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Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market

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Chapter 4
Functional Properties of Brazilian Propolis: From
Chemical Composition Until the Market
Andresa A. Berretta, Caroline Arruda,
Felipe Galeti Miguel, Nathalia Baptista,
Andresa Piacezzi Nascimento,
Franciane Marquele-Oliveira, Juliana Issa Hori,
Hernane da Silva Barud, Bianca Damaso,
César Ramos, Raul Ferreira and Jairo Kenupp Bastos
Additional information is available at the end of the chapter
Provisional chapter
Functional Properties of Brazilian Propolis: From
Chemical Composition Until the Market
Andresa A. Berretta, Caroline Arruda,
Felipe Galeti Miguel, Nathalia Baptista,
Andresa Piacezzi Nascimento,
Franciane Marquele-Oliveira, Juliana Issa Hori,
Hernane da Silva Barud, Bianca Damaso,
César Ramos, Raul Ferreira and Jairo Kenupp Bastos
Additional information is available at the end of the chapter
Propolis is a product obtained from resins and exudates of dierent plants from
dierent regions in order to protect the comb, with peculiar organoleptic, chemicals
and biological properties. Considering this, this chapter presents the types of Brazilian
propolis as the types available nowadays, their chemical compositions, as well as,
some of their important biological properties enabling employing them as important
health food, such as antimicrobial, antioxidant, and immunomodulation action.
Various in vivo and clinical trial studies, conducted in dierent regions, on the
safety and dosage of propolis, technologies used to obtain propolis extract, and
several innovative presentations of this promising bee product are also presented in
this chapter. Finally, this chapter aims to present the regulatory aairs, potential
market for propolis around the world, and perspectives for a near future.
Keywords: Brazilian propolis, green, red, brown, chemical composition, antimicrobial,
immunomodulatory, antioxidant, extraction process, innovation, regulatory aairs, po‐
tential market
© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (, which permits unrestricted use, distribution,
and reproduction in any medium, provided the original work is properly cited.
© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction and a brief history
The antique civilizations always used bee products as valuable therapeutic resources in their
medicinal practices. The history of medicine of the Assyrian civilizations, Chinese, Tibetan,
Inca, Egyptian, and also the Greco‐Roman is very rich and possess records of centenary
formulations, including propolis to treat or prevent diseases. Old Egyptians, Greeks, and
Romans used propolis to treat wound, cutaneous lesions, ulcers, and chirurgical interventions
In Egypt, propolis was used as one of the main ingredients used in the formulations to embalm
cadavers. It was also used by Aristotle, Dioscorides, Pliny, and Galneo as an antiseptic and
wound‐healing. The Greeks, including Aristotle and Hippocrates, adopted it as an internal
and external healing. Pliny Roman historian refers to propolis as a medicine to reduce swelling
and relieve pain [2].
The term “propolis”, “pro” in favor of and “polis”, “city of bees”, which means in defense of
the honey comb, was described in the sixteenth century in France [3], and in the seventeenth
century, propolis was considered an ocial drug by London Pharmacopoeia [4]. In the sub‐
sequence centuries, propolis has aracted growing interest due to its medical properties, es‐
pecially in Eastern Europe. In 1908, the rst scientic article about propolis chemical
properties and composition [5] was published, indexed on Chemical Abstracts. In 1968, the
abstract of the rst patent was published on Chemical Abstracts [6].
In South Africa, during the war in the end of the nineteenth century, propolis was largely
used because of its healing properties [3] and in the Second World War it was used by sever‐
al Soviet clinicians [2].
In the last decades, propolis has gained wide acceptance as traditional medicine in several
parts of the world. This disseminated interest in propolis in several countries encouraged a
large number of studies considering chemical and biological properties of propolis [7].
Nowadays, in the Brazilian market and in several other countries, it is possible to nd prop‐
olis in dierent presentations, such as liquid or powder extract: in boles, capsules, tablets,
vaporizers, syrups, creams, and among others, aiming to act as an antimicrobial [8–10], anti‐
oxidant [11], immunoregulatory [12–14], anti-inammatory [12, 15, 16], antiviral [17] agent,
besides several other functionss. A very large number of publications endorsing these bio‐
logical benets in in vitro”, in vivo,” and in some clinical trials, is be discussed further in
this chapter.
Thus, this chapter presents recent studies about Brazilian types of propolis such as green, red,
and brown, considering their chemical composition and some biological properties such as
antimicrobial, antioxidant, and immunoregulatory, safety aspects, extraction process, and
technology associated, regulatory aspects, potential market and challenges, as well as tenden‐
cies for a near future.
Superfood and Functional Food - An Overview of Their Processing and Utilization56
2. Chemical composition of Brazilian propolis
Propolis is formed by a complex set of components collected by Apis mellifera from dierent
parts of plant resins (twigs, owers, pollen, buons, and exudates of trees) which are deposited
in the hive with saliva and enzymes of the insect to seal the cracks and maintain the temper‐
ature (Figure 1A) [18].
Figure 1. Presentation of dierent types of Brazilian propolis. (A) Apis mellifera collecting Green propolis from Baccharis
dracunculifolia species, (B) green propolis on the intelligent collector, (C) brown propolis and (D) red propolis. Figures
(A) and (B) were gently donated by César Ramos, Natucentro Company. Figures (C) and (D) were gently donated by
Felipe Galeti Miguel, Apis Flora Company. Both companies are associated with ABEMEL.
It consists of resin (50% of the mixture is composed by avonoids and phenolic acids), wax
(30%), essential oils (10%), pollen (5%), and other organic substances (5%). Among the present
compounds, it can be consisted of hydrocarbons, alcohols, aliphatic and aromatic acids, esters
and its derivatives, aldehydes, ketones, avonoids, fay acids, terpenoids, amino acids, sugars,
lignans, vitamins, minerals, etc. [19].
The chemical composition of propolis diers signicantly according to the geographic region
where resins were collected due to the ora of each region, allowing the selection of dierent
plants as source of resin [20].
When this product is derived from Europe or China, for example, the main plant metabolites
found are avonoids and phenolic acids, unlike the stemmed ones from southeastern Brazil,
which, besides phenolic compounds, contain high amounts of terpenoids and prenylated
derivatives of p‐coumaric acid [21]. This dierence in composition reveals the collection of
resinous material, in temperate zones, from poplar, especially species of Populus and in
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
southeastern Brazil, especially from Baccharis dracunculifolia DC (Compositae), popularly
known as “vassourinha do campo” [22].
Regarding Brazilian propolis, it was further divided into 12 classes according to Park et al.
[23]: the rst ve ones originate from the south and have the colors yellow, light brown, dark
brown, light brown, and greenish brown, respectively. Regarding propolis found in the
Northeast, it was divided into six groups such as reddish brown, greenish brown, dark brown,
yellow, dark yellow, and yellow. Finally, the last of these classes regards the kind of propolis
that comes from the Southeast and is known to have a greenish brown or green color and so‐
called green propolis (Figure 1B) [23]. After 2007, the 13 types of propolis was added: this
new kind comes from the mangroves of the Brazilian states of Sergipe, Alagoas, Paraiba,
Pernambuco, and Bahia. Among the Brazilian propolis, the green, the brown (Figure 1C), and
the red (Figure 1D) ones are the most studied and relevant to the Brazilian economy due to
their biological activities and exports to other countries, such as Japan [24].
2.1. Green propolis
Green propolis is composed of large amounts of phenolic compounds such as artepillin C,
baccharin, kaempferide, isosakuranetin, dihydrokaempferide, drupanin, p‐couma ric acid,
caeic acid, aromadendrin, caeoylquinic acid derivatives, and other compounds, such as the
triterpene lupeol‐3‐(3ʹR‐hydroxy)‐hexadecanoate. The key source of these compounds is B.
dracunculifolia [12, 25–30] (Figure 2).
Figure 2. Chemical structures of compounds found in Brazilian green propolis.
Superfood and Functional Food - An Overview of Their Processing and Utilization58
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
2.2. Red propolis
Many of chemical compounds of red propolis, as well as green propolis, have been determined.
Some of them are elemicin, isoelemicin, methyl isoeugenol, formononetin, biochanin A,
isoliquiritigenin, liquiritigenin, medicarpin, homopterocarpan, quercetin, and vestitol. In the
lipophilic extract, the majority of the compounds found are polyprenylated benzophenones—
guiferone E, xanthochymol, and oblongifolin A (Figure 5). Because the isoavones— 7
formononetin, biochanin A, pinocembrin, and medicarpin—are abundant in red propolis, they
are used as chemical markers for identifying red propolis (Figure 4) [33, 34].
Figure 5. Chemical structures of some compounds found in Brazilian red propolis.
In addition to these compounds, De Mendonça et al. [33] identied caeic acid, ferulic acid,
umbellic acid, p‐coumaric acid, genistein, kaempferol, cathechin, dalbergioidin, epicatechin,
daidzein, 2’‐hydroxyformononetin, evernic acid, naringenin, calycosin, (7S)‐dalbergiphenol,
thevetiaavone, cycloartenol, guiferone C, and other compounds, using LC‐Orbitrap‐FTMS,
a powerful tool to detect compounds because it does not require chromophores such as ultra‐
violet detector and it can detect very low amounts.
Superfood and Functional Food - An Overview of Their Processing and Utilization60
Red propolis has these chemical constituents, mainly due to the collection of resin from
Dalbergia ecastophyllum by the bees. Its red color is due to the presence of cationic C30 isoavans,
retusapurpurins A and B (Figure 6). This is characteristic of the propolis found in Brazilian
Northeast, found especially in hives nearby mangroves in the states of Sergipe, Bahia, Alagoas,
Paraiba, and Pernambuco. This bee product has aracted wide interest because of its numerous
biological activities, such as cytotoxic against several cancer cell lines, antibacterial, antifungal,
anti‐cariogenic, antioxidant, antiproliferative, anti-inammatory, and others [24, 33, 34]. In
addition to its extracts, numerous biological activities of the isolated compounds have been
described [24].
Figure 6. Chemical structures of isoavans, retusapurpurins A and B.
Righi et al. [35], besides the compounds already described, found alkanes such as n‐tricosane,
n‐pentacosane, n‐heptacosane, n‐nonacosane, n‐hentriacontane, and n‐tritiacontane in the
apolar red propolis extract (hexane extract). They also identied other compounds as β‐amirin,
α‐amirin, lupeol, methylguaiacol, trans‐anethole, resorcinol, anisylacetone, cis‐asarone,
farnesol, and among others.
Nunes et al. [36] determined 34 volatile (Table 1) compounds in Brazilian red propolis
and found that the major ones are trans‐anethole, α‐copaene, and methyl‐cis‐isoeugenol
(Figure 7). They found that the chemical composition remains relatively constant during
the year, considering that 17 out of the 34 compounds were detected every season of the
year. But, the compounds δ‐cardinol, ß‐gurjunene, isocaryophyllene, and δ‐cadinene were
found only in the sample collected in October and the alkanes, the 1,8 cineol, and α‐selinene
in the sample collected in July. This can be explained by the visitation of bees, in rainy
seasons of shrubs and in dry seasons of woody plants: when the apiculture pasture changes,
the chemical composition of propolis also changes. Similarly, as trans‐anethole, the other
red propolis compounds show biological activities such as analgesic, anesthesic, antigeno‐
toxic, and antioxidant, making the volatile fraction pharmacologically interesting.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
Class of the compound Compound Class of the compound Compound
Monoterpene p‐Cymene Sesquiterpene α‐Cubebene
Limonene α‐Copaene
1,8‐Cineole β‐Gurjunene
Linalool β‐Caryophyllene
Aromatic compound Naphthalene α‐Bergamotene
Alcohol, aldehyde or ketone 4‐Hydroxy‐4‐methyl‐heptan‐2‐one Farnesene
6‐Methyl‐5‐hepten‐2‐ona €‐β‐Farnesene
Phenylpropanoid Octanal D‐Germacrene
Nonanal α‐Selinene
n‐Decanal Isocaryophyllene
Anisaldehyde β‐Bisabolene
n-Dodecanal δ‐Cadinene
trans‐metil isoeugenol Cadinene
Estragole δ‐Cadinol
Trans‐anethole Aliphatic hydrocarbon Tetradecano
Methyl‐cis-isoeugenol Pentadecano
Elemicin Hexadecano
Table 1. Compounds found in Brazilian red propolis.
Figure 7. Some volatile compounds from Brazilian red propolis.
Superfood and Functional Food - An Overview of Their Processing and Utilization62
2.3. Brown propolis
The brown color is characteristic of propolis from dierent areas, but regarding Brazilian
brown propolis, it is usually referred as the one that comes from the south of the country.
Although many chemical compounds present in this product and their biological eects have
already been identied, this type of propolis has not been well studied as red and green
Brazilian propolis and many scientic reports on brown propolis are relatively old. Its
botanical source seems to be mostly Araucaria, although some compounds found on it are also
present in B. dracunculifolia [37].
Figure 8. Chemical compounds of brown propolis.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
The main compounds identied were: coniferaldehyde, 2,2‐dimethyl‐6‐carboxyethenyl‐2h‐1‐
benzopyran, drupanin, pinocembrin, dicaeoylquinic acid, and artepillin C, isocupressic acid,
acetylisocupressic acid, imbricatoloic acid and a mixture of cis and trans isomers of communic
acid [38–40] (Figure 8).
Among the numerous biological eects reported for brown propolis and its isolated com‐
pounds, it has been observed that both brown propolis and some of its isolated compounds
have antimicrobial eect. In addition, it was possible to determine which compounds are
responsible for such activity, highlighting the importance of chemically know product widely
used by population [38, 41]. Moreover, brown propolis, as well as green propolis, has a
signicant preventive eect against oxidative stress in skin [42].
Brown propolis collected in Mato Grosso do Sul due to the signicant amount of phenolic
compounds in ethanol extract shows high antioxidant and antigenotoxic activities. Its volatile
fraction is composed mainly of the sesquiterpenes spathulenol and (E)‐nerolidol (Figure 3),
which show an antimicrobial eect against Cryptococcus neoformans, Enterococcus faecalis, and
Staphylococcus aureus. They were not mutagenic, considering that the antimicrobial activity is
not because of DNA damage induction [43, 44]. The brown propolis collected from Mato
Grosso also showed antimicrobial activity [45].
Therefore, considering that Brazil has a unique ora, among all types of Brazilian propolis
three types of propolis are highly noticeable: green, red, and brown propolis due to their
singular chemical composition, leading to their biological eects, culminating in the high value
in the international market of Brazilian bee products.
3. Biological properties
3.1. Antimicrobial activity
Antimicrobial properties of Brazilian propolis are well‐documented, including the antibacte‐
rial, antifungal, and antiviral activities. The biological activities of propolis are related to its
chemical composition that varies with the collection period of the resin and the ora of the
region visited by bees [46]. Therefore, in Brazil there are dierent types of propolis, since the
dierent geographical regions of the country have a diversity of plant species. The most
popular types of Brazilian propolis are green and red propolis.
Brazilian green propolis, whose most important plant source is B. dracunculifolia, has been
extensively studied. Several studies have shown the activity of green propolis against several
pathogenic bacteria, including Gram‐positive bacteria (S. aureus, Staphylococcus epidermidis,
Streptococcus pneumoniae, and Kocuria rhizophila) and Gram‐negative bacteria (Haemophilus
inuenzae, Porphyromonas gingivalis, Porphyromonas endodontalis, and Prevotella denticola) [9, 10,
46–48]. The last three bacteria cause periodontal diseases, which aect the periodontal tissues
(tooth supporting tissues). Furthermore, green propolis is active against cariogenic bacteria,
such as Streptococcus mutans, Streptococcus sobrinus, Streptococcus salivarius, Streptococcus
sanguinis, and Lactobacillus casei [48, 49]. However, some Gram‐negative bacteria are not
Superfood and Functional Food - An Overview of Their Processing and Utilization64
susceptible to green propolis, such as Escherichia coli and Pseudomonas aeruginosa [9, 10, 46]. E.
coli can cause urinary tract infections and gastroenteritis, among others, while P. aeruginosa is
associated with nosocomial infections, since it is an opportunistic bacterium.
Antifungal activity of green propolis has been reported against all three morphotypes of
Candida albicans (yeast, pseudohyphae, and hyphae) [50]. At the cellular level, green propolis
is able to induce apoptosis and secondary necrosis in yeasts, as showed in a study using
Saccharomyces cerevisiae as a model organism [51]. Green propolis is also active against
lamentous fungi (molds), such as Trichophyton rubrum, Trichophyton tonsurans, and Trichophy-
ton mentagrophytes [52], which cause dermatophytosis. Ngatu et al. [53] reported the antimy‐
cotic eect of green propolis in patients with tinea pedis interdigitalis and tinea corporis
caused by T. rubrum.
Green propolis also has the capacity to inhibit virus propagation. Shimizu et al. [54] reported
that the ethanol extract of green propolis exhibited moderate ecacy in limiting herpetic skin
lesions in mice infected with herpes simplex virus type 1 (HSV‐1). Urushisaki et al. [17] showed
the anti-inuenza eect (H1N1 inuenza virus) of the water extract of green propolis and its
caeoylquinic acids, which may have a cytoprotective action by aecting the internal cellular
process. Takemura et al. [55] also reported the anti-inuenza eect of the water and ethanol
extracts of green propolis and their 3,4-dicaeoylquinic acid, which enhance viral clearance
by increasing tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) in the lungs of
mice infected with H1N1 inuenza virus.
Batch‐to‐batch variability is a common problem in the manufacture of propolis extracts. Since
medicinal use of these extracts must rely on appropriate quality requisites, batch‐to‐batch
reproducibility is essential to ensure consistent quality. Therefore, Berrea et al. [8] developed
the propolis standardized extract (EPP‐AF®), an ethanolic extract which contains green
propolis and has batch‐to‐batch chemical reproducibility. Furthermore, it has several biological
activities, including antibacterial and wound‐healing activities [8]. Figure 9 shows some results
obtained by our research group, showing the antibacterial activity of EPP‐AF® and extracts
of brown, red and green propolis.
Figure 9. Zones of inhibition (disk diusion method) provided by 1: Extract of brown propolis from the south of Brazil;
2: Extract of red propolis from the northeast of Brazil; 3: Extract of green propolis from the southeast of Brazil; 4: Prop‐
olis standardized extract (EPP‐AF®); (a): Staphylococcus aureus ATCC 25923; (b): Streptococcus neumonia ATCC
49619; (c): Klebsiella neumonia ATCC 10031.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
Our research group also has developed and evaluated dierent pharmaceutical forms of green
propolis extracts, including propolis ethanolic extract (PEE), propolis water extract (PWE),
propolis soluble dry extract (PSDE), and propolis matricial microparticles (PMM). With respect
to antifungal activity (S. cerevisiae and C. albicans), PEE was the most potent followed by PWE,
PMM, and PSDE [50]. The same results were obtained against Lactobacillus species (Gram‐
positive bacteria) (data not published yet).
Brazilian red propolis, in its turn, is produced from resinous exudates of D. ecastophyllum,
found mainly in Northeastern Brazil (states of Alagoas, Bahia, Paraíba, Pernambuco, and
Sergipe) [56]. Ethanolic extracts of red propolis showed activity against Gram‐positive
bacteria (S. aureus and Bacillus subtilis) and Gram‐negative bacteria (E. coli and P. aeruginosa)
[56–58]. These results are very interesting, since green propolis is not active against E. coli and
P. aeruginosa [9, 10, 46]. Red propolis also has antifungal activity. Siqueira et al. [52] reported
its activity against some dermatophytes (T. rubrum, T. tonsurans, and T. mentagrophytes).
Isoavone formononetin is one of main chemical compounds in red propolis. Das Neves et al.
[59] evaluated the activity of this compound against some bacteria (S. aureus, S. epidermidis,
and P. aeruginosa) and yeasts (C. albicans, Candida tropicalis, and C. neoformans). The MIC value
was 200 μg/ml for all bacteria and 25 μg/ml for the yeasts [59]. (6aS,11aS)‐Medicarpin is the
other chemical compound in red propolis, which exhibits a strong antibacterial activity, since
MIC values of 16, 32 and 32 μg/ml were obtained against S. aureus, B. subtilis, and P. aerugino-
sa, respectively [57].
Kamuyama et al. [60] evaluated the use of green propolis to control microorganisms in
minimally processed carrot. The study involved the comparison between: (i) carrot sanitation
with 200 mg/l of total available chlorine, (ii) chlorinated solution “A” together with edible lm
with 0.4% propolis solution, and (iii) carrot sanitation with 0.4% propolis solution, prepared
from 25% propolis alcoholic extract. Mesophilic and psychrotrophic aerobic bacteria, mold,
and yeast were counted during the storage of samples of processed carrots at 10°C. The results
demonstrated that the results for all treatments were similar to mesophilic and psychrotrophic
bacteria. For mold and yeast count, the application of treatments (ii) and (iii), in the end of
study, was similar to T0, suggesting that the use of propolis as a food preservative is viable
and promising.
Borges et al. [61] evaluated the antibacterial and antifungal properties of dierent concentra‐
tions of a propolis hydroalcoholic extract in fresh pork sausage. This product is target of
microbiological contamination, with consequent commitment of “shelf‐life” and ability to
cause diseases, factors that stimulate food companies to use synthetic preservatives as sodium
nitrate, which possess high toxicity.
Interestingly, the results demonstrated that propolis extract (0.03 g/100 g of food) used showed
greater antibacterial and antifungal results when compared to sodium nitrate.
3.2. Antioxidant activity
The propolis antioxidant property is one of the most studied biological activities worldwide.
This biological property presents outstanding importance in the general benets that propolis
Superfood and Functional Food - An Overview of Their Processing and Utilization66
may bring to human health as the free‐radical scavenging capacity of propolis compounds
may be closely related to the anti-inammatory, antimicrobial, anticancer activities, as well as,
prevention of atherosclerosis, skin damages, ageing, and among others.
Several antioxidant methods are available to study propolis, i.e., the DPPH assay, scavenging
of hydroxyl radical by the deoxyribose assay, inhibition of lipid peroxidation, inhibition of
chemiluminescence produced in the H2O2/luminol/horseradish peroxide (HRP) system and
inhibition of chemiluminescence produced in the xanthine/luminol/xanthine oxidase (XOD)
system, and among others.
Propolis origin Antioxidant activity/method Reference
Brazil (marketed‐standardized
extract—PI 0405483‐0)
0.016 μl/ml (IC50) inhibition of lipid peroxidation
0.22 μl/ml (IC50) inhibition of chemiluminescence produced in the H2O2/
luminol/horseradish peroxide (HRP) system
0.005 μl/ml (IC50) inhibition of chemiluminescence produced in the xanthine/
luminol/xanthine oxidase (XOD) system
0.024 μl/ml (IC50) scavenging of hydroxyl radical by the deoxyribose assay
Campo grande Brazil (raw‐
material*propolis from
stingless bees)
3 μg/ml (IC50) scavenging of DPPH
No hemolyis—oxidative hemolysis inhibition assay
50–125 μg/ml—eciency in inhibiting of AAPH‐induced lipid peroxidation
Nan Province innorthern
Thailand (raw‐material)
Not indicated ‐ scavenging of DPPH
Observation: the authors inform the higher the ethanol amount in the
ethanol aqueous solution, the higher the antioxidant activity
Alagoas, Brazil (brown
8.01 μg/ml (IC50) scavenging of DPPH—ethanolic extract [33]
Mediterranean propolis Most prepared extracts inhibited lipid oxidation—oxidation of sunower oil
Brazil aqueus extract 0.62 μg/ml (IC50)—inhibition of lipid peroxidation employing brain
Table 2. Antioxidant activity of propolis from several regions in the world.
Some of these methods mimic the physiological conditions found in human body, this is the
case of lipid peroxidation assay, in which membrane fractions (from mitochondria or brain)
are used. In this method, the addition of iron salts triggers the decomposition of lipid peroxides
into peroxyl (LOO•) and alkoxyl (LO•) radicals that can abstract hydrogen from polyunsa‐
turated acyl chains and propagate lipid peroxidation. Any antioxidant capable of scavenging
LOO• and LO• will decrease peroxidation. However, other methods can be considered more
accessible, such as DPPH, which can easily demonstrate, in large scale, the antioxidant capacity
of propolis samples from dierent sources or dierent batches. According to Marquele‐
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
Oliveira et al. [62], this method could even be employed as an alternative for worldwide
characterization and standardization of natural products. A good correlation of the DPPH
method was observed against lipid peroxidation assay. This assay is based on the ability of
DPPH, a stable free radical, to be quenched and thereby decolorize in the presence of antiox‐
idants resulting in a reduction in absorbance values. In the DPPH test, the antioxidants reduce
the DPPH radical to a yellow‐colored compound, diphenylpicrylhydrazine. The extension of
the reaction will depend on the hydrogen‐donating ability of the antioxidants [63].
Propolis antioxidant properties have been fully investigated and both propolis raw material
and propolis commercial extracts have been studied. Table 2 shows examples of the antioxi‐
dant prole and the method employed for each sample, focusing on their collecting origin.
Phenolic compounds have been reported as the main propolis compounds responsible for the
antioxidant property. The antioxidant role of polyphenols results from the donation of
hydrogen atoms from an aromatic hydroxyl group to the free radical, leading to stabilization
of the radical [64]. During the evaluation of propolis fractions (from Brazil), Wang et al. [65]
observed a strong inhibition of lipid peroxidation using rat liver homogenate at a concentration
of 2 mg/ml, and this activity was related to the presence of avonoids. However, it is known
that other than phenolic compounds, avonoids are involved in the antioxidant activity of
propolis. So a series of phenolic compounds, including avonoids, were assessed against the
peroxidation of linoleic acid in a micellar solution. The results demonstrated that polyphenols
in general present higher activity than BHT (butylated hydroxytoluene), a well‐known
antioxidant [66]. In a study using cell culture, artepillin C has been proposed as a strong
candidate to be responsible for the antilipoperoxidative activity of Brazilian propolis [67].
Santos et al. [68] assessed the antioxidant activity of avonoids and reported that the presence
of structural groups, i.e., the B ring dihydroxyl, double bond in C2 and C3 in conjunction with
the 4‐oxo function, and the additional presence of hydroxyl groups in C3 and C5 (except for
quercetin and 3ʹ‐O‐methyl‐quercetin), were the most potent inhibitors of lipid peroxidation
using mitochondria. This antioxidant activity was also due to Fe chelation, which may explain
the activity of avonoids and polyphenols which do not have the above described structural
groups [69].
After screening the antioxidant properties of propolis around the world, not only in the
presented references, but also in the vast literature about this topic, one can observe a wide
variation of responses. On the one hand, the antioxidant ability of each extract is related to the
type and amount of phenolic compounds present in each extract, closely dependent on the
propolis origin. But, on the other hand, no standardization regarding the solid soluble amount
in each sample is presented, making comparisons among them not adequate. However, the
presence of antioxidant activity in every propolis source studied is clearly observed and this
activity has special importance to propolis biological properties.
Tian et al. [73] have shown that ethanolic propolis extract (EPE) protects endothelial cells from
oxidized low‐density lipoprotein (ox‐LDL)‐induced apoptosis and inhibits atherosclerotic
lesion development. This research group has also demonstrated the eect of propolis extract
on endoplasmic reticulum stress‐C/EBP homologous protein pathway‐mediated apoptosis.
Apoptosis, especially in macrophages present in atherosclerotic lesions, is considered as a
Superfood and Functional Food - An Overview of Their Processing and Utilization68
prominent feature of advanced atherosclerotic plaques, suggesting that macrophage apoptosis
is closely related to the atherosclerotic development and subsequent plaque rupture, which is
the prominent event that results in the majority of clinical manifestations of acute coronary
syndrome such as acute myocardial infarction and sudden coronary death [74]. Thus, pro‐
tecting macrophages from apoptosis is believed as an eective approach to aenuate plaque
instability and combat acute vascular events.
Additional studies investigated the potential use of topically and orally administered
propolis extracts to prevent UV irradiation‐induced oxidative stress in skin. Brazilian
propolis extracts both green and brown successfully prevent UV‐induced GSH (endogenous
antioxidant) depletion in vivo and are both promising antioxidant systems against oxidative
stress in skin [75].
Propolis also due to its antioxidant properties was tested against acute lung inammation
(ALI) caused by cigaree smoke (CS) in vivo. The researchers observed that propolis (P)
treatment (200 mg/kg) normalized all biochemical parameters in the CS+P group compared
with the CS group, including nitrite, myeloperoxidase level, antioxidant enzyme activities
(superoxide dismutase, catalase and glutathione peroxidase), reduced glutathione/oxidized
glutathione ratio, and malondialdehyde. Additionally, TNF‐α expression reduced in the CS+P
group when compared with the CS group. They suggested, therefore, the potential antioxidant
and anti-inammatory role for propolis with regard to ALI caused by CS in mice [76].
Regarding the inuence of the propolis antioxidant activity in food preservation, when
combined with heat treatment in apple juice, propolis (0.1 mg/ml) reduced the thermal
treatment time and temperature needed to inactivate 5 log10 cycles of E. coli. No inuence on
organoleptic properties of the apple juice, which implies the possibility of obtaining a senso‐
rially appealing, low‐pasteurized apple juice with the functional properties provided by
propolis was reached [77]. In another study, Costa et al. [78] studied the bifunctional biobased
packing containing red propolis. In addition to the antimicrobial eect on coagulase‐positive
Staphylococci in cheese curds, the authors observed the reduced oxidation of buer during
storage due to the antioxidant properties of propolis.
3.3. Immunoregulator
One of the biological eects of propolis is its immunomodulatory eect—by either enhancing
or suppressing the immune system. This contradictory eect is probably due to its complex
chemical variety, the presence in dierent geographic regions, and the dierent forms of
Lile was known about the biological role of propolis until the 1990s, but recently numerous
studies have been published, providing an important contribution to this research eld.
Immunomodulatory as well as anti-inammatory eects of propolis have been widely
demonstrated both in vitro and in vivo [15, 79–82].
These eects are mainly related to its constituents, especially the phenolic compounds,
including avonoids as major components. Among the main types of avonoids contained in
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
propolis are: pinocebrin, chrisin, and caeic acid phenethyl ester (CAPE). In addition to
avonoids, propolis can also contain cinnamic acid derivatives such as caeic acid and its
esters, besides sesquiterpenes, quinones, and coumarins [83–85]. The typical constituents of
Brazilian propolis, especially the Brazilian green propolis, are: caeoylquinic acid and
prenylated derivatives of cinnamic acid, such as artepillin C, p‐coumaric acid, baccharin, and
drupanin [23, 86, 87].
Despite the intensive search for the main constituent of propolis responsible for its immuno‐
modulatory role, its eect seems to be associated with a combination of its dierent compo‐
nents [88].
Bachiega et al. [89] evaluated the propolis extract and its phenolic compounds, such as
cinnamic and coumaric acids on cytokine production (IL‐1b, IL‐6, and IL‐10) before or after
macrophage challenge with LPS, to assess a possible immunomodulatory action. They
observed a signicant reduction in IL‐6 and IL‐10 in macrophages treated with the compounds
only when the LPS was added before the stimulus, whereas the propolis extract was capable
to inhibit the cytokine production both before and after the LPS addition. Thus, concluding
that this eciency could have occurred due to the synergistic eect of all compounds present
in the extract [89]. On the other hand, the eect of polyphenolic compounds isolated from
propolis and propolis extract was investigated on the growth and metastatic potential of a
transplantable mammary carcinoma of CBA mouse. The results indicated that water‐soluble
extract of propolis (WSDP), caeic acid (CA), quercetin (QU), and CAPE could be useful tools
in the control of tumor growth in experimental tumor models [13].
The immunomodulatory activity of propolis extract was also investigated in vivo using the
ovalbumin (OVA)‐induced asthma model. Sy et al. [90] demonstrated that propolis extracts
can suppress the serum levels of OVA-specic antibody IgE and IgG1 and aenuate the airway
inammation in treated mice, probably by the ability of propolis to modulate cytokine
production. These ndings suggest that propolis extracts may be a potential novel therapeutic
agent for asthma [90].
Park et al. [91] evaluated another ethanolic extract of propolis (EEP) from Korea in an
inammatory animal model of hind paw edema induced by carrageenan. They observed a
signicant inhibition of the development of paw edema and increased vascular permeability
coupled with an excellent analgesic eect in treated animals. They also showed a signicant
inhibitory eect on granuloma and exudate formation. The authors suggested that the anti-
inammatory eects of propolis observed might be due to its inhibitory eect on prostaglandin
production [91].
In fact, Mirzoeva et al. [92] demonstrated the eect of another ethanolic extract of propolis in
suppressing the prostaglandin and leukotriene generation by murine peritoneal macrophages
in vitro and during zymosan‐induced acute peritoneal inammation in vivo. Furthermore, the
authors described the caeic acid phenethyl ester (CAPE) as being the most potent modulator
of the arachidonic acid cascade among the propolis components examined [92].
Similarly, Borrelli et al. [93] investigated two ethanolic propolis extracts (EPE): with and
without the caeic acid phenethyl ester (CAPE) for their anti-inammatory activity in rats
Superfood and Functional Food - An Overview of Their Processing and Utilization70
using carrageenan foot edema and carrageenan pleurisy models. They observed that only EPE
with CAPE and CAPE alone signicantly inhibited the carrageenan edema in the rat paw and
the number of leukocytes in the pleural exudate in rats, suggesting that the anti-inammatory
activity of propolis is due to CAPE [93].
It is important to say that, despite Brazilian green propolis does not present CAPE in its
composition, it presents a wide range of studies describing its benecial properties such as
antiulcerogenic, anti-inammatory, antimutagenic, antifungal, angiogenesis, antioxidant, and
immunomodulatory [14, 94–98]. Dierent from most European propolis extracts, which
present avonoids as the major component responsible for their eects, the biological activities
of Brazilian green propolis are due to its high levels of phenolic acids such as artepillin C [99].
Studies with Brazilian green propolis have showed its role in inhibiting the development of
pulmonary cancers [100], an antiviral activity in vivo [101], anticancer [102], an anti-inam-
matory activity in vivo and in vitro [12, 16, 87], an antioxidant function in patients with type 2
diabetes mellitus [101, 102], antiherpetic activity [103], and among others [104, 105].
Despite several and growing studies involving the biological eects of Brazilian propolis, the
detailed molecular and cellular basis of the action of propolis on immune cells is still unknown.
The administration of green propolis in animals subjected to chronic stress increased the
generation of hydrogen peroxide, suggesting a modulation in the macrophage activation [106].
Machado et al. [12] veried an immunomodulatory eect of Brazilian green propolis extracts
in acute and chronic inammation models in vivo where the treated animals showed a decrease
production of proinammatory cytokines such as TNF‐α and IL‐6 and an increase in the IL‐10
and TGF‐b anti-inammatory cytokines [12].
Most of the studies reported to date are associated with the immunomodulatory eect
presented by propolis extracts with the modulation of the transcription factor NFkB [107–110].
Recently, it has been demonstrated that Brazilian green propolis can also act in a new
inammatory pathway named inammasome. The inammasomes are a large molecular
platform formed in the cell cytosol in response to stress signals, toxins, and microbial infec‐
tions. Once activated, the inammasome induces the molecule caspase‐1, which in turn
provokes the processing of inammatory cytokines IL‐1β and IL‐18. The Brazilian green
propolis analyzed in this study (EPP‐AF®) was capable of inhibiting the NLRP3 inammasome
and hence signicantly reduces the IL‐1β secretion in mouse macrophages. Thus, indicating
that Brazilian green propolis EPP‐AF® extract has a signicant role in regulating the inam-
masomes [15].
In conclusion, the immunomodulation caused by propolis has been amply demonstrated in
recent years, both in the stimulation and suppression of the immune system, making it
potentially applicable as an alternative adjuvant therapy or even in the treatment of various
Table 3 presents a summary of the activities presented in Section 3.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
Kind of propolis Biological properties References
Brown Antigenotoxicity [43, 44]
Antimicrobial [38, 41, 44, 45]
Antioxidant [42, 75]
Green Antibacterial [8–10, 46, 47, 49]
Anticancer [102]
Antifungal [51–53]
Anti-inammatory [12, 15, 16, 87]
Antimutagenic, [96]
Antioxidant [27, 42, 75, 76, 103]
Antiulcerogenic [94]
Antiviral [17, 54, 55]
Immunomodulatory [12, 88]
Inhibition of angiogenesis [98]
Preservative [60]
Red Antibacterial [24, 56–59]
Anticancer [33]
Anticariogenic [24]
Antifungal [24, 52, 59]
Anti-inammatory [24, 80]
Antioxidant [24, 33]
Antiproliferative [24]
Immunomodulatory [24]
Table 3. Biological activities presented in Section 3—summary.
4. Safety aspects
4.1. Nonclinical studies
Although propolis has been used for centuries around the world demonstrating to be safe,
several scientic studies have been done in order to evaluate propolis safety by oral or topical
route. Here we intend to present Brazilian propolis studies done in animals and, the studies
found in humans, as clinical trials are not so numerous, despite the clinical trials did not focus
on safety, we are presenting them in order to compare the dosages previously used and
documented in humans.
Sforcin et al. [111] evaluated some biochemical parameters of animals treated with several
dierent types of propolis aiming to study propolis safety and the dierences in the propolis
source could interfere in the results. The authors determined total proteins, glucose, urea,
Superfood and Functional Food - An Overview of Their Processing and Utilization72
creatinine, triglycerides, cholesterol, cholesterol‐HDL, aminotransferases, and lactic dehydro‐
genase (LDH). The results demonstrated that all parameters were under standard values for
the species studied and the propolis sources did not aect the results.
Reis et al. [95] evaluated the safety of propolis standardized extract (EPP‐AF®), a Brazilian
propolis composition that presents more than 50% of green propolis, by oral route in mice, in
an acute model. DL50 was determined to be 3000 mg/kg after 24 h of treatment, and dosages
under this value did not demonstrate intoxication signs in the animals. In the subchronic
protocol (30 days) done in Wistar rats, there were no dierences in the food and water intake,
animals’ weight and diuresis. Hematological and biochemical analysis did not show statistical
dierences between the treated (propolis 650 mg/kg) and placebo group. All parameters were
in accordance with reference standards for the species studied. Microscopic analysis of all
tissues did not show any dierences with the placebo group, and it was not possible to detect
any lesions, hemorrhages or cells inltration, demonstrating the safety of oral administration
of Brazilian propolis up to 650 mg/kg during 30 days of ingestion.
Mani et al. [112] evaluated the safety of Brazilian propolis in distinct treatments: (i) rats treated
with 1, 3, and 6 mg/kg/day during 30 days; (ii) rats treated with 1 mg/kg/day of propolis
alcoholic or aqueous during 30 days, and (iii) rats treated with 1 mg/kg/day during 90 and 150
days, demonstrating that all levels of seric cholesterol, HDL‐cholesterol, total lipids, triglycer‐
ides, aminotransferases (AST), and lactic dehydrogenase (LDH) of propolis treated group were
similar to the control group. The authors suggested that Brazilian propolis in the dosages used
during the period of treatment were safe (Table 4).
Type of study (oral route) Dosage Propolis source Species  Dosage converted to
human according FDA
guideline (mg/day)*
Biochemical parameters, 150 days [112] 1, 3 and 6 mg/kg Brazilian Rats 67.74
Biochemical parameters, 60 days [113] 2000 mg/kg Iranian Rats 22,580
Acute safety study [114] 2000 mg/kg Polish Rats 22,580
DL50 determination [95] 3000 mg/kg Brazilian Mice 17,073
Biochemical parameters—30 days [95] 650 mg/kg Brazilian Rats 7338
Acute toxicity parameters** 2500 mg/kg Brazilian Wistar rats 28,225
Subchronic study (28 days)** 1000 mg/kg Brazilian Wistar rats 11,290
Subchronic study (28 days)** 100, 300 and
1000 mg/kg
Brazilian Rabbits 22,580
* Conversion considering adult weight around 70 kg.
** Results of our group and not published yet.
Table 4. Safety non‐clinical results for propolis administration for oral route.
According to Dobrowolski et al. [114], LD50 for dierent sources of propolis varied from 2 to
7.3 g/kg in mice, suggesting a safe dose for humans of 1.4 and 70 mg/day (when using safety
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
factor of 1000). In conclusion, considering Brazilian propolis LD50 as 17,073 mg/day for
humans [95], the application of a safety factor of 10 suggested by FDA guidelines, we would
have a safe dose of 1700 mg or 1.7 g/day of propolis for an adult.
4.2. Clinical studies
Khayyal et al. [115] evaluated propolis extract activity in asthmatic patients with oral admin‐
istration of 260 mg of propolis/day, for 2 months. The results demonstrated reduced night
aacks (2.5 aacks/week for 1/week) and improved ventilatory functions, as a consequence of
a decrease of TNF‐, ICAM‐1, IL‐6, and IL‐8, and an increase of 3· of IL‐10, besides a decrease
of prostaglandins E2, F2, and leukotriene D4.
Cohen et al. [116] evaluated 430 children aged 1–5 year old. Treated group (n=215) received a
mixture of echinacea (50 mg/ml), propolis (50 mg/ml), and vitamin C (10 mg/ml), during 12
weeks, and compared to the placebo group. Children aged 1–3 year old received 5.0 ml, 2·/day,
orally while children aged 4–5 year old received 7.5 ml. They were benets in the incidence
and severity of respiratory tract infections, with a decrease of 55% in the number of sick
children, 50% in the incidence of respiratory diseases, and 60% decrease in the number of days
with fever.
Type of study (oral route) Dosage Dosage
converted to
human adult
Double‐blind study with children—prevention
to respiratory infections
50 mg/ml—10 ml/day (children 1–3 year
2482.27 [116]
Double‐blind study with children—prevention
to respiratory infections
50 mg/ml—15 ml/day (children 4–5 year
2876.71 [116]
Pilot clinical trial with asthmatic volunteers 2–3 tablets/day with 88.4 mg propolis
265.20 [116]
Pilot clinical trial with healthy volunteers—
prophylactic study
500 mg propolis (2 capsules/day) 500.0 [117]
Pilot clinical trial—recurrent stomatitis 500 mg propolis/day 500.0 [118]
Propolis for wound healing 500 mg propolis/day 500.0 [119]
Clinical trial with asthmatic patients 1 sachet with 260 mg propolis/day 260.0 [115]
Pilot clinical trial with Brazilian propolis for
treatment of Helicobacter pylori
20 drops, 3× /day ˜350.0 [120]
Table 5. Clinical trials done with propolis administrated for oral route.
Bräer et al. [117] evaluated the oral administration of 500 mg of propolis for 13 days in healthy
volunteers focusing on the evaluation of the immune response (TNF‐α, IL‐6, and IL‐8). There
was an increased ability in the cytokines secretion, however, without plasmatic levels. Then,
prophylactic administration of propolis depends on the immune system reactivity and time,
with no adverse eects.
Superfood and Functional Food - An Overview of Their Processing and Utilization74
Samet et al. [118] tested the oral administration of 500 mg of propolis in a randomized, placebo‐
controlled double‐blind study, in which it was possible to demonstrate the benets of propolis
treatment in the repeated stomatitis, especially important in cases of resistance to treatment.
Finally, Zedan et al. [119] evaluated the administration of 500 mg of propolis/day in 45 patients
aiming to oer an alternative treatment to cutaneous healings. The study compared propolis
with echinacea and placebo, and propolis demonstrated to be more ecient than the other
groups, especially in usual and supercial healings (Table 5).
Jasprica et al. [121] studied the antioxidant eects of propolis (propolis soluble in water and
maltodextrin, 0.65 g of propolis, presenting 2.5% of avonoids, equivalent to 16.25 mg
expressed as galangin, Specchiasol, Italy) when administered in healthy volunteers (n=47,
women and men), 3 doses/day (total daily dose of 48.75 mg of avonoids) for 15 and 30 days,
with the following parameters under investigation: superoxide dismutase, glutathione
peroxidase, and catalase, malondialdehyde, total cholesterol, low‐ and high‐density lipopro‐
tein cholesterol, triglycerides, glucose, uric acid, ferritin and transferrin, and all routine red
blood cell parameters. Interestingly, only men with 30 days of treatment presented dierences
in malondialdehyde (decrease), superoxide dismutase activity (increase), and a few changes
in some parameters of red blood cell were detected.
Considering all the previously presented studies, it is possible to suggest that propolis dosages
ranging from 260.0 mg to 2.87 g, which have already been used in humans can be considered
safe. The biological results observed also varied much. Considering that propolis around the
world is largely used as a supplement or functional food, it is reasonable to assume that dosages
within this range will probably be safe, since none of the articles suggested any damage or
complications for the volunteers. Regarding the antioxidant evaluation proposed by Jasprica
et al. [121] in humans and the literature available until now, it is likely that the propolis dosage
used was very high for this purpose. Some data previously published suggested that propolis
can have a “pro” or “anti” action and, because several in vitro and in vivo studies demonstrated
antioxidant actions at certain does, it is possible that the best result may be achieved using
dosages around 500 mg/day successfully, but further investigation is needed.
5. Extraction technologies and innovation products
5.1. Extraction technology
Propolis is a very complex material depending on the vegetation present in the area visited by
bees. Besides the propolis source, the extraction process associated with solvents used will
denitely provide a completely dierent extract [20]. It is well established that chemical
compounds possess several particularities such as solubility, volatility, partition coecient oil/
water, pKa, and therefore, dierent solvents will probably extract dierent compounds [122].
Depending on the temperature and equipment necessary, volatile compounds can be lost and
then, it is common to use cold procedures such as maceration or percolation, and when it is
necessary to use higher temperatures, it is important to be careful in order to preserve every
compound of interest.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
Park and Ikegaki [122] studied propolis extracts obtained from water with 96% ethanol solution
as solvents. The results demonstrated that propolis extract obtained with 80% ethanol grade
showed higher absorption at 290 nm. Using ethanol solution at 60%, higher quantities of
isosakuranetin, quercetin, and kaempferol were extracted, while pinocembrin and sakuranetin
were beer extracted with ethanol solution at 70% and kaempferide, acacetin, and isorham‐
netin were most extracted with ethanol solution 80%. More expressive antimicrobial activities
were found in propolis extracts from 60 to 80% of ethanol solution extraction and higher
antioxidant results came from propolis extract obtained with ethanol 70–80%.
The most common extraction process for propolis to oral administration is the alcoholic (70%)
extraction using maceration, percolation and/or turboextraction. The ratio of propolis raw
material:extract used is completely variable and usually, in Brazil, 1:3–4, i.e., 1 part of propolis
raw material may oer 3 or 4 parts of extract, considering the production of a liquid extract
with at least 11%w/v of propolis dry maer. Of course, this ratio may vary and it is completely
dependent on the quality of propolis raw material used.
Jorge et al. [46] studied green propolis extracts obtained from four dierent locations in São
Paulo and Minas Gerais States, using the same extraction process, i.e., hydroalcoholic solution
70% with maceration for 30 days. Although all samples evaluated were Brazilian green
propolis using the same extract, dierent results were found for drupanin, baccharin, and
artepillin C during the same month, in spite of seasonal dierences. Therefore, it is possible to
conclude that, using the same oral source, solvent and process extraction, dierent regions,
and seasonal variations also oer a dierent chemical composition. Interestingly, these
dierences did not aect the safe of propolis ingestion [111].
Besides maceration, percolation or turboextraction, Trusheva et al. [123] compared ultrasound
extraction and microwave‐assisted extraction with the maceration process. The careful analysis
of the results obtained with each process demonstrated that statistical dierences were found
for total phenolics and propolis total extractable maer for ultrasound process (30 min) and
microwave (2 · 10 s) when compared to maceration extraction. For ultrasound, higher total
phenolics were found (52 3%) in comparison to maceration (43 2%) while the reduced total
extractable maer (53 3% versus 55%). In turn, microwave oered reduced values for total
phenolics (40.4 0.6% versus 43 2%) and expressively higher amounts of the total extractable
maer (75% versus 55%). Flavonoids analysis did not show important dierences among the
procedures evaluated. It is important to consider the time of extraction in each process, since
maceration takes around 72 h, and ultrasound was eective with 30 minutes and microwave
2 · 10 s. Another important thing is to dene the objective of the extraction: for analytical
purposes, it is more practical and cheaper to use ultrasound or microwave, however, for
industrial scale, these laer may not be easily implemented.
Propolis water extract was also obtained by some authors [12, 17, 98, 124] using completely
dierent procedures, demonstrating some interesting biological activities that had been
previously studied for propolis alcoholic extract, such as anti-inammatory [12], inhibition of
inammatory angiogenesis [98], and antiviral [17]. Although the demonstration of these
interesting results, chemical characterization was poorly explored in the manuscripts, except
by Urushisaki et al. [17] that presented the caeoylquinic derivatives as the most important
Superfood and Functional Food - An Overview of Their Processing and Utilization76
compounds of this extraction process; however, the manuscript does not present the extraction
process used. De Moura et al. [98] performed the extraction from propolis raw material
properly crushed in water maceration (500 ml) with temperature around 70°C (30–60 min),
two fractions were obtained from the same propolis raw material, followed by ltration. The
ltrate was then lyophilized. A similar procedure was used by others too. Nafady et al. [124]
in turn, used an innovative process with ‐cyclodextrin as encapsulate agent. To obtain this
extract, 10 g of crushed propolis was dispersed in 1 l of water containing 10 g of ‐cyclodextrin
previously dissolved. The inconvenient of this procedure is the elevate costs involved in the
acquisition of ‐cyclodextrin besides the limitation of the propolis concentration obtained in the
nal product. Machado et al. [12] proposed the extraction using hydroalcoholic solvent (70%)
as usual, however, the solvent was evaporated and after a hydrolysis step the propolis soft
extract was then resuspended in water, in this last case, the obtained extract demonstrated
similar chemical results of the alcoholic extract in the moment of preparation.
5.2. Nanoparticles and innovation products
Nowadays, nding natural additives has increased the eorts both to obtain bioactive
compounds from natural raw materials and develop stable and functional derivative products.
The former mentioned properties aributed to propolis are valuable and nd applications in
several industries, such as pharmaceutics, agrochemical, and food. The growing interest in
propolis has also promoted technological development for the suitable application of propolis.
Propolis in the powder form, for example, exhibits several advantages as increased concen‐
tration of propolis dry maer, higher chemical stability of the compounds, and longer
preservation of the biological properties. Additionally, the powder form also permits the
production of presentations with higher compliance in therapeutics, i.e., sachets, tablets, and
capsules. The drying process may also involve the encapsulation of the product resulting in
micro/nanoencapsulation systems, which can minimize sensory avor and odor and control
the release of the active compounds.
Propolis dry extract was obtained by Da Silva et al. [125] by employing arabic gum and octenyl
succinic anhydride (OSA) starch as carriers by spraydrier. The process allowed obtaining
propolis in the powder form with preserved antioxidant activity, stability, and low hygrosco‐
picity. Microencapsulated propolis extract obtained by complex coacervation was reached and
presented inhibitory activity against S. aureus [126]. Bruschi et al. [127] obtained gelatin
microparticles containing propolis extractive solution by spray‐drying technique. The
microencapsulation by spray‐drying technique maintained the activity of propolis against S.
aureus. In another study, the eect of spray drying parameters on the chemical and biological
properties of alcoholic extract of green propolis was investigated [128]. Several parameters of
the process demonstrated to inuence the polyphenol and avonoid content, as well as the
antioxidant activity, but under an optimized condition, the dried propolis extract showed
signicant antioxidant activity, with 50% lipid peroxidation inhibition at concentrations
ranging from 2.5 to 5.0 mg/ml.
More recently, Marquiafável et al. [129] aimed to develop a propolis dry extract with high
propolis (~40%w/w of propolis dry maer) and artepillin C contents by employing a combi‐
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
nation of silicon dioxide with arabic or modied starch and silicon dioxide by spray‐drier.
They have successfully obtained a standardized propolis extract with high amount of propolis,
avonoid content, expected amounts of artepillin C, and with maintained antibacterial activity,
and obtained microparticles with both excipients used. Recently, results of the same group
obtained dry extracts of propolis with 70–80% of dry maer; however, the microparticles were
not obtained (data not published yet), and then, the odor, color, and taste are not similarly
reduced as it is possible to observe when microparticles are obtained (Figure 10). Although
microparticles were not obtained with 70–80% of propolis dry maer, this extract is the most
concentrated one found in the market until now and can be used in several products with very
good results, for example soft or hard capsules or tablets.
Figure 10. Propolis standardized water extracts of green propolis; C: propolis standardized extract (EPP‐AF®).
In general, the propolis powder extracts obtained by spray‐drying technique investigated in
the literature demonstrated the formation of particles at the micrometer scale, from 1 to 10–20
μm. On the other hand, as nanotechnology can oer new opportunities for propolis applica‐
tion, in another line of research, nanosized particles have been developed. Patil et al. [130] have
obtained and characterized silver nanoparticles containing propolis [130]. Propolis nanopar‐
ticles have also been obtained employing lipid carriers. Our research group has focused on
developing solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) encapsu‐
lating propolis. Figure 11 shows atomic force microscopy (AFM) images of propolis‐loaded
NLC. Additional studies were also conducted covering NLC surface with chitosan. The
chitosan‐covered particles presented positive residual surface charge [≈ +40 mV], while the
uncoated ones presented negative charges [≈ −30 mV]. Particles were anisometric in shape and
approximately 150–200 nm in size. The images demonstrate the particle surface and conrm
the nanometric size of the particle. Additionally, no roughness was observed on the particle
Superfood and Functional Food - An Overview of Their Processing and Utilization78
Figure 11. Atomic force microscopy (AFM) images of propolis‐NLC (A) and chitosan coated propolis‐NLC.
Several important applications can be carried out with innovative propolis extracts. Dierent
presentations of propolis were previously showed as in a liquid presentation without alcohol,
usually using propylene glycol or polyethylene glycol, propolis powders in dierent systems
or concentrations, micro or nanoparticles, and others, as soft or hard capsules, with immediate
or sustained release systems. Considering the applications, it is possible to formulate capsules,
tablets, pills, or others with a specic amount of propolis dry maer, or with a focus on some
groups of compounds (total avonoid or polyphenols) and nally, on a biomarker or a group
of these substances such as artepillin C, drupanin, or baccharin, all presentations completely
applicable to functional or supplement food, or medicines. Besides oral administration, it is
possible to use all of these propolis presentations in topical products, as previously published
by Berrea et al. [8] who presented a propolis thermoreversible gel to treat cutaneous lesions
or burns, Barud et al. [131] with a propolis biomembrane for the same application, or Berrea
et al. [50] that demonstrated the benets of the application of a propolis mucoadhesive gel in
vulvovaginal candidiasis. Several other products can be found in the market and in the
literature, such as mouthwashes, toothpastes dental creams, among others.
6. Regulatory aairs
Functional food and natural health products have become an important part of people’s daily
diet, contributing to the general health of the population and boosting the global food industry.
Therefore, its importance is reected in the interest in regulation of health claims and standards
from industry stakeholders and policymakers.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
In this chapter, we examine propolis product regulations and policies in many important
producing and consuming countries around the world. The goal of this study is to incentive
legislators to update the regulation on propolis products in order to improve information
available to consumers so they can make beer choices and also be provided with healthier
and more innovative options.
The regulatory climate worldwide appears to be tending toward propolis classication into
the health food products category, although this category also has dierent names, registration
requirements, and allowed claims throughout the world.
Nevertheless, there are still some countries that categorize propolis as a conventional food
together with the other bee products, such as honey, royal jelly, and bee pollen. That is the case
of Brazil, where the product is regulated by the Ministry of Agriculture with very stringent
regulation that limits the product’s presentations, information to consumer and does not allow
health claims. In 2005, the Brazilian “National Health Surveillance Agency” (ANVISA)
published a technical note allowing the registration of propolis as a topical medicine with the
claims of anti-inammatory, antiseptic, and wound healing [132]. The publication of another
regulation [133] reinforced the same rules but, due to the very strict rules for medicines,
although Brazil is one of the biggest propolis markets, there are no propolis medicines
registered to this date.
In the United States, propolis is encompassed together with a wide range of substances by the
denition of a dietary supplement in the Dietary Supplement Health Education Act of 1994
(DSHEA) [134]. The use of function claims is also regulated by the above‐mentioned regulation
that established some special regulatory requirements and procedures for claims of general
well‐being. These claims are not preapproved by FDA, but the manufacturer must have
substantiation that the claim is truthful and not misleading and must submit a notication
with the text of the claim to FDA no later than 30 days after marketing the dietary supplement
with the claim.
In the European Union (EU), propolis belongs to the food supplement group, regulated by the
Directive 2002/46/EC [135], which denes the category as concentrated sources of nutrients or
other substances with a nutritional or physiological eect. Since 2006, EU has been engaged
in assessing generic health claims to surpass local regulation of member states and after this
harmonization product’s labels can only bear health claims authorized by the European Food
Safety Authority (EFSA) [136], which evaluates scientic data on claims provided by the
applicant. Up to this date, there is still no authorized health claim for propolis.
In Australia, all food supplements fall within the category of “complementary medicines”
under the Therapeutic Goods Act 1989 and the supporting Therapeutic Goods Regulations 1990
[137], in which the substances are evaluated according to their level of risk. It includes vitamin,
mineral, herbal, aromatherapy, and homeopathic products. A positive list of low‐risk substan‐
ces that may be used has been established and propolis is one of them. It can be used as an
active, excipient, or component in all listed medicine formulations. Propolis products can make
indications for health maintenance and health enhancement or certain indications for nonse‐
rious, self‐limiting conditions. It is the manufacturer responsibility to hold evidence to support
Superfood and Functional Food - An Overview of Their Processing and Utilization80
any indications as well as any other claims made for the medicine (according to Requirements
of section 26A of the Act).
Food supplements in Canada are regarded as “Natural Health Products” under the Natural
Health Products Regulations (SOR/2003‐196) [138–141] and may contain a wide range of
substances, such as vitamins and minerals, herbal remedies, homeopathic medicines, tradi‐
tional medicines, and probiotics. All products must be safe to use as over‐the‐counter products
and not need a prescription to be sold. Propolis is positive listed to be used orally in multiple
pharmaceutical dosage forms as a source of antioxidants for the maintenance of good health
and to help relieve sore throat and/or other mouth and throat infections. It can also be used
topically to assist in minor wound healing.
Japan is one of the rst countries to move toward regulating functional foods. There are lists
containing a broad range of substances that are not restricted to medicinal use and can therefore
be used in food supplements. Propolis in this scenario can be used as an authorized excipient
under the Food Sanitation Act 2010, as regular health food without any claims or as an active
of a “Food for Specied Health Uses” (FOSHU) [142] with health claims.
The Republic of Korea denes functional food signicantly dierently from other countries,
restricting functional food to nutraceuticals. They are regulated under the Health Functional
Food Act of 2004 [143] and there is a positive list in the Health Functional Food Code with 37
categories. Propolis preparations in all forms are allowed and may include two health claims:
antioxidant activity and antimicrobial activity in oral cavity.
The People’s Republic of China is another example of an Asian country that uses a product-
specic system of registration. The State Food and Drug Administration in China (SFDA) [144]
regulates these food supplements as “health foods” and maintains positive and negative lists
of substances that may be used in health foods. Propolis is in the positive list. There are 27
categories of health function claims approved by the SFDA, but the regulatory process for
achieving approval of these health claims is very strict and expensive, requiring the applicant
to conduct nonclinical or even clinical studies through an approved agency in addition to the
regular scientic literature review.
With this brief regulatory framework on propolis products, we have presented dierent
policies and regulations around the world and we hope that policymakers can improve the
regulatory scenario in the near future in order to accelerate and foster innovation in the sector.
7. Propolis nowadays market and potential
The green propolis has gained preference in the world market since the 1980s, unveiling new
horizons for the product. The growing interest of the market for green propolis in the context
of international food trade follows the increasing trend in search of healthier habits, which
have gained ample space in people’s daily lives all over the world.
In the Japanese market, green propolis has a high commercial value: according to SEBRAE,
the price of 1 kg of this product in 2010 was around $ 87 and the same amount of honey was
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
priced at about 3 dollars. In Tokyo’s market, this product is even more valued: a bole of green
propolis, in 2010, was sold for around $ 150 [145, 146]. In 2008, it was estimated that in Japan,
700 million dollars a year started to be moved by green propolis [147]. Japanʹs interest in green
propolis is justied not only by consumption: one of the most important examples of its use is
as an adjuvant in the treatment of cancer; but also by Japanese research related to the chemical
composition and biological activities of this type of propolis, especially studies with artepillin
C [16, 147].
The high demand for green propolis, especially from Asian countries, such as Japan, is essential
for sustaining the economy that revolves around this product, which is fairly lucrative. Green
propolis is produced mainly in the southeastern region, highlighting the state of Minas Gerais,
where there are over 8000 beekeepers, which produces more than 35 tons of propolis per year
[148]. These data show the importance of production and exports of green propolis, which is
one of the pillars of Brazilian apiculture economy.
Red propolis found in the Brazilian state of Alagoas has been internationally certied by the
Brazilian National Institute of Industrial Property (INPI) as the only producer of this kind of
propolis in the world and most of its compounds were not found in other types of Brazilian
propolis, which makes it a singular bee product [24]. Due to that, its commercial value is
internationally high. It has been reported that a kilogram of this product can cost around R
$ 500. Its importance to the Brazilian economy and to red propolis producer states is immeas‐
urable. Many propolis producers are being qualied and thereby, they are improving their
product quality and the production process. Like green propolis, red propolis is also highly
exported to Japan due to its chemical composition and biological eects [149].
Brazil is currently the worldʹs third largest producer of propolis, second only to Russia and
China [150]. Although it represents 10–15% of world production, Brazil fulll about 80% of
Japanese demand. Minas Gerais State (Brazil) Beekeepers Federation data show that the
propolis produced in the Midwest region of the state is considered the best in the world by
the Japanese market, where the kilogram of product has jumped from $ 5 to $ 200 in recent
years [150].
The propolis production in Brazil is estimated at around 140 tons, and the major part is destined
for international market, both in raw form and as nished products. It is estimated that 100
tons are green propolis and 40 tons other types of propolis. About 80% of the green propolis
produced in Brazil comes from the Midwest region of Minas Gerais State, close to the source
of the São Francisco river at Serra da Canastra, region where are the highest number of
producers. Despite the great Brazilian beekeeping potential, the current production is not
enough to fulll a growing global demand. The Brazilian honey bees are Africanized, pre‐
senting defensive and disease‐resistant features, with no need to use chemical treatments as
in other countries, which ensures Brazilian bee products excellent quality and free from
Many research fronts have been opened in the pursuit of development and adaptation of
professional management techniques in the production of green propolis. In addition to the
improvement actions and training of producers in beekeeping management practices, a group
Superfood and Functional Food - An Overview of Their Processing and Utilization82
of green propolis producers in the Midwest region of Minas Gerais in the Source of the São
Francisco River created an independent association supported by governmental agencies,
universities, researchers, and local private institution.
This association aims to establish the technical and scientic cooperation between the scientic
community and the beekeepers, aimed at regional development, improving the quality and
increasing the amount of green propolis produced in the region. Among the main projects
carried out, stand out the training of beekeepers in the professionalization of beekeeping,
conservation and cultivation of B. dracunculifolia elds, periodical replacement of old to
younger queen bees, and others projects. It is believed that the interaction of technical and
practical knowledge of beekeepers in conjunction with the application of scientic knowledge
by researchers and universities will contribute signicantly to a comprehensive training in the
professionalization of Brazilian beekeepers to fulll the goal of maintaining the quality and
increase the amount of green propolis produced in the region.
Trade promotion strategies are being constantly designed and implemented by the Brazilian
Association of Honey and Propolis Exporters (ABEMEL) and the Brazilian Trade and Invest‐
ment Promotion Agency (APEX‐Brasil) to disseminate Brazilian bee products around the
world. The result is the increasing demand from Asia, Europe, and North America countries.
In recent years, Brazil has been prominent on the international scene by winning important
prizes at the World Beekeeping Awards of Apimondia, the main world beekeeping event that
brings together representatives of over 130 countries and is held every 2 years. In the last
editions, Brazil won gold and silver medals in the category honey and gold in the category
8. Future perspectives
Considering all information presented here, it is easy to imagine the important potential of
propolis in the health of the population and in the Brazilian and international market,
especially because of the important biological activities and safety demonstrated with scientic
reports as in vitro”, in vivo,” and in some clinical trials. It is possible to generate several
innovative products in dierent elds considering food, cosmetics, and medicines, and this
choice obviously will be related to propolis dosages, formulations, and indications.
It is important to consider the investment in more clinical trials aiming to explore the benets
observed with traditional use and in animal studies, in order to rene the dosages and
formulations, with regard to the development of medicines. Besides clinical studies, another
important area is the improvement in the investments in productivity in eld, since the
Brazilian propolis available nowadays is not enough to supply all the countries that may be
interested in working with this fabulous natural material produced by bees with the support
of Brazilian Biodiversity. And nally, the eort of beepers and entities, such as ABEMEL, is
crucial to stimulate and support this work.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
We would like to thank Nivia Alcici, from Essenciale Propolis Company (Minas Gerais, Brazil),
for sending regulatory documentation of propolis of several countries, and also to the Brazilian
Association of Honey Exporter, ABEMEL, for nancial resources for the publication of this
Author details
Andresa A. Berrea1,2,3*, Caroline Arruda2, Felipe Galeti Miguel1, Nathalia Baptista1,
Andresa Piacezzi Nascimento1, Franciane Marquele‐Oliveira1, Juliana Issa Hori1,
Hernane da Silva Barud4, Bianca Damaso3,5, César Ramos3,5, Raul Ferreira1 and
Jairo Kenupp Bastos2
*Address all correspondence to: andresa.berrea@apis
1 Apis Flora Indl. Coml. Ltda., Ribeirão Preto, Brazil
2 Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão
Preto, Brazil
3 Brazilian Association of Honey Exporters, ABEMEL, Rio Claro, Brazil
4 Uniara, University of Araraquara, Araraquara, Brazil
5 Natucentro Própolis, Bambuí, Brazil
[1] Ghisalberti EL. Propolis: a review. Bee World. 1979;60:59–84.
[2] Ioirish N. As Abelhas: Bees: Pharmaceutical with Wings. Editora Mir: Moscou; 1982.
[3] Marcucci MC. Use of propolis in the cosmetic industry. Aerosol e Cosméticos. 1996;
[4] Bankova VS, Popov SS, Marekov NI. A study on avonoids of propolis. Journal of
Natural Products. 1982;46:471–474.
[5] Helfenberg KD. The analysis of beeswax and propolis. Chemiker Zeitungum.
Superfood and Functional Food - An Overview of Their Processing and Utilization84
[6] Iuliu P. Patente n. RO 48101, 1965.
[7] Salatino A, Fernanes‐Silva CC, Righi AA, Salatino MLF. Propolis research and
the chemistry of plant products. Natural Product Reports. 2011;28:928–925.
[8] Berrea AA, Nascimento AP, Bueno PCP, Vaz MMOLL, Marchei JM. Propolis
standardized extract (EPP‐AF®), an innovative chemically and biologically re‐
producible pharmaceutical compound for treating wounds. International Journal
of Biological Sciences. 2012;8:512–521. DOI: 10.7150/ijbs.3641.
[9] Nascimento AP, Ferreira NU, Barizon EA, Rocha BA, Vaz MMOLL, Berrea
AA. Methodologies for the evaluation of the antibacterial activity of propolis.
African Journal of Microbiology Research. 2013;7:2344–2350. DOI: 10.5897/
[10] Rocha BA, Bueno PCP, Vaz MMOLL, Nascimento AP, Ferreira NU, Moreno GP,
Rodrigues MR, Costa‐Machado ARM, Barizon EA, Campos JCL, de Oliveira PF,
Acésio NO, Martins SPL, Tavares DC, Berrea AA. Evaluation of a propolis
water extract using a reliable RP‐HPLC methodology and in vitro and in vivo
ecacy and safety characterisation. Evidence‐Based Complementary and Alternative
Medicine. 2013;2013 Article ID 670451. DOI: 10.1155/2013/670451.
[11] Marquele FD, Di Mambro VM, Georgei SR, Casagrande R, Valim YML, Fonseca
MJ V. Assessment of the antioxidant activities of Brazilian extracts of propolis
alone and in topical pharmaceutical formulations. Journal of Pharmaceutical and
Biomedical Analysis. 2005;39(3–4):455–462. 10.1016/j.jpba.2005.04.004.
[12] Machado JL, Assuncão AKM, Silva MCP, Reis AS, Costa GC, Arruda DS, Rocha
BA, Vaz MMOLL, Paes AMA, Guerra RNM, Berrea AA, do Nascimento FRF.
Brazilian green propolis: anti-inammatory property by an immunomodulatory
activity. Evidence‐Based Complementary and Alternative Medicine. 2012;2012:157652.
[13] Orsolić N, Knezević AH, Sver L, Terzić S, Basić I. Immunomodulatory and
antimetastatic action of propolis and related polyphenolic compounds. Journal
of Ethnopharmacology. 2004;94(2–3):307–315.
[14] Orsai CL, Missima F, Pagliarone AC, Bachiega TF, Búfalo MC, Araújo JP Jr,
Sforcin JM. Propolis immunomodulatory action in vivo on Toll‐like receptors 2
and 4 expression and on pro-inammatory cytokines production in mice.
Phytotherapy Research. 2010;24(8):1141–1146. DOI: 10.1002/ptr.3086.
[15] Hori JI, Zamboni DS, Carrão DB, Goldman GH, Berrea AA. The Inhibition
of inammasome by Brazilian Propolis (EPP‐AF). Evidence‐Based Complementary
and Alternative Medicine. 2013;2013:418508. DOI: 10.1155/2013/418508.
[16] Paulino N, Abreu SR, Uto Y, Koyama D, Nagasawa H, Hori H, Dirsch VM,
Vollmar AM, Scremin A, Bre WA. Anti-inammatory eects of a bioavailable
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
compound, Artepillin C, in Brazilian propolis. European Journal of Pharmacology.
2008;587(1–3):296–301. DOI: 10.1016/j.ejphar.2008.02.067.
[17] Urushisaki T, Takemura T, Tazawa S, Fukuoka M, Hosokawa‐Muto J, Araki Y, Kuwata
K (2011). Caeoylquinic acids are major constituents with potent anti-inuenza eects
in Brazilian green propolis water extract. Evidence‐Based Complementary and
Alternative Medicine. 2011;2011:254914. DOI: 10.1155/2011/254914.
[18] Daleprane JB, Freitas VS, Pacheco A, Rudnicki M, Faine LA, Dörr FA, Ikegaki M, Salazar
LA, Ong TP, Abdalla DSP. Anti‐atherogenic and anti‐angiogenic activities of polyphe‐
nols from propolis. Journal of Nutritional Biochemistry. 2002;23:557–566. DOI:10.1016/
[19] Santana LCLR, Carneiro SMP, Caland‐Neto LB, Arcanjo DDR, Moita‐Neto JM, Citó
AMGL, Carvalho FAA. Brazilian brown propolis elicits antileishmanial eect against
promastigote and amastigote forms of Leishmania amazonensis. Natural Product
Research: Formerly Natural Product Leers. 2002;28:5, 340–343. DOI:
[20] Sforcin JM, Bankova V. Propolis: is there a potential for the development of
new drugs? Journal of Ethnopharmacology. 2011;133:253–260. DOI: 10.1016/j.jep.
[21] Mello BCBS, Petrus JCC, Hubinger MD. Concentration of avonoids and phenolic
compounds in aqueous and ethanolic própolis extracts through nanoltration.
Journal of Food Engineering. 2010;96:533–539. DOI:10.1016/j.jfoodeng.2009.08.040.
[22] Ishida VFC, Negri G, Salatino A, Bandeira MFCL. A new type of Brazilian propolis:
prenylated benzophenones in propolis from Amazon and eects against cariogenic
bacteria. Food Chemistry. 2011;125:966–972. DOI:10.1016/j.foodchem.2010.09.089
[23] Park YK, Alencar SM, Aguiar CL. Botanical origin and chemical composition of
Brazilian propolis. Journal of Agricultural and Food Chemistry. 2002;50:2502–2506.
DOI: 10.1021/jf011432b
[24] Freires IA, Alencar SM, Rosalen PL. A pharmacological perspective on the use of
Brazilian Red Propolis and its isolated compounds against human diseases. European
Journal of Medicinal Chemistry. 2016;110:267–279. DOI: 10.1016/j.ejmech.2016.01.033
[25] Saito Y, Tsuruma K, Ichihara K, Shimazawa M, Hara H. Brazilian green propolis water
extract up‐regulates the early expression level of HO‐1 and accelerates Nrf2 after UVA
irradiation. BMC Complementary and Alternative Medicine. 2015;15:421. DOI 10.1186/
[26] Haori H, Okuda K, Murase T, Shigetsura Y, Narise K, Semenza GL, Nagasawa H.
Isolation, identication and biological evaluation of HIF‐1‐modulating compounds
from Brazilian green própolis. Bioorganic & Medicinal Chemistry 19, 2011; 5392–5401.
Superfood and Functional Food - An Overview of Their Processing and Utilization86
[27] Nakajima Y, Shimazawa M, Mishima S, Hara H. Water extract of propolis and its main
constituents, caeoylquinic acid derivatives, exert neuroprotective eects via antioxi‐
dant actions. Life Sciences. 2007;80: 370–377. DOI:10.1016/j.lfs.2006.09.017
[28] Figueiredo‐Rinhel ASG, Kabeya LM, Bueno PCP, Tiossi RFJ, Azzolini AEC S, Bastos JK,
Lucisano‐Valim YM. Inhibition of the human neutrophil oxidative metabolism by
Baccharis dracunculifolia DC (Asteraceae) is inuenced by seasonality and the ratio of
caeic acid to other phenolic compounds. Journal of Ethnopharmacology. 2013;150:
655–664. DOI:10.1016/j.jep.2013.09.019
[29] Castro ML, Cury JA, Rosalen PL, Alencar SM, Ikegaki M, Duarte S, Koo H. Propolis
from southeast and northeast of Brazil: inuence of seasonality on antibacterial activity
and phenolic composition. Quimica Nova. 2007;30:1512–1516. DOI: 10.1590/
[30] Lustosa SR, Galindo AB, Nunes LCC, Randau KP, Rolim Neto PJ. Propolis:
updates on chemistry and pharmacology. Revista Brasileira de Farmacognosia.
2008;18:447–454, 2008. DOI: 10.1590/S0102‐695X2008000300020
[31] Bankova V, Popova M, Trusheva B. Propolis volatile compounds: chemical diversity
and biological activity: a review. Chemistry Central Journal. 2014;8:28. DOI:
of the (E)‐Nerolidol and Other Volatile Compounds Within Ten Dierent Cultivated
Populations of Baccharis dracunculifolia D.C.(Asteraceae). The Journal of Essential Oil
Research. 2009;21: 308–314. DOI 10.1080/10412905.2009.9700179
[33] De Mendonça ICG, Porto ICCM, Do Nascimento TG, De Souza NS, Oliveira JMS,
Arruda RES, Mousinho KC, Dos Santos AF, Basílio‐Júnior ID, Parolia A, Barreto FS.
Brazilian red propolis: phytochemical screening, antioxidant activity and eect against
cancer cells. BMC Complementary and Alternative Medicine. 2015;15:357. DOI 10.1186/
[34] Fasolo D, Bergold AM, Poser GV, Teixeira HF. Determination of benzophenones in
lipophilic extract of Brazilian red propolis, nanotechnology‐based product and porcine
skin and mucosa. Analytical and bioanalytical assays. Journal of Pharmaceutical and
Biomedical Analysis. 2016. DOI:10.1016/j.jpba.2016.02.018.
[35] Righi AA, Alves TR, Negri G, Marques LM, Breyer H, Salatino, A. Brazilian red
propolis: unreported substances, antioxidant and antimicrobial activities. Journal of
the Science of Food and Agriculture. 2011;91:2363–2370. DOI 10.1002/jsfa.4468
[36] Nunes LC, Galindo AB, De Deus ASO, Runo DA, Randau KP, Xavier HS, Citó AMGL,
Rolim Neto PJ. Seasonal variability of the constituents of propolis and bioactivity in
saline Artermia. Brazilian Journal of Pharmacognosy. 2009;19:524–529. DOI:10.1590/
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
[37] Salatino A, Teixeira EW, Negri G, Message D. Origin and chemical variation
of Brazilian propolis. Evidence‐Based Complementary and Alternative Medicine.
2005;2:33–38. DOI:10.1093/ecam/neh060
[38] Bankova V, Marcuccib MC, Simova S, Nikolova N, Kujumgievc A, Popov S. Antibac‐
terial diterpenic acids from Brazilian propolis. Zeitschrift für Naturforschung.
[39] Sawaya ACHF, Tomazela DM,Cunha IBS, Bankova VS, Marcucci MC, Custodio AR,
Eberlin MN. Electrospray ionization mass spectrometry ngerprinting of Própolis.
Analyst. 2004;129:739–744. DOI: 10.1039/b403873h
[40] Huang S, Zhang CP, Wang K, Li GQ, Hu FL. Recent advances in the chemical
composition of propolis. Molecules. 2014;19:19610–19632. DOI:10.3390/mole‐
[41] Silva CSR, Barreto CLP, Peixoto RM, Mota RA, Ribeiro MF, Da Costa MM. Antibacterial
eect of Brazilian brown propolis in dierent solvents against staphylococcus spp.
Isolated from caprine mastitis. Ciência Animal Brasileira. 2012;13:247–251, 2012.
[42] Fonseca YM, Oliveira FM, Vicentini FTMC, Furtado NAJC, Sousa JPB, Valim YML,
Fonseca MJV. Evaluation of the potential of Brazilian propolis against UV‐induced
oxidative stress. Evidence‐Based Complementary and Alternative Medicine.
2011;2012:863917. DOI:10.1155/2011/863917
[43] Fernandes FH, Guterres ZR, Garcez WS, Lopes SM, Corsino J, Garcez FR. Assessment
of the (anti)genotoxicity of brown propolis extracts from Brazilian Cerrado biome in a
Drosophila melanogaster model. Food Research International. 2014;62:20–26. DOI:
[44] Fernandes FH, Guterresb ZR, Violante IMP, Lopes TFS, Garcez WS, Garcez F R.
Evaluation of mutagenic and antimicrobial properties of brown propolis essential oil
from the Brazilian cerrado biome. Toxicology Reports. 2015;2:1482–1488. DOI: 10.1016/
[45] Pimenta HC, Violante IMP, Musis CR, Borges AH, Aranha AMF.In vitro eectiveness
of Brazilian brown propolis against Enterococcus faecalis. Brazilian Oral Research
[online]. 2015;29(1):1–6. DOI: 10.1590/1807‐3107BOR‐2015.vol29.0058
[46] Jorge R, Furtado NAJC, Sousa JPB, Da Silva Filho AA, Gregório Júnior LE,
Martins CHG, Soares AEE, Bastos JK, Cunha WR, Silva MLA. Brazilian Propolis:
seasonal variation of the prenylated p‐coumaric acids and antimicrobial activity.
Pharmaceutical Biology. 2008;46:889–893. DOI: 10.1080/13880200802370373
[47] Fiordalisi SA, Honorato LA, Loiko MR, Avancini CA, Veleirinho MB, Machado
Filho LC, Kuhnen S. The eects of Brazilian propolis on etiological agents of
mastitis and the viability of bovine mammary gland explants. Journal of Dairy
Science. 2016;99:2308–2318. DOI: 10.3168/jds.2015‐9777
Superfood and Functional Food - An Overview of Their Processing and Utilization88
[48] Koo H, Gomes BPFA, Rosalen PL, Ambrosano GMB, Park YK, Cury JA. In vitro anti‐
microbial activity of propolis and Arnica montana against oral pathogens. Archives of
Oral Biology. 2000;45:141–148.
[49] De Luca MP, Franca JR, Macedo FAFF, Grenho L, Cortes ME, Faraco AAG, Moreira
AN, Santos VR. Propolis varnish: antimicrobial properties against cariogenic bacte‐
ria, cytotoxicity, and sustained‐release prole. Biomed Research International. 2014;
Article ID 348647. DOI: 10.1155/2014/348647
[50] Berrea AA, Castro PA, Cavalheiro AH, Fortes VS, Bom VP, Nascimento AP, Mar‐
quele‐Oliveira F, Pedrazzi V, Ramalho LNZ, Goldman GH. Evaluation of mucoadhe‐
sive gels with propolis (EPP‐AF) in preclinical treatment of candidiasis vulvovaginal
infection. Evidence‐Based Complementary and Alternative Medicine.
2013;2013:641480. DOI: 10.1155/2013/641480
[51] Castro PA, Savoldi MS, Bonao D, Barros MH, Goldman MHS, Berrea AA, Gold‐
man GH. Molecular characterization of propolis‐induced cell death in Saccharomyces
cerevisiae. Eukaryotic Cell. 2011;10:398–411. DOI: 10.1128/EC.00256‐10
[52] Siqueira ABS, Gomes BS, Cambuim I, Maia R, Abreu S, Souza-Moa CM, de Queiroz
LA, Porto ALF. Trichophyton species susceptibility to green and red propolis from
Brazil. Leers in Applied Microbiology. 2009;48:90–96. DOI: 10.1111/j.1472‐765X.
[53] Ngatu NR, Saruta T, Hirota R, Eitoku M, Luzitu NS, Muzembo BA, Matsui T, Suga‐
numa N. Brazilian green propolis extracts improve Tinea pedis interdigitalis and Tinea
corporis. Journal of Alternative and Complementary Medicine ed. 2012;18:8–9. DOI:
[54] Shimizu T, Takeshita Y, Takamori Y, Kai H, Sawamura R, Yoshida H, Watanabe W,
Tsutsumi A, Park YK, Yasukawa K, Matsuno K, Shiraki K, Kurokawa M. Ecacy of
Brazilian propolis against herpes simplex virus type 1 infection in mice and their
modes of antiherpetic ecacies. Evidence‐Based Complementary and Alternative
Medicine. 2011;2011:976196. DOI: 10.1155/2011/976196
[55] Takemura T, Urushisaki T, Fukuoka M, Hosokawa‐Muto J, Hata T, Okuda Y, Hori S,
Shigemi T, Araki Y, Kuwata K. 3,4-Dicaeoylquinic acid, a major constituent of Bra‐
zilian propolis, increases TRAIL expression and extends the lifetimes of mice infected
with the inuenza A virus. Evidence‐Based Complementary and Alternative Medi‐
cine. 2012;2012:946867. DOI: 10.1155/2012/946867
[56] Daugsch A, Moraes CS, Fort P, Pak YK. Brazilian red propolis—chemical composi‐
tion and botanical origin. Evidence‐Based Complementary and Alternative Medicine.
2008;5:435–441. DOI: 10.1093/ecam/nem057
[57] Inui S, Hatano A, Yoshino M, Hosoya T, Shimamura Y, Masuda S, Ahn MR, Tazawa S,
Araki Y, Kumazawa S. Identication of the phenolic compounds contributing to
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
antibacterial activity in ethanol extracts of Brazilian redpropolis. Natural Product
Research. 2014;28:1293–1296. DOI: 10.1080/14786419.2014.898146
[58] Machado BAS, Silva RPD, Barreto GA, Costa SS, da Silva DF, Brandão HN, da Rocha
JLC, Dellagostin OA, Henriques JAP, Umsza‐Guez MA, Padilha FF. Chemical compo‐
sition and biological activity of extracts obtained by supercritical extraction and etha‐
nolic extraction of brown, green and red propolis derived from dierent geographic
regions in Brazil. PLoS One. 2016;11:e0145954. DOI: 10.1371/journal.pone.0145954
[59] Das Neves MVM, da Silva TMS, Lima EO, da Cunha EVL, Oliveira EJ. Isoavone for‐
mononetin from red propolis acts as a fungicide against Candida sp. Brazilian Journal
of Microbiology. 2016;47:159–166. DOI: 10.1016/j.bjm.2015.11.009
[60] Kamuyama O, Abrão Júnior J, Teixeira JMA, De Andrade NJ, Minin VPR, Soares LS.
Extract of propolis in the sanitation and conservation of minimally processed carrots.
Revista Ceres. 2008;55(3):218–223.
[61] Borges CHF, Almeida DA, Fragiorge EJ. Antibacterial and antifungal activity of dif‐
ferent concentrations of propolis hydroalcoholic extract (EHP) in fresh pork sausage.
Food Engineering. 2009;6:53–82.
[62] Marquele‐Oliveira F, Fonseca YM, Georgei SR, Vicentini FTMC, Bronzati V, Fonseca
MJ V. Evaluation of the antioxidant activity as an additional parameter to aain the
functional quality of natural extracts. Latin American Journal of Pharmacy.
[63] Kumazawa S, Hamasaka T, Nakayama T. Antioxidant activity of propolis of various
geographic origins. Food Chemistry. 2004;84(3):329–339. DOI 10.1016/
[64] Duthie GG, Gardner PT, Kyle JAM. Plant polyphenols: are they the new magic bul‐
let? The Proceedings of the Nutrition Society. 2003;62(3):599–603. DOI 10.1079/
[65] Wang BJ, Lien YH, Yu ZR. Supercritical uid extractive fractionation—study of the
antioxidant activities of propolis. Food Chemistry. 2004;86(2):237–243. DOI 10.1016/
[66] Banskota AH, Tezuka Y, Kadota S. Recent progress in pharmacological research of
propolis. Phytotherapy Research. 2001;15:561–571. DOI 10.1002/ptr.1029.
[67] Shimizu K, Ashida H, Matsuura Y, Kanazawa K. Antioxidative bioavailability of arte‐
pillin C in Brazilian propolis. Archives of Biochemistry and Biophysics. 2004;424(2):
181–188. DOI 10.1016/
[68] Santos AC, Uyemura SA, Lopes JLC, Bazon JN, Mingao FE, Curti C. Eect of naturally
occuring avonoids on lipid peroxidation and membrane permeability transition in
mitochondria. Free Radical Biology & Medicine. 1998;24(9):1455–1461.
Superfood and Functional Food - An Overview of Their Processing and Utilization90
[69] Ozgová Š, Heřmánek J, Gut I. Dierent antioxidant eects of polyphenols on lipid
peroxidation and hydroxyl radicals in the NADPH‐, Fe‐ascorbate‐ and Fe‐microsomal
systems. Biochemical Pharmacology. 2003;66(7):1127–1137. DOI 10.1016/
[70] Campos JF, dos Santos UP, Macorini LFB, de Melo AMMF, Balestieri JBP, Par‐
edes‐Gamero EJ, et al. Antimicrobial, antioxidant and cytotoxic activities of prop‐
olis from Melipona orbignyi (Hymenoptera, Apidae). Food and Chemical
Toxicology. 2014;65:374–380. DOI 10.1016/j.fct.2014.01.008
[71] Siripatrawan U, Vitchayakii W, Sanguandeekul R. Antioxidant and antimicrobial
properties of Thai propolis extracted using ethanol aqueous solution. International
Journal of Food Science and Technology. 2013;48(1):22–7. DOI 10.1111/j.
[72] Graikou K, Popova M, Gori O, Bankova V, Chinou I. Characterization and bi‐
ological evaluation of selected Mediterranean propolis samples. Is it a new
type? Food Science and Technology. 2016;65:261–267. DOI 10.1016/j.lwt.2015.08.025.
[73] Tian H, Sun H, Zhang J, Zhang X, Zhao L, Guo S, et al. Ethanol extract of
propolis protects macrophages from oxidized low density lipoprotein‐induced apop‐
tosis by inhibiting CD36 expression and endoplasmic reticulum stress‐C/EBP ho‐
mologous protein pathway. BMC Complementary and Alternative Medicine.
BMC Complementary and Alternative Medicine; 2015;1–12. DOI 10.1186/
[74] Thorp E, Tabas I. Mechanisms and consequences of eerocytosis in advanced
atherosclerosis. Journal of Leukocyte Biology. 2009;86(5):1089–95. DOI 10.1189/jlb.
[75] Fonseca YM, Marquele‐Oliveira F, Vicentini FTMC, Furtado NAJC, Sousa JPB,
Lucisano‐Valim YM, et al. Evaluation of the potential of Brazilian propolis
against UV‐induced oxidative stress. Evidence‐Based Complementary and Alter‐
native Medicine. 2011;2011. 10.1155/2011/863917.
[76] Lopes AA, Ferreira TS, Nesi RT, Lanzei M, Pires KMP, Silva AM, et al. An‐
tioxidant action of propolis on mouse lungs exposed to short‐term cigaree
smoke. Bioorganic and Medicinal Chemistry. 2013;21(24):7570–7577. DOI 10.1016/
[77] Luis‐Villaroya A, Espina L, García‐Gonzalo D, Bayarri S, Pérez C, Pagán R. Bioactive
properties of a propolis‐based dietary supplement and its use in combination with mild
heat for apple juice preservation. International Journal of Food Microbiology.
2015;205:90–7. DOI 10.1016/j.ijfoodmicro.2015.03.020.
[78] Costa SS, Druzian JI, Aparecida B, Machado S, De CO, Guimara G. Bi‐Functional
biobased packing of the cassava starch, glycerol, licuri nanocellulose and red propolis.
PLoS One. 2014;9(11):e112554. DOI. 10.1371/journal.pone.0112554.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
[79] Fipatrick LR, Wang J, Le T. Caeic acid phenethyl ester, an inhibitor of
nuclear factor‐kappaB, aenuates bacterial peptidoglycan polysaccharide‐induced
colitis in rats. Journal of Pharmacology and Experimental Therapeutics. 2001;299(3):
[80] Ledón N, Casacó A, González R, Merino N, González A, Tolón Z. Antipsoriatic, anti-
inammatory, and analgesic eects of an extract of red propolis. Zhongguo Yao Li Xue
Bao. 1997;18(3):274–276.
[81] Menezes H, Alvarez JM, Almeida E. Mouse ear edema modulation by dierent propolis
ethanol extracts. Arzneimielforschung. 1999;49(8):705–707.
[82] Song YS, Park EH, Hur GM, Ryu YS, Kim YM, Jin C. Ethanol extract of propolis inhibits
nitric oxide synthase gene expression and enzyme activity. Journal of Ethnopharma‐
cology. 2002;80(2–3):155–161.
[83] Burdock GA. Review of the biological properties and toxicity of bee propolis (propolis).
Food and Chemical Toxicology. 1998;36(4):347–363.
[84] Hegazi AG, Abd El Hady FK, Abd Allah FA. Chemical composition and
antimicrobial activity of European propolis. Zeitschrift für Naturforschung C.
[85] Banskota AH, Tezuka Y, Prasain JK, Matsushige K, Saiki I, Kadota S. Chemical constit‐
uents of Brazilian propolis and their cytotoxic activities. Journal of Natural Prod‐
[86] Teixeira EW, Message D, Negri G, Salatino A, Stringheta PC. Seasonal variation,
chemical composition and antioxidant activity of Brazilian propolis samples. Evidence‐
Based Complementary and Alternative Medicine. 2010;7(3):307–315.
[87] Szliszka E, Kucharska AZ, Sokół‐Łętowska A, Mertas A, Czuba ZP, Król W. Chemical
composition and anti-inammatory eect of ethanolic extract of Brazilian green
propolis on activated J774A.1 macrophages. Evidence‐Based Complementary and
Alternative Medicine. 2013;2013:976415. DOI: 10.1155/2013/976415.
[88] Fischer G, Hubner SO, Vargas GD, and T. Vidor. Immunomodulation by Propolis.
Arquivos do Instituto Biológico. 2008;75:247–253.
[89] Bachiega TF, Orsai CL, Pagliarone AC, Sforcin JM. The eects of propolis and its
isolated compounds on cytokine production by murine macrophages. Phytotherapy
Research. 2012;26(9):1308–1313. DOI: 10.1002/ptr.3731.
[90] Sy LB, Wu YL, Chiang BL, Wang YH, Wu WM. Propolis extracts exhibit an immunor‐
egulatory activity in an OVA‐sensitized airway inammatory animal model. Interna‐
tional Immunopharmacology. 2006;6(7):1053–1060.
[91] Park EH, Kim SH, Park SS. Anti-inammatory activity of propolis. Archives of
Pharmacal Research. 1999;22(6):554–558.
Superfood and Functional Food - An Overview of Their Processing and Utilization92
[92] Mirzoeva OK, Calder PC. The eect of propolis and its components on eicosanoid
production during the inammatory response. Prostaglandins, Leukotrienes and Es‐
sential Fay Acids. 1996;55(6):441–449.
[93] Borrelli F, Maa P, Pinto L, Ianaro A, Russo A, Capasso F, Ialenti A. Phytochemical
compounds involved in the anti-inammatory eect of propolis extract. Fitoterapia.
[94] de Barros MP, Sousa JP, Bastos JK, de Andrade SF. Eect of Brazilian green propolis
on experimental gastric ulcers in rats. Journal of Ethnopharmacology. 2007;110(3):
[95] Reis, CM, Carvalho, JCT, Caputo, LRG. Anti-inammatory and antiulcer activity and
subchronic toxicity of propolis ethanolic extract. Revista Brasileira de Farmacogno‐
sia. 2000; (10):43–49.
[96] Tavares DC, Mazzaron Barcelos GR, Silva LF, Chacon Tonin CC, Bastos JK. Propolis‐
induced genotoxicity and antigenotoxicity in Chinese hamster ovary cells. Toxicology
In Vitro. 2006;20(7):1154–1158.
[97] Sforcin JM, Fernandes A Jr, Lopes CA, Bankova V, Funari SR. Seasonal eect on Bra‐
zilian propolis antibacterial activity. Journal of Ethnopharmacol. 2000;73(1–2):243–
[98] de Moura SA, Ferreira MA, Andrade SP, Reis ML, Noviello Mde L, Cara DC. Brazil‐
ian green propolis inhibits inammatory angiogenesis in a murine sponge model.
Evidence‐Based Complementary and Alternative Medicine. 2011;2011:182703. DOI:
[99] Bankova VS, de Castro SL, Marcucci MC. Propolis: recent advances in chemistry and
plant origin. Apidologie. 2000; (31):3–15.
[100] Kimoto T, Koya‐Miyata S, Hino K, Micallef MJ, Hanaya T, Arai S, Ikeda M, Kurimoto
M. Pulmonary carcinogenesis induced by ferric nitrilotriacetate in mice and protec‐
tion from it by Brazilian propolis and artepillin C. Virchows Archiv. 2001;438(3):259–
[101] Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK. Anti‐HIV‐1 activity of prop‐
olis in CD4(+) lymphocyte and microglial cell cultures. Journal of Ethnopharmacol.
[102] Messerli SM, Ahn MR, Kunimasa K, Yanagihara M, Tatefuji T, Hashimoto K, Mautner
V, Uto Y, Hori H, Kumazawa S, Kaji K, Ohta T, Maruta H. Artepillin C (ARC) in Brazilian
green propolis selectively blocks oncogenic PAK1 signaling and suppresses the growth
of NF tumors in mice. Phytotherapy Research. 2009;23(3):423–427. DOI: 10.1002/ptr.
[103] Zhao L, Pu L, Wei J, Li J, Wu J, Xin Z, Gao W, Guo C. Brazilian green propolis improves
antioxidant function in patients with type 2 diabetes mellitus. International Journal of
Environmental Research and Public Health. 2016;13(5). DOI: 10.3390/ijerph13050498.
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
[104] Fukuda T, Fukui M, Tanaka M, Senmaru T, Iwase H, Yamazaki M, Aoi W, Inui T, Na‐
kamura N, Marunaka Y. Eect of Brazilian green propolis in patients with type 2 dia‐
betes: a double‐blind randomized placebo‐controlled study. Biomedical Reports.
[105] Mazia RS, de Araújo Pereira RR, de Francisco LM, Natali MR, Dias Filho BP, Naka‐
mura CV, Bruschi ML, Ueda‐Nakamura T. Formulation and evaluation of a mucoad‐
hesive thermoresponsive system containing Brazilian green propolis for the
treatment of lesions caused by herpes simplex type I. Journal of Pharmaceutical Sci‐
ences. 2016;105(1):113–121. DOI: 10.1016/j.xphs.2015.11.016.
[106] Missima F, Sforcin JM. Green Brazilian propolis action on macrophages and lym‐
phoid organs of chronically stressed mice. Evidence‐Based Complementary and Al‐
ternative Medicine. 2008;5(1):71–75. DOI: 10.1093/ecam/nel112.
[107] Washio K, Kobayashi M, Saito N, Amagasa M, Kitamura H. Propolis ethanol extract
stimulates cytokine and chemokine production through NF‐κB activation in C2C12
myoblasts. Evidence‐Based Complementary and Alternative Medicine.
2015;2015:349751. DOI: 10.1155/2015/349751.
[108] Wu Z, Zhu A, Takayama F, Okada R, Liu Y, Harada Y, Wu S, Nakanishi H. Brazilian
green propolis suppresses the hypoxia‐induced neuroinammatory responses by in‐
hibiting NF‐κb activation in microglia. Oxidative Medicine and Cellular Longevity.
2013;2013:906726. DOI: 10.1155/2013/906726.
[109] Cho MS, Park WS, Jung WK, Qian ZJ, Lee DS, Choi JS, Lee DY, Park SG, Seo SK, Kim
HJ, Won JY, Yu BC, Choi IW. Caeic acid phenethyl ester promotes anti-inammato-
ry eects by inhibiting MAPK and NF‐κb signaling in activated HMC‐1 human mast
cells. Pharmaceutical Biology. 2014;52(7):926–932. DOI: 10.3109/13880209.2013.865243.
[110] Park MH, Kang DW, Jung Y, Choi KY, Min do S. Caeic acid phenethyl ester downre‐
gulates phospholipase D1 via direct binding and inhibition of NFκB transactivation.
Biochemical and Biophysical Research Communications. 2013;442(1–2):1–7. DOI:
[111] Sforcin JM, Kaneno R, Funari SRC. Absence of seasonal eect on the immunomodu‐
latory action of Brazilian própolis on natural killer activity. Journal of Venomous Ani‐
mals and Toxins. 2002;8(1). DOI.10.1590/S0104‐79302002000200005.
[112] Mani F, Damasceno HCR, Novelli ELB, Martins EAM, Sforcin JM. Propolis: eect of
dierent concentrations, extracts and intake period on seric biochemical variables.
Journal of Ethnopharmacology. 2006;105(1–2):95–98.
[113] Mohammadzadeh S, Shariatpanahi M, Hamedi M, Ahmadkhaniha R, Samadi N, Ostad
SN. Chemical composition, oral toxicity and antimicrobial activity of Iranian propolis.
Food Chemistry. 2007;103:1097–1103.
Superfood and Functional Food - An Overview of Their Processing and Utilization94
[114] Dobrowolski JW, Vohora SB, Sharma K, Shah SA, Naqvi SA, Dandiya PC. Antibacterial,
antifungal, antiamoebic, antiinammatory and antipyretic studies on propolis bee
products. Journal of Ethnopharmacology. 1991;35(1):77–82.
[115] Khayyal MT, El‐ghazaly MA, El‐khatib AS, Hatem AM, de Vries PJF, El‐shafei S,
Khaab MM. A clinical pharmacological study of the potential benecial eects of a
propolis food product as an adjuvant in asthmatic patients. Fundamental & Clinical
Pharmacology. 2003;17:93–102.
[116] Cohen HA, Varsano I, Kahan E, Sarrel EM, Uziel Y. Eectiveness of an herbal prepa‐
ration containing echinacea, propolis, and vitamin C in preventing respiratory tract
infections in children a randomized, double‐blind, placebo‐controlled, multicenter
study. Archives of Pediatrics and Adolescent Medicine. 2004;158:217–221.
[117] Bräer C, Tregel M, Liebenthal C, Volk HD. Prophylactic eectiveness of propolis for
immunostimulation: a clinical pilot study. Forsch Komplementmed. 1999;6(5):256–260.
[118] Samet N, Laurent C, Susarla SM, Samet-Rubinseen N. The eect of bee propolis on
recurrent aphthous stomatitis: a pilot study. Clinical Oral Investigations. 2007;11(2):
[119] Zedan H, Hofny ERM, Ismail SA. Propolis as an alternative treatment for cutaneous
warts. International Journal of Dermatology. 2009;48:1246–1249.
[120] Coelho LGV, Bastos EMAF, Resende CC, e Silva CMP, Sanches BSF, de Castro FJ,
Moresohn LD, Vieira WLS, Trindade OR. Brazilian green propolis on Helicobacter
pylori infection. A pilot clinic study. Helicobacter. 2007;12:572–574.
[121] Jasprica I, Mornar A, Debeljak Z, Smolcic‐Bubalo A, Medic‐Saric M, Mayer L, Romic Z,
Bucan K, Balog T, Sobocanec S, Sverko V. In vivo study of própolis supplementation
eects on antioxidative status and red blood cells. Journal of Ethnopharmacology.
[122] Park YK, Ikegaki M. Preparation of water and ethanolic extracts of propolis and
evaluation of the preparations. Bioscience Biotechnology and Biochemistry.
[123] Trusheva B, Trunkova D, Bankova V. Dierent extraction methods of biologically active
components from propolis: a preliminary study. Chemistry Central Journal. 2007;1(13):
1–4. Doi.10.1186/1752‐153X‐I‐13.
[124] Nafady AM, El‐Shanawany MA, Mohamed MH, Hassanean HA, Nohara T, Yoshimitsu
H, Ono M, Sugimoto H, Doi S, Sasaki K, Kuroda H. Cyclodextrin‐enclosed substances
of Brazilian própolis. Chemical Pharmaceutical Bulletin. 2003;51(8):984–985.
[125] Da Silva FC, Da Fonseca CR, De Alencar SM, Thomazini M, Balieiro JCDC, Piia P, et
al. Assessment of production eciency, physicochemical properties and storage
stability of spray‐dried propolis, a natural food additive, using gum Arabic and OSA
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
starch‐based carrier systems. Food and Bioproducts Processing. 2013;91(1):28–36. DOI
[126] Nori MP, Favaro‐Trindade CS, Matias de Alencar S, Thomazini M, de Camargo Balieiro
JC, Contreras Castillo CJ. Microencapsulation of propolis extract by complex coacer‐
vation. LWT: Food Science and Technology. 2011;44(2):429–35. DOI 10.1016/j.lwt.
[127] Bruschi ML, Cardoso MLC, Lucchesi MB, Gremião MPD. Gelatin microparticles
containing propolis obtained by spray‐drying technique: preparation and characteri‐
zation. International Journal of Pharmaceutics. 2003;264(1–2):45–55.
[128] Marquele FD, Stracieri KM, Fonseca MJ V, Freitas LAP. Spray‐dried propolis extract. I:
physicochemical and antioxidant properties. Pharmazie. 2006;61(4):325–330.
[129] Marquiafável FS, Nascimento AP, Barud H da S, Marquele‐Oliveira F, de‐Freitas LAP,
Bastos JK, et al. Development and characterization of a novel standardized propolis
dry extract obtained by factorial design with high artepillin C content. Journal of
Pharmaceutical Technology and Drug Research. 2015;4(1):1. DOI 10.7243/2050‐120x‐4‐1
[130] Patil S, Desai N, Mahadik K, Paradkar A. Can green synthesized propolis loaded silver
nanoparticulate gel enhance wound healing caused by burns? European Journal of
Integrative Medicine. 2015;7(3):243–250. DOI 10.1016/j.eujim.2015.03.002
[131] Barud HS, Araújo Júnior AM, Saska S, Mestieri LB, Campos JADB, de Freitas RM,
Ferreira NU, Nascimento AP, Miguel FG, Vaz Mmoll, Barizon EA, Marquele‐Oliveira
F, Gaspar AMM, Ribeiro SJL, Berrea AA. Antimicrobial Brazilian Propolis (EPP‐AF)
containing biocellulose membranes as promising biomaterial for skin wound healing.
Evidence‐Based Complementary and Alternative Medicine. 2013. Available from:
[132] Brazil, ANVISA. Technical Note on the Registration of Products Containing Propolis.
[Internet]. 2005. Available from: hp://
propolis.htm. Accessed August 22, 2016.
[133] Brazil, ANVISA. Resolution – RDC n. 24. De 14 De Junho De 2010 [Internet]. 2010.
Available from: hp://
RDC_24_2011.pdf/9a13f0fe-2e81-4fd1-9858-98eed4096813. Accessed August 22, 2016.
[134] United States, FDA. Dietary Supplement Health Education Act of 1994 (DSHEA)
[Internet]. 1994. Available from: hp://
default.htm. Accessed August 22, 2016.
[135] European Union, Directive 2002/46/EC of the European Parliament and of the council
of 10 June 2002 on the approximation of the laws of the Member States relating to food
supplements [Internet]. 2002. Available from: hp:// August 22, 2016.
Superfood and Functional Food - An Overview of Their Processing and Utilization96
[136] European Union, Regulation EC No. 1924/2006 of the Parliament and of the Council of
20 December 2006 on Nutrition and Health Claims Made on Foods [Internet]. 2006.
Available from: hp://
2007:012:0003:0018:EN:PDF.Accessed August 22, 2016.
[137] Australia. Therapeutic Goods Order No. 69 [Internet]. 2009. Available from: hps:// Accessed August 22, 2016.
[138] Canada. Natural Health Products Regulations (SOR/2003‐196) [Internet]. 2003. Avail‐
able from: hp:// Accessed
August 22, 2016.
[139] Canada. Monograph: Propolis—Oral [Internet]. 2014. Available from: hp:// Accessed August 22,
[140] Canada. Monograph: Propolis—Buccal [Internet]. 2014. Available from: hp:// Accessed
August 22, 2016.
[141] Canada. Monograph: Propolis—Topical [Internet]. 2014. Available from: hp:// Accessed
August 22, 2016.
[142] Japan. Specications and Standards for Foods, Food Additives, etc. Under
the Food Sanitation Act (Abstract) [Internet]. 2010. Available from: hps:// Accessed
August 22, 2016.
[143] South Korea. Functional Health Foods Act. [Internet]. 2014. Available from: hp://les/upload/eng/4_Health%20Functional%20Food%20Act.pdf.
Accessed August 22, 2016.
[144] South Korea. Health Functional Food Code. [Internet]. 2014. Available from: hp://les/upload/eng/7_Health%20Functioanl%20Food%20Codepdf.
Accessed August 22, 2016.
[145] Belmiro MS, Oki YY, Fernandes GW. 2011. Available from: hp://
mensagemdoce/112/artigo2.htm. Accessed June 12, 2015.
[146] SEBRAE. Brazilian Exportation of Propolis. Available from: hp://
%20Janeiro%202011.pdf. 2011. Accessed June 12, 2015.
[147] Nascimento EA, Chang R, Morais SAL, Piló‐Veloso D, Reis DC. An easily detectable
chemical marker for Propolis from Alecrim‐do‐campo (Baccharis dracunculifolia).
Revista Brasileira de Farmacognosia. 2008;18:379–386. DOI:/10.1590/
Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market
[148] FAEMG. High price of the propolis in the market. 2014. Available from: hp:// Accessed
June 12, 2015.
[149] BRASKEM. Red Propolis is recognized as an exclusive product of Brazil. 2012. Available
from: hps://
da-como-produto-exclusivo-do-Brasil. Accessed August 04, 2016.
[150] Pereira AS, Seixas FRMS, Aquino Neto FR. Propolis: 100 years of research and its future.
Química Nova. 2002;25(2): hp://
Superfood and Functional Food - An Overview of Their Processing and Utilization98
... Among the various types of propolis, green propolis (also known as Brazilian propolis) has received major attention in the international market since 1980 (Berretta et al. 2017). This high level of interest is partially due to the presence of over 150 different secondary metabolites in the composition of green propolis (Chang et al. 2008) with numerous therapeutic properties of high effectiveness such as antibacterial, antiviral, antitumor, and antioxidant activities as well as benefits against diabetes and respiratory, cardiac, and degenerative diseases. ...
... In the international market, green propolis is particularly renowned and consumed in Japan (Berretta et al. 2017). In addition to its pharmacological properties, the great demand for green propolis by the Japanese market is also attributed to the organoleptic characteristics of the natural product and the relatively lower content of heavy metals and other environmental pollutants (Pereira et al. 2002). ...
... Furthermore, the Africanized bees, A. mellifera, that produce green propolis are characterized as being more resistant to diseases, which reduces the need to subject the bees to chemical treatments, as is common in other countries. Ultimately, the absence of these chemical treatments guarantees a propolis of greater quality and free from potential chemical residue contamination (Berretta et al. 2017). ...
Propolis is a bee product that has wide pharmacological potential and has been used in several industrial sectors. Green propolis, a propolis derived from Baccharis dracunculifolia, has been highlighted for being a product with relevant pharmacological properties and high commercial value. To contribute to the formulation of policies for the regulation, production, and/or commercialization of propolis, this chapter searched for technologies and products involving propolis with emphasis on green propolis. The main countries, periods, and technological profiles of patents were identified, as well as manufacturers, types of products, and market value of propolis (all types) and green propolis. Patent registrations for propolis have been found on all continents, but especially in China where most are concentrated. Most patents are associated with health care, although most products are from the food and cosmetics industries. The value of products with propolis ranged from US$ 0.10 to US$ 1005.18 and a kilogram of raw propolis from US$ 26.42 to US$ 499.30. Japan presented the largest technological and industrial domain over green propolis. Even though Brazil is the exclusive producer of green propolis, the country is not a major technology developer. Brazil produces the greatest amount of products and the best raw materials in the world but stands out internationally only in the primary phase of the propolis production chain. Analysis of patents and products with propolis identified aspects of different stages of production and increased the understanding of the processes of development and production of items with this bee product.
... Propolis can reduce and ameliorate inflammatory diseases (Hori et al., 2013;Pineros et al., 2020) and has immunomodulatory properties (Ansorge et al., 2003). However, these properties may vary depending on the plant of origin of the propolis as well as the extractionprocess and inflammation protocol used (cell culture, animal models, lipopolysaccharide induction) when testing propolis extracts (Berretta et al., 2017). Animal model studies have shown that propolis can reduce levels of TNF and IL-6, and can increase levels of IL-10 (Machado et al., 2012). ...
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Currently, the number of cases and deaths of SARS-CoV2, especially among the chronic disease groups, due to aggressive SARS-CoV2 infection is increasing day by day. Various infections, particularly viral ones, cause a cytokine storm resulting in shortness of breath, bleeding, hypotension, and ultimately multi-organ failure due to over-expression of certain cytokines and necrosis factors. The most prominent clinical feature of SARS-CoV2 is the presence of elevated proinflammatory cytokines in the serum of patients with SARS-CoV2. Severe cases exhibit higher levels of cytokines, leading to a “cytokine storm” that further increases disease severity and causes acute respiratory distress syndrome, multiple organ failure, and death. Therefore, targeted cytokine production could be a potential therapeutic option for patients severely infected with SARS-CoV2. Given the current scenario, great scientific progress has been made in understanding the disease and its forms of treatment. Because of natural ingredients properties, they have the potential to be used as potential agents with the ability to modulate immune responses. Moreover, they can be used safely because they have no toxic effects, are biodegradable and biocompatible. However, these natural substances can continue to be used in the development of new therapies and vaccines. Finally, the aim and approach of this review article is to highlight current research on the possible use of natural products with promising potential as immune response activators. Moreover, consider the expected use of natural products when developing potential therapies and vaccines.
... Some countries, such as Brazil, Canada, the United States of America, China, South Korea, Japan, Australia, and the European Community, have already regulated propolis to improve the information available for their use (Berretta et al., 2017), and the total flavonoid and phenolic contents are some of the main chemical quality control parameters used for this product (Escriche & Juan-Borrás, 2018;Woisky & Salatino, 1998). In the case of Brazil, Normative Instruction n. 3 (2001) of the Ministry of Agriculture and Supply regulates the identity and minimum requirements that crude propolis and propolis extracts of A. mellifera and Meliponini must meet, instituting industrialization and commercialization measures for these products at national and international levels (Brazil, 2001). ...
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Although stingless bees are widespread in tropical and subtropical regions worldwide, their by-products, including propolis, are rarely used. In this study, we aimed to chemically analyze and investigate the potential of mid-infrared (MIR) spectroscopy and chemometric analyses for the authentication of propolis. The content of phenolic compounds and total flavonoids were used as quality parameters according to the guidelines of the Brazilian legislation. Attenuated total reflection-infrared (ATR-IR) spectroscopy was performed, and a chemo-metric model was developed and validated to discriminate and classify the four samples of propolis. The partial least squares-discriminant analysis (PLS-DA) model was found to be sensitive, specific, and accurate, and can be used for the quality control of these propolis samples for authentication purposes. Plebeia propolis showed the lowest total phenolic and flavonoid content. As suggested by the ATR-IR and confirmed by the determination of total phenolics and flavonoids, only green, tubuna, and mandaçaia propolis met the criteria established by the Brazilian legislation for marketing. In conclusion, the infrared chemometric model developed in this study can be implemented as a tool for the authentication of the studied propolis classes.
... Propolis is a resinous material collected from bud and exudates of the plants, mixed with bee enzymes, pollen, and wax (Sforcin, 2016;Cornara et al., 2017). Currently, it is widely consumed worldwide as a health aid and immune system stimulator, having been classified as a food or dietary supplement or as a functional/health food (Berretta et al., 2017). Vegetal and geographical origin determines the characteristics of different propolis and many different propolis types are known (Cornara et al., 2017). ...
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Except for specific vaccines and monoclonal antibodies, effective prophylactic or post-exposure therapeutic treatments are currently limited for COVID-19. Propolis, a honeybee’s product, has been suggested as a potential candidate for treatment of COVID-19 for its immunomodulatory properties and for its powerful activity against various types of viruses, including common coronaviruses. However, direct evidence regarding the antiviral activities of this product still remains poorly documented. VERO E6 and CALU3 cell lines were infected with SARS-CoV-2 and cultured in the presence of 12.5 or 25 μg/ml of a standardized Hydroalcoholic Extract acronym (sHEP) of Eurasian poplar type propolis and analyzed for viral RNA transcription, for cell damage by optical and electron microscopy, and for virus infectivity by viral titration at 2, 24, 48, and 72 h post-infection. The three main components of sHEP, caffeic acid phenethyl ester, galangin, and pinocembrin, were tested for the antiviral power, either alone or in combination. On both cell lines, sHEP showed significant effects mainly on CALU3 up to 48 h, i.e., some protection from cytopathic effects and consistent reduction of infected cell number, fewer viral particles inside cellular vesicles, reduction of viral titration in supernatants, dramatic drop of N gene negative sense RNA synthesis, and lower concentration of E gene RNA in cell extracts. Interestingly, pre-treatment of cells with sHEP before virus inoculation induced these same effects described previously and was not able to block virus entry. When used in combination, the three main constituents of sHEP showed antiviral activity at the same levels of sHEP. sHEP has a remarkable ability to hinder the replication of SARS-CoV-2, to limit new cycles of infection, and to protect host cells against the cytopathic effect, albeit with rather variable results. However, sHEP do not block the virus entry into the cells. The antiviral activity observed with the three main components of sHEP used in combination highlights that the mechanism underlying the antiviral activity of sHEP is probably the result of a synergistic effect. These data add further emphasis on the possible therapeutic role of this special honeybee’s product as an adjuvant to official treatments of COVID-19 patients for its direct antiviral activity.
... Despite representing 10 to 15% of world production, Brazil answers approximately 90% of Japanese demand. The commercial value of red propolis is generally five times higher than green (Berretta et al. 2017). In 2019, northeastern Brazilian beekeepers sold red propolis raw material at an average of US$150.00 per kilogram. ...
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Red propolis is a substance produced by bees by mixing resins from plants with wax, oils, and other secretions to protect the hive against natural enemies. Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) is the primary botanical source of the Brazilian red propolis, where bees Apis mellifera L. collect a reddish resin from the stems to produce propolis. This species occurs in coastal dune and mangrove ecosystems, where local beekeepers install their beehives for propolis production. The induction of propolis production was virtually unknown. Previous reports and field evidence suggested that the reddish resin available in D. ecastaphyllum stems was not produced spontaneously but induced by the presence of a parasitic insect that feeds on the plant's stems. Research in the apiaries of the beekeepers' association of Canavieiras, Bahia, Brazil, led to the capture of a jewel beetle of an unknown species of the genus Agrilus Curtis (Buprestidae). It was confirmed that this jewel beetle is a red propolis production inductor. The adult and immature of this new species, Agrilus propolis Migliore, Curletti, and Casari sp. nov. are here described and illustrated. Behavioral information on the biology and chemical ecology confirms that the reddish resin of D. ecastaphyllum is directly related to the beetle attack and only occurs when Agrilus propolis sp. nov. adults emerge from the plant stem. This information is very important for Brazilian propolis producers interested in expanding red propolis production, which can have favorable effects on the economy of mangrove communities, promoting income generation, creating new business opportunities, and helping to sustain local communities and families.
... However, found many restrictions were found for the approval and acceptance of these substances as a health-promoting supplement in various countries since these compounds e.g., propolis products are not standardized and vary in their components and biological activity among countries and even at a regional level, and therefore, faced many relevant criticism (Bankova, 2005;Toreti et al., 2013;Miguel et al., 2014). However, it should be stressed that standardized propolis products e.g., standardized Brazilian propolis extract blend have recently become available to overcome this major drawback and showed higher safety profile and major effectiveness for treatment of many pathological conditions (Berretta, 2007;Berretta et al., 2012;Berretta et al., 2017;Silveira et al., 2019;Zaccaria et al., 2019). Therefore, standardized propolis is considered an example for natural products that can be used a nutraceutical or functional food resource that might provide a promising safe and easy to administer therapeutic for fighting COVID-19 pandemic (Fielding et al., 2020). ...
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The recent emergence of COVID‐19 represents one of the biggest challenges facing the world today. Despite the recent attempts to understand the epidemiological pattern and pathogenesis of the disease, detailed data about the physiology and pathology of the disease is still out of reach. Moreover, the lack of a widespread vaccine prompts an urgent call for developing a proper intervention strategy against the virus. Importantly, identification of novel molecules that target replication of the virus represents one of the promising strategies for the control this pandemic crisis. Among others, honey bee products contain numerous bioactive compounds such as propolis and several phenolic compounds that possess a wide range of therapeutic properties for combating various pathological disorders and infectious agents. The intention of the present review is to highlight the stages of SARS-CoV-2 lifecycle, the molecular mechanisms explaining the health benefits of honey bee products on COVID‐19 physiology and pathology and the possible limitations. Further future research is suggested to explore more about bee natural bioactive compounds as potential candidates against SARS-CoV-2.
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This current study review provides a brief review of a natural bee product known as propolis and its relevance toward combat-ing SARS-CoV viruses. Propolis has been utilized in medicinal products for centuries due to its excellent biological properties. These include anti-oxidant, immunomodulatory, anti-inflammatory, anti-viral, anti-fungal, and bactericidal activities. Furthermore, studies on molecular simulations show that flavonoids in propolis may reduce viral replication. While further research is needed to validate this theory, it has been observed that COVID-19 patients receiving propolis show earlier viral clearance, enhanced symptom recovery, quicker discharge from hospitals, and a reduced mortality rate relative to other patients. As a result, it appears that propolis could probably be useful in the treatment of SARS-CoV-2-infected patients. Therefore, this review sought to explore the natural properties of propolis and further evaluated past studies that investigated propolis as an alternative product for the treatment of COVID-19 symptoms. In addition, the review also highlights the possible mode of propolis action as well as molecular simulations of propolis compounds that may interact with the SARS-CoV-2 virus. The activity of propolis compounds in decreasing the impact of COVID-19-related comorbidities, the possible roles of such compounds as COVID-19 vaccine adjuvants, and the use of nutraceuticals in COVID-19 treatment, instead of pharmaceuticals, has also been discussed.
Bee products have been used by humankind for their healthy attributes for many ages and applied as a traditional medicine in many countries. Nowadays, they are gaining more attention from different industry sectors, including pharmaceutical, dietary supplements, food, and cosmetics, based on technological and scientific developments due to the increasing demands of consumers for natural products. A vast amount of research demonstrated their valuable nutrients and bioactive compounds for many years and significantly contributed to the current knowledge, explaining the factors leading to variations in their contents and the significance of postharvest applications, like processing and storage; many scientific reviews illustrated the pharmaceutical value of their bioactive compounds with various biological properties. The obstacles relevant to their applications in food, dietary supplements, medicine, and cosmetics are discussed by focusing on the variation of their contents, needs for standardization of methodologies, and health claim approach at the global level. Current approaches for using propolis, pollen, royal jelly, and bee venom to develop therapeutic applications and many factors affecting their future like safe doses, toxicity, the bioavailability of nutrients, allergenicity, and health claim regulations are discussed together. Notably, the food and dietary supplement industry applications are emphasized by considering further research needs in that area. Outlook discussions are based on the trending research using computational tools for drug discovery to develop therapeutic agents from bee products, advanced analytical technology in enhancing the knowledge about their components and developing international standards, as well as the factors such as consumer demands, climate change, international trade, harmonization of standards, and safety.
Plants belonging to Baccharis genus (Asteraceae) have been used in folk medicine since ancient times. Usually, different Baccharis species are used in folk medicine as infusion or tea for gastrointestinal diseases, inflammation, ulcers, as an analgesic, spasmolytic, and antimicrobial, among others. Examples of medicinal plants from Baccharis are B. dracunculifolia D.C., B. illinita D.C., and B. trimera (Less.) DC., among many others. Over the years, these plants have been more studied: both chemical composition and biological activities. There are approximately 500 Baccharis species spread across the American continent, especially in South and Central America, which are important sources of bioactive compounds. The chemistry of these plants is characterized mainly by the presence of monoterpenes and sesquiterpenes in their essential oils. The nonvolatile fraction is characterized by diterpenes, triterpenes, and phenolic compounds, among others. Phenolic compounds are represented by phenylpropanoids, prenylated phenylpropanoids, flavonoids, flavonoid glycosides, coumarins, and simple phenolic compounds. In Baccharis spp. luteolin, chlorogenic acid, apigenin, acacetin, quercetin, kaempferol, p-coumaric acid derivatives, and coumarins have also been found. Many Baccharis spp. crude extracts and some of their isolated compounds were correlated with several biological activities. One example is the antioxidant effect of Brazilian Green Propolis, which is composed mainly of B. dracunculifolia compounds, such as flavonoid aglycones and p-coumaric acid derivatives, like artepillin C, baccharin, and drupanin. Baccharis spp. extracts display trypanocidal, antimicrobial, and anti-inflammatory activities, corroborating many folk medicinal uses. Therefore, in this chapter, an overview of the chemical composition is presented, highlighting the phenolic compounds of Baccharis spp., as well as its ethnopharmacological uses, in the light of many published scientific studies, focusing on the corroboration of folk uses. Furthermore, the toxicity of Baccharis species is discussed, which is a very important issue that is not well discussed in folk medicine: B. coridifolia, for example, is a poisonous plant responsible for necrosis of gastrointestinal tissue of rabbits and horses. Also, the chromatographic analyses of these plant extracts are addressed due to the importance of their chemical composition, the content of active compounds, and certainty of the correct botanical identification. In the final part, we conclude and discuss future perspectives for Baccharis extracts and their isolated compounds in the development of efficacious and safe medicines.
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This study aimed to evaluate the effectiveness of propolis extract as a natural preservative for livestock products in term of chemical and microbiological characteristics by meta-analysis. The stages carried out in this study were identification, selection, checking suitability, and the resulting selected articles were used in the meta-analysis. The selection results obtained a total of 22 selected journal articles consisting of 9 articles for analysis of the antimicrobial activity of propolis extract and 13 articles for analysis of the chemical and mirobiological characteristics of livestock products. The articles were obtained from electronic databases, namely Science Direct and Google Scholar. The model used in this study is the random-effect model involving two groups, control and experimental. Heterogeneity and effect size values were carried out in this study using Hedge's obtained through openMEE software. Forest plot tests and data validation on publication bias was obtained using Kendall's test throught JASP 0.14.1 software. The results showed that there is a significant relationship between propolis extract with the results of the antimicrobial activity (p<0.05). In addition, the results of the application of propolis extract on the livestock products for the test microbes and the value of thiobarbituric acid reactive substances (TBARs) showed significant results (p<0.05). Conclusion based on the random-effect model on the effectiveness of antimicrobial activity of propolis extract and their apllication as a natural preservative of the chemical and microbiological characteristics of livestock products is valid by Kendall's test (p>0.05). Propolis in this case effectively used as natural preservatives in livestock products.
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Propolis contains a variety of bioactive components and possesses many biological properties. This study was designed to evaluate potential effects of Brazilian green propolis on glucose metabolism and antioxidant function in patients with type 2 diabetes mellitus (T2DM). In the 18-week randomized controlled study, enrolled patients with T2DM were randomly assigned to Brazilian green propolis group (900 mg/day) (n = 32) and control group (n = 33). At the end of the study, no significant difference was found in serum glucose, glycosylated hemoglobin, insulin, aldose reductase or adiponectin between the two groups. However, serum GSH and total polyphenols were significantly increased, and serum carbonyls and lactate dehydrogenase activity were significantly reduced in the Brazilian green propolis group. Serum TNF-α was significantly decreased, whereas serum IL-1β and IL-6 were significantly increased in the Brazilian green propolis group. It is concluded that Brazilian green propolis is effective in improving antioxidant function in T2DM patients.
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A bioassay-guided fractionation of two samples of Brazilian red propolis (from Igarassu, PE, Brazil, hereinafter propolis 1 and 2) was conducted in order to determine the components responsible for its antimicrobial activity, especially against Candida spp. Samples of both the crude powdered resin and the crude ethanolic extract of propolis from both locations inhibited the growth of all 12 tested Candida strains, with a minimum inhibitory concentration of 256μg/mL. The hexane, acetate and methanol fractions of propolis 1 also inhibited all strains with minimum inhibitory concentration values ranging from 128 to 512μg/mL for the six bacteria tested and from 32 to 1024μg/mL for the yeasts. Similarly, hexane and acetate fractions of propolis sample 2 inhibited all microorganisms tested, with minimum inhibitory concentration values of 512μg/mL for bacteria and 32μg/mL for yeasts. The extracts were analyzed by HPLC and their phenolic profile allowed us to identify and quantitate one phenolic acid and seven flavonoids in the crude ethanolic extract. Formononetin and pinocembrin were the major constituents amongst the identified compounds. Formononetin was detected in all extracts and fractions tested, except for the methanolic fraction of sample 2. The isolated isoflavone formononetin inhibited the growth of all the microorganisms tested, with a minimum inhibitory concentration of 200μg/mL for the six bacteria strains tested and 25μg/mL for the six yeasts. Formononetin also exhibited fungicidal activity against five of the six yeasts tested. Taken together our results demonstrate that the isoflavone formononetin is implicated in the reported antimicrobial activity of red propolis.
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The variations in the chemical composition, and consequently, on the biological activity of the propolis, are associated with its type and geographic origin. Considering this fact, this study evaluated propolis extracts obtained by supercritical extraction (SCO2) and ethanolic extraction (EtOH), in eight samples of different types of propolis (red, green and brown), collected from different regions in Brazil. The content of phenolic compounds, flavonoids, in vitro antioxidant activity (DPPH and ABTS), Artepillin C, p-coumaric acid and antimicrobial activity against two bacteria were determined for all extracts. For the EtOH extracts, the anti-proliferative activity regarding the cell lines of B16F10, were also evaluated. Amongst the samples evaluated, the red propolis from the Brazilian Northeast (states of Sergipe and Alagoas) showed the higher biological potential, as well as the larger content of antioxidant compounds. The best results were shown for the extracts obtained through the conventional extraction method (EtOH). However, the highest concentrations of Artepillin C and p-coumaric acid were identified in the extracts from SCO2, indicating a higher selectivity for the extraction of these compounds. It was verified that the composition and biological activity of the Brazilian propolis vary significantly, depending on the type of sample and geographical area of collection.
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Biological, and particularly antimicrobial, activities have been demonstrated for the essential oil of propolis samples worlwide, yet their mutagenic effects remain unknown. To correlate antimicrobial effects with mutagenic risks, the present study evaluated the antifungal and antibacterial activities of the essential oil obtained from brown propolis collected from the Cerrado biome in Midwest Brazil (EOP), testing it against nine pathogenic microorganisms. Evaluation of mutagenic potential was based on the somatic mutation and recombination test (SMART) performed on wing cells of standard (ST) and high-bioactivation (HB) crosses of Drosophila melanogaster. EOP was extracted by hydrodistillation, and sesquiterpenes were characterized by GC–MS as its major constituents. The crude oil proved active against Cryptococcus neoformans and Enterococcus faecalis, as did two of its major constituents, spathulenol and (E)-nerolidol – the latter being also active against Staphylococcus aureus – isolated using chromatographic procedures. No significant increase in the number of somatic mutations was observed in the offspring of ST or HB crosses – the latter exhibiting enhanced levels of metabolizing enzymes of the cytochrome P450 type – treated with 0.05%, 0.1%, and 0.2% EOP. These findings revealed no mutagenic activity of EOP, even when tested against the HB strain, and demonstrated that its antimicrobial activities are not associated with DNA damage induction (investigated with SMART), suggesting the potential of EOP as a natural preservative.
Propolis is a complex resinous mixture collected by bees, with high medicinal, historical and economic value. The nutraceutical and pharmacological benefits of propolis have been extensively explored in several fields of medicine as an important resource for prevention and treatment of oral and systemic diseases. A relatively new type of propolis, named red propolis (in Brazil, Brazilian Red Propolis - BRP), has been arousing attention for the promising pharmacological properties of some of its isolated compounds (vestitol, neovestitol, quercetin, medicarpin, formononetin, etc). Due to a distinct chemical composition, BRP and its isolated compounds (mainly isoflavones) affect a wide range of biological targets and could have an impact against numerous diseases as an antimicrobial, anti-inflammatory and immunomodulatory, antioxidant and antiproliferative agent. In this review, we comprehensively address the main aspects related to BRP bioprospection, chemistry and therapeutic potential. Further information is provided on mechanisms of action discovered thus far as well as clinical use in humans and regulatory aspects. As of now, BRP and its isolated molecules remain a fascinating topic for further research and application in biomedical areas and dentistry.
The aim of the present work was to develop a topical delivery system that contains Brazilian green propolis extract (PE-8) to increase efficiency and convenience when applied to herpetic lesions. The cytotoxicity and antiherpetic activity was determined in vitro and in vivo. The PE-8 was added to a system that contained poloxamer 407 and carbopol 934P. The in vitro characterization of the system included rheological studies, texture profile analysis, and mucoadhesion analysis. The PE-8 inhibited the virus during the phase of viral infection, induced virion damage, and exhibited an ability to protect cells from viral infection. The system had advantageous mucoadhesive properties, including a suitable gelation temperature of approximately 25°C for topical delivery, a desirable textural profile, and pseudoplastic behavior. The in vitro release study showed a rapid initial release of the PE-8 in the first 3 h, and the rate of drug release remained constant for up to 24 h. The system appeared to be macroscopically and microscopically innocuous to skin tissue. Therefore, the mucoadhesive thermoresponsive system that contained the PE-8 appears to be promising for increasing bioavailability and achieving prolonged release of the PE-8 when applied to skin lesions caused by herpes simplex virus type 1.
The objective of this study was to evaluate in vitro the antimicrobial activity of Brazilian propolis from Urupema, São Joaquim, and Agua Doce (Santa Catarina State) and green propolis from Minas Gerais State, and the effects of propolis on bovine mammary gland explant viability. The propolis samples differed in flavonoid content and antioxidant activity. Green propolis showed the highest content of flavonoids, followed by the sample from São Joaquim. The propolis from Urupema showed the lowest flavonoid content along with the lowest antioxidant activity. The total phenolics were similar across all studied samples. Despite phytochemical differences, the propolis samples from Minas Gerais, São Joaquim, and Urupema presented the same level of antimicrobial activity against Staphylococcus aureus strains. The reduction in S. aureus growth was, on average, 1.5 and 4 log10 times at 200 and 500 μg/mL, respectively. At concentrations of 1,000 μg/mL, all propolis reduced bacterial growth to zero. On the other hand, when the propolis were tested against strains of Escherichia coli, the samples presented weak antimicrobial activity. Mammary explants were maintained in culture for 96 h without a loss in viability, demonstrating the applicability of the model in evaluating the toxicity of propolis. The origin and chemical composition of the propolis had an effect on mammary explant viability. We encountered inhibitory concentrations of 272.4, 171.8, 63.85, and 13.26 μg/mL for the propolis from Água Doce, Urupema, São Joaquim, and Mina Gerais, respectively. A clear association between greater antimicrobial activity and toxicity for mammary explants was observed. Of all propolis tested, the Urupema sample was noteworthy, as it showed antimicrobial activity at less toxic concentrations than the other samples, reducing bacterial growth to an average of 9.3 × 10(2) cfu/mL after 6 h of contact using 200 μg/mL of extract. The results demonstrate the potential for Brazilian propolis in the treatment of mastitis, although effectiveness is dependent on geographical origin and concentration. The results from the mammary gland explant assays are promising for the investigation of other natural products with antimicrobial and anti-inflammatory properties that can be used in the intramammary treatment of subclinical mastitis and during dry cow therapy.