and liquid
dosage forms (Fig. 3).
Therapeutic Applications of Propolis
o Canker sores: Propolis relieves canker sores on oral
administrationdaily for 6-13 months.
o Cold sores: Applying 3% propolis ointment five times
daily helps improve healing time and reduce pain from
cold sores.
o Genital herpes: Applying 3% propolis ointment four
times daily for 10 days improves healing of lesions in
people with genital herpes faster and more completely
when compared to 5% acyclovir ointment.
o A type of intestinal infection called giardiasis:That
taking a 30% propolis extract for 5 days can cure
giardiasis in more people than the drug tinidazole.
o Minor burns: Early research shows that applying
propolis to the skin every 3 days might help treat minor
burns and prevent infections.
o Mouth surgery: Early research shows that using a
propolis mouth rinse five times daily for 1 week might
improve healing and reduce pain and swelling after
mouth surgery.
o Thrush (Oropharyngeal candidiasis): Early research
suggests that using Brazilian green propolis extract four
times daily for 7 days can prevent oral thrush in people
with dentures.
o Upper respiratory tract infections: There is some
early evidence that propolis might help prevent or reduce
the duration of common colds and other upper
respiratory tract infections.
o Vaginal swelling (Vaginitis): Early research suggests
that applying a 5% propolis solution vaginally for 7 days
can reduce symptoms and improve quality of life in
people with vaginal swelling.
o Warts: Early research shows that taking propolis by
mouth daily for up to 3 months cures warts in some
people with plane and common warts. However, propolis
does not seem to treat plantar warts.[27]
o Improving immune response.
o Nose and throat cancer
o Stomach and intestinal disorder
o Tuberculosis
o Ulcers
Special Precautions & Warnings
Propolis is safe by orall administration or external
application. Lozenges prepared by using propolis can
produce irritation and mouth ulcers.
o Pregnancy and breast-feeding: Avoid use.
o Asthma: Avoid using propolis in asthma.
o Allergies: It should not be used in persons who are
allergic to bee by-products such as honey, conifers,
poplars, peru balsam, and salicylates.
o Bleeding conditions:I t increases the risk of bleeding
in people with bleeding disorders. Therefore it should be
avoided before 2 weeks before surgery.[28]
CONCLUSION
Propolis has been used extensively now a days for its
variable chemical components, strong pharmacological
properties and low toxicity than synthetic medicines. The
wide spectrum of therapeutic effects make propolis a
potential therapeutic candidate in several clinical
scenarios. Clinical studies are in progress to verify the
effects of propolis in the prevention and treatment of
diseases.
ACKNOWLEDGEMENT
Authors are thankful to Vijaya Institute of
Pharmaceutical Sciences forWomen, Enikepadu,
Vijayawada for encouragement and support.
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Chapter
Full-text available
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At this Conference we are considering the products of social bees, which beekeepers harvest from them. Candidate bees (Table 1, Figure 1) are: first, all the honey bees: Apis mellifera from Europe, eastern Mediterranean lands and Africa; Apis cerana the hive bee in Asia, and Apis dorsata, Apis florea and related species in the tropics of Asia. Second, in the tropics of all continents there are stingless bees (Meliponinae), some 500 species in all. In addition, honey—but not wax—is produced by colonies of honey wasps (Vespidae) and honey ants (Formicinae) and is harvested from them. The wasps live in parts of tropical South America, and the ants in some dry areas of Australia and North America.
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Propolis, a natural product honeybee, has been used for thousands of years in folk medicine for several purposes. In this work, we have investigated the antimicrobial and antioxidant activity of propolis collected from west zone of India that is, Gujarat. The antimicrobial activity was done by agar diffusion method against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Asparagus niger. Ethanolic extracts of sample showed high antibacterial activity against Gram-positive (B. subtilis) but least activity against Gram-negative bacteria (P. aeruginosa and E. coli). The yeast C. albicans showed the moderate zone of inhibition where as A. niger did not show any activity. Pet. ether and chloroform extracts did not show any activity. The maximum zone of inhibition of the ethanolic extracts of propolis (EEP) was found against the B. subtilis at the conc. 200 mg/ml where as the least was in the 40% methanolic extracts. The free radical scavenging effect of propolis as well as of vitamin C in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical system was determined. The free radical scavenging activity of EEP was 70.96% and 72.97% respectively in the concentration range of 100 mcg at the difference of 30 min and 1hr respectively. The result of free radical scavenging effect of vitamin C was 94.7% at 100 mcg and 93.4% at 10 mcg. The methanolic extracts showed the least free radical scavenging when compared to the 40% methanolic and ethanolic extract of the propolis.
Article
Melanoma the more dangerous skin cancer and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We have investigated the ability of an ethanolic extract of Algerian Propolis (EEP) to control melanoma tumour growth when given as either preventive or therapeutic to mice bearing B16F1melanoma tumour. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (–75%), further confirmed by measuring the Mitotic Index (–75%) and Ki-67 (–50%) expression. EEP given before or before and after tumour occurrence also reduced tumour growth, but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40%, respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced melanoma cell proliferation and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and extended mice life span. This complementary therapy to classical treatment may help patients with melanoma, when used under certain conditions for which autophagy is not contraindicated.
Article
Ethylcellulose microparticles containing propolis ethanolic extract (PE) were prepared by the emulsification and solvent evaporation method. Three ratios of ethylcellulose to PE dry residue value (DR) were tested (1:0.25,1:4 and 1:10). Moreover, polysorbate 80 was used as emulsifier in the external phase (1.0 or 1.5% w/w). Regular particle morphology without amorphous and/or sticking characteristics was achieved only when an ethy!cellulose:DR ratio of 1:0.25 and 1.0% polysorbate 80 were used. Microparticles had a mean diameter of 85.83 urn. The entrapment efficiency for propolis of the microparticles was 62.99 ± 0.52%. These ethylcellulose microparticles containing propolis would be useful for developing propolis aqueous dosage forms without the strong and unpleasant taste, aromatic odour and high ethanol concentration of PE.
Article
Since primeval times, the inflammatory process has been described in many different ways. Several anti-inflammatory therapies have been used in different biological models. However, in a recent "back to nature move", modern man is searching for natural products with medicinal properties, particularly those obtained from plants and bees. Propolis has been used in folk medicine for a very long time. The many compounds present in propolis require investigation.Physical-chemical analysis studies have not sufficiently established quality standards of propolis containing products. These standards should depend especially on their different pharmacological activities. There are few studies reporting on the in vitro anti-inflammatory activity of propolis containing products. It is necessary to evaluate the anti-inflammatory potential of commercial products containing propolis.
Article
We report for the first time the antioxidant activity of the aqueous and ethanol extracts of Indian propolis (AEP and EEP, respectively). The antioxidant activity was measured by chemical and electrochemical assays. Reducing power and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were the chemical assays, whereas, cyclic voltammetry was used as the electrochemical assay. In all these assays, AEP showed significantly greater activity over EEP; which is in contradiction with the previous reports of propolis from other countries. This may be due to its higher polyphenol content. Hence aqueous extract may well be a substitute of organic solvent extracts of propolis. Moreover, two flavonoids, pinocembrin (1) and galangin (2) were isolated from EEP; among which (2) showed high DPPH radical scavenging activity. Thus Indian propolis, being a rich source of natural antioxidants, may be used in the prevention of various free radicals related diseases.