The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several
Over the years, nature is continually surprising with diversified natural compounds that can be promising sources for the discovery of new drugs important in medicine [
Propolis, a complex mixture of compounds also called bee glue, is a natural resinous product that honeybees collect from several plants and mix it with beeswax and salivary enzymes (
Several
Propolis is not a new discovery. Since bee’s domestication, men explore its products to their own benefit and propolis, one of the most important chemical weapons of bees, is no exception, having been employed extensively since almost immemorial times [
Between the 17th and 20th century, this natural product became very popular in Europe. In 1969, in the former Union of Soviet Socialist Republics (USSR), the use of propolis was accepted in human and veterinary medicine, with several applications including the treatment of tuberculosis, where the regression of lung problems and recovery of appetite were observed. Also, it was believed to cure some diseases in folk Georgian medicine. During World War II (1939–1945), doctors used propolis to treat wounds [
Propolis is one of the few natural products that maintained popularity for a long time, although it is not considered a therapeutic agent in conventional medicine. Actually, it is widely used as a component in pharmaceutical and cosmetic products such as antiacne creams, facial and body creams, ointments and lotions, and several formulations for oral hygiene [
Propolis knowledge has registered an important evolution over time, due to exhaustive studies regarding its chemical composition and biological activities. In the 60s, it was thought that, despite its complexity, propolis chemical composition was more or less constant. Nevertheless, in the following years, analysis of a large number of samples from different geographic origins revealed that chemical composition of propolis is highly variable and also difficult to standardize because it depends on factors such as the vegetation, season, and environmental conditions of the site of collection [
Generally, the main constituents of propolis are resin and volatiles, which are substances obtained from a variety of botanical processes in different parts of plants, and beeswax, secreted by the bees [
Characteristic compounds of propolis from different geographic origins and respective plant source.
Geographic origin | Plant source | Typical constituents (main components) | References |
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Europe, North America, New Zealand, and temperate zones of Asia |
|
Pinocembrin, pinobanksin, chrysin, galangin, caffeic acid, ferulic acid, cinnamic acid, and their esters | [ |
Brazil | |||
Green propolis |
|
Prenylated phenylpropanoids, phenolic acids, prenylated |
[ |
Red propolis |
|
Formononetin, isoliquiritigenin, liquiritigenin, medicarpin, and biochanin A | [ |
Russia |
|
Cinnamic acids, phenylpropanoid sesquiterpenols, acacetin, apigenin, ermanin, rhamnocitrin, kaempferide, |
[ |
Cuba, Venezuela |
|
Polyisoprenylated benzophenones, more specifically nemorosone, xanthochymol, and guttiferone E | [ |
Mediterranean | |||
Greece | Probably |
Flavonoids, diterpenic acids such as isocupressic, pimaric, and communic acids, isoagatholal, agathadiol, ferruginol, 8-elemene, and totarol | [ |
Switzerland |
|
Benzyl |
[ |
Malta |
|
Diterpenic acids such as isocupressic, communic, pimaric, and imbricatoloic acid, together with totarol and 13-epitorulosal | [ |
Turkey |
|
Pinocembrin, pinobanksin and its acetate, prenyl esters of caffeic acid, ferulic acids, diterpenic acids like pimaric, isopimaric, abietic, dihydroabietic acids, cinnamyl cinnamate, and ethyl oleate, aromatic acid esters such as benzyl cinnamate, benzenedicarboxylic acid and flavanols such as benzopyran and chrysin | [ |
Algeria |
|
Pinocembrin, pinobanksin and its acetate, chrysin, apigenin, pectolinarigenin, pilosin, ladanein, galangin, naringenin, tectochrysin, methoxychrysin, prenyl esters of caffeic acids, ferulic acids, diterpenic acids like hydroxyditerpenic acid, labdane, and clerodane | [ |
Australia | |||
|
|
Xanthorrhoeol, pterostilbene, sakuranetin, pinostrobin, stilbenes, prenylated tetrahydroxystilbenes, prenylated cinnamic acids, flavanones, flavonols, chalcones | [ |
Stingless bee |
| ||
Africa | |||
Nigeria | Probably |
Isoflavonoids, prenylated isoflavonoids, and stilbenoids | [ |
Kenya | Triterpenes, arylnaphtalene lignans such as tetrahydrojusticidin B and 6-methoxydiphyllin, geranyl stilbenes, and geranylflavon macarangin | [ | |
Cameroon |
Triterpenes, derivatives of amyrin and lupeol and diprenyl flavonoids | [ | |
Oman |
|
Triterpenes, prenylated flavanones such as 7-O-methyl-8-prenylnaringenin, 3′,8-diprenylnaringenin, and 8-prenyl-5,7-dihydroxy-3′-(3-hydroxy-3-methylbutyl)-4′-methoxyflavanone, chalcones, cardanol, cardols, and anacardic acids | [ |
Ethiopia | Probably |
Triterpenoids such as |
[ |
Thailand |
|
Phenylallylflavanone, (E)-cinnamyl-(E)-cinnamylidenate | [ |
The Pacific region | |||
Okinawa, Hawaii, and Taiwan |
|
Prenylflavonoids, more specifically isonymphaeol-B, nymphaeol-A, nymphaeol-B, nymphaeol-C, propolins, 3′-geranyl-naringenin | [ |
Indonesia, Myanmar |
|
Alk(en)ylresorcinols, cycloartane-type triterpenes, cycloartanes, and prenylated flavanones | [ |
Canary Islands |
|
Furofuran lignans | [ |
Crude sample of propolis from Pereiro, obtained in the central region of Portugal (Guarda). The sample was kindly supplied by Engineer Pedro Fernandes (Mel do Abel).
Poplar-type propolis is undoubtedly the most studied one but there are many other propolis types. Recent studies have revealed a new type of European propolis: Mediterranean propolis. This type of propolis is distinguished by the high concentration of diterpenoids and is found in many regions like Greece [
Propolis from tropic regions, like Brazil, Cuba, Venezuela, and Chile, has been attracting much attention in the last years due to its particular chemical profiles. Prenylated phenylpropanoids, prenylated
Information about the chemical composition of Australian propolis is very limited despite the great biodiversity of the island. Propolis from Kangaroo Island is mainly composed of stilbenes, some of them being prenylated. Additionally, it has also some prenylated cinnamic acids and flavonoids [
“Pacific” propolis (e.g., Okinawa, Taiwan, Hawaii, Indonesia, and Myanmar) is another particular type of propolis. A new family of compounds, the prenylflavonoids, more specifically isonymphaeol-B, was identified in Okinawa propolis although three already known compounds—nymphaeol-A, nymphaeol-B, and nymphaeol-C—have also been isolated in three samples [
Propolis additionally contains minerals such as magnesium, calcium, iodine, potassium, sodium, copper, zinc, manganese, and iron; some vitamins like B1, B2, B6, C, E, and D, as well as provitamin A; a few fatty acids; and also some enzymes derived from bee glandular secretion or possibly from pollen like succinic dehydrogenase, adenosine triphosphatase, glucose-6-phosphatase, acid phosphatase,
Despite propolis popularity over time, it is not considered as a therapeutic agent in conventional medicine as the standardization of chemical composition and biological activity is lacking. Such standardization is indispensable for acceptance in the health system. Thus, characterization of different types of propolis according to its plant origin and corresponding chemical profile is mandatory. Studies about propolis bioactivity must start with chemical profiling of the extracts since that information is essential to have detailed and consistent comparative data between each type of biological activity and chemical data. This information allows extrapolating the possible activity and mechanism of action of new propolis under study and provides substantial clues for the development of new drug candidates [
In the last decades, several studies have demonstrated the biological and pharmacological actions of different worldwide propolis samples. The following sections summarize the recent published information about antibacterial and antifungal [
It is well known that an endogenous stimuli, like cellular metabolism, and exogenous agents like UV, toxins, and drugs, among others, generate reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), the superoxide anion (
In the last years, several studies have been performed to evaluate the antioxidant capacity of natural products. Propolis extracts, composed of different polyphenols, have been reported to possess a potent antioxidant activity [
Antioxidant activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells | Effect | References |
---|---|---|---|---|---|
Portugal (Serra de Bornes and Fundão) | European propolis/ |
Methanolic extract | Human erythrocytes | Decrease in lipid peroxidation | [ |
Free radical scavenging | [ | ||||
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Brazil | Propolis from the stingless bee |
PEE | Human erythrocytes | Free radical scavenging; inhibition of hemolysis and lipid peroxidation | [ |
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Portugal (Central Algarve) | European propolis/ |
PEE, PWE, and methanolic extracts | Free radicals scavenging, chelation of metal ions | [ | |
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Cuba | Red propolis |
Methanolic extract Nemorosone | Free radicals scavenging | [ | |
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Slovenia | European propolis/ |
PEE | Strong reducing power and ability to scavenge free radicals and metal ions | [ | |
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Romania | European propolis/ |
PEE | Female Swiss mice (UVB exposure) | Decrease in malondialdehyde levels, restoration of glutathione peroxidase activity | [ |
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Kangaroo Island | Australian propolis/ |
Ethyl acetate extract; stilbenes | Free radical scavenging | [ | |
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China | European propolis/ |
Ethyl acetate extract | Free radical scavenging and ferric reducing activity | [ | |
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Algeria | Mediterranean propolis |
Methanolic extract | Free radical scavenging and ferric reducing activity | [ | |
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Uruguay | European and green propolis/ |
PEE | Bovine aortic endothelial cells | Inhibition of low-density lipoprotein peroxidation and NADPH oxidase and increase in nitric oxide synthase | [ |
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Brazil | Green propolis/ |
PEE | C57BL/6 mice (acute lung inflammation caused by cigarette smoke) | Normalization of nitrite, myeloperoxidase levels, superoxide dismutase, catalase, and glutathione peroxidase activity and reduction of glutathione/oxidized glutathione ratio and malondialdehyde levels | [ |
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Turkey | Mediterranean propolis/ |
PEE | Fibroblast cells | Decrease of DNA damage induced by H2O2 | [ |
Male Wistar rats | Decrease in CAT activity and MDA levels in NOS inhibited rats | [ | |||
Carps ( |
Decrease in malondialdehyde levels, superoxide dismutase activity and increase of catalase and glutathione peroxidase activity | [ | |||
|
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Purchased from Sigma Aldrich Co. | Characteristic of European type propolis | CAPE | Free radical scavenging, inhibition of xanthine oxidase activity and lipid peroxidation | [ | |
Male Wistar albino rats | Maintenance of superoxide dismutase activity, decrease of xanthine oxidase activity and malondialdehyde and nitric oxidase levels | [ | |||
Peripheral blood mononuclear cells from cyclists | Reduction of hyperthermia-induced survival inhibition, necrosis, superoxide production, glutathione depletion, and intracellular superoxide | [ |
Moreira et al. [
Antioxidant activity is one of the most studied and important activities of propolis, though there are no studies with data on the safe dose to be used in humans. Thus, clinical studies using propolis and its active compounds are needed.
Inflammation is an event that normally occurs in response to the constant exposure to environmental and endogenous stimuli as well as to accidental damage [
Several studies have associated different types of propolis and its various constituents with anti-inflammatory activity [
Anti-inflammatory mechanisms investigated with propolis.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells | Effect | References |
---|---|---|---|---|---|
Purchased: Sigma Aldrich Co. |
Characteristic of European, Brazilian, and Mediterranean propolis | Caffeic acid, quercetin, naringenin; |
Peritoneal macrophages | Suppression of lipoxygenase pathway of arachidonic acid metabolism |
[ |
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Croatia | European propolis/ |
Water-soluble derivatives | Swiss albino mice | Reduction of DNA damage in peripheral lymphocytes | [ |
PEE | Male Swiss albino mice | Suppression of functional activity of macrophages | [ | ||
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Purchased: Sigma Aldrich Co. | J774 macrophages, Male Wistar rats |
|
[ | ||
Male Wistar albino rats | Decrease of polymorphonuclear neutrophilic leukocyte infiltration in the lungs tissues | [ | |||
Characteristic of European type propolis | CAPE | Gastric epithelial cell line (AGS), |
Inhibition of |
[ | |
Purchased: Wako Pure Chemical Industries, Ltd. | RAW264.7 macrophages | Decrease of the production of interleukin-1 |
[ | ||
Male Swiss inbred strain mice | Decrease of cyclooxygenase 2 expression, NF- |
[ | |||
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Brazil | Green propolis/ |
PEE | RAW264.7 macrophages | Downregulation of NF- |
[ |
Purchased: Acros Organics | Characteristic of European, Brazilian, and Mediterranean propolis | Caffeic acid | |||
|
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Brazil | Green propolis/ |
PEE | Sprague-Dawley rats | Inhibition of carrageenan-induced rat hind paws edema and the chemotaxis of human polymorphonuclear leukocytes (PMNs) | [ |
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Synthesized | Characteristic of European type propolis | CAPE | Polymorphonuclear leukocytes obtained from Human blood | Inhibition of 5-lipoxygenase activity and arachidonic acid release | [ |
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Chile | European propolis/poplar trees | PEE | Male CF-1 mice | Inhibition of NO release by the macrophages | [ |
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China | European propolis/ |
PEE and PWE | Male ICR mice and male Wistar rats | Inhibition of the activation and differentiation of mononuclear macrophages; decrease prostaglandin-E2 (PGE 2) and nitric oxide (NO) levels | [ |
|
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Brazil | Green propolis/ |
PWE | Swiss and BALB/c mice | Decrease in the number of macrophages and neutrophils; inhibition of proinflammatory cytokines and increase of anti-inflammatory cytokines | [ |
Red propolis/ |
PEE | Male Wistar rats | Decrease in renal macrophage infiltration in rats with chronic kidney disease | [ | |
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Nepal | Nepalese propolis/probably |
PEE, 3′,4′-dihydroxy-4-methoxydalbergione, 4-ethoxydalbergion, cearoin, and chrysin | Bone marrow-derived mast cells (BMMC) from C57BL/6 mice | Inhibiting IL-6, TNF- |
[ |
The release and oxygenation of arachidonic acid are a critical event in inflammation. Mirzoeva and Calder [
Natural substances are considered alternative adjuvant therapies in the treatment of different diseases due to their immunomodulatory effects. Information about this type of activity was scarce for propolis until the 1990s; but published work in the last years has provided information about the influence of different propolis samples on the immune system [
Immunomodulatory activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells | Effect | References |
---|---|---|---|---|---|
Brazil | Green propolis/ |
PEE | Male BALB/c mice | Upregulation of toll-like receptor-2 and receptor-4 expression and increases in interleukin-1 and interleukin-6 production | [ |
Upregulation of toll-like receptor-2 and receptor-4 mRNA expression | [ | ||||
Male C57BL/6 mice, B16F10 cell line | Stimulation of the expression and production of interleukin-2 and interleukin-10 and Th1 cytokine (interleukin-2 and IFN- |
[ | |||
Male BALB/c mice | Inhibition of Th1 cells generation; reduction of the frequency of IFN- |
[ | |||
Male BALB/c mice | Increase of H2O2 generation and decreases in the NO generation in peritoneal macrophages | [ | |||
Male BALB/c mice | Increase in the interiorization and killing of the parasites |
[ | |||
Monocytes from human blood | TLR-4 and CD80 expression in human monocytes as well as TNF- |
[ | |||
Melanoma cells (B16F10); male C57BL/6 mice | Reduction of IL-1 |
[ | |||
|
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Brazil |
Green propolis/ |
PEE, |
Male BALB/c mice | Stimulation of interleukin-1 |
[ |
|
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Purchased: Acros Organics | Characteristic of European, Brazilian, and Mediterranean propolis | Caffeic acid | Monocytes from human blood | Stimulation of monocytes activity against |
[ |
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Purchased: Acros Organics | Characteristic of European, Brazilian, Russian, Mediterranean, and Australian type propolis | Cinnamic acid | Monocytes from human blood | Downregulation of toll-like receptor-2, HLA-DR molecules from human antigen-presenting cells, and CD80; upregulation of toll-like receptor-4, inhibition of TNF- |
[ |
Purchased: Sigma Aldrich Co. | Cinnamic acid | Female IRC mice | Increase of lymphocyte proliferation and release of cytokines interleukin-1 and interleukin-2 | [ | |
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Brazil | Green propolis/ |
Hydroalcoholic (HPE) solution | Male BALB/c mice | Increase of H2O2 generation and decrease of NO generation | [ |
Male BALB/c mice | Decrease of splenocyte proliferation and increase of IFN- |
[ | |||
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Indonesia | The Pacific region propolis/ |
HPE | Male BALB/c mice | Increase of IgG generation and macrophage phagocytosis activity and capacity | [ |
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Turkey | Mediterranean propolis |
PEE | Peripheral blood mononuclear cells from healthy humans | Suppression of neopterin release and tryptophan degradation, downregulation of the enzyme indoleamine 2,3-dioxygenase (IDO) and decrease of IFN- |
[ |
|
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Purchased: Sigma Aldrich Co. | Characteristic of European type propolis | CAPE | Human monocyte-derived dendritic cells (MoDCs) generated from peripheral monocytes | Inhibition of IL-12 p40, IL-12 p70, IL-10, IFN- |
[ |
Female BALB/c mice | Increase of IgM antibody production, T lymphocyte proliferation, interleukin-4 and interleukin-2 production by splenocytes, and IFN- |
[ | |||
Human peripheral blood mononuclear cells, jurkat cells | Inhibition of transcription factors NF- |
[ |
In a study using Brazilian green propolis, it was seen that the administration for 3 days of a PEE to male BALB/c mice modulated the activation of the initial steps of the immune response by upregulating toll-like receptor- (TLR-) 2 and toll-like receptor-4 expression and proinflammatory cytokines (IL-1 and IL-6) production by macrophages and spleen cells [
Additionally, Missima et al. [
The immunomodulatory action of propolis does not occur only at the macrophage level. In fact, some studies show that this action has also an effect on lymphocyte proliferation [
Propolis comprises a complexity of compounds which play a role in antiviral protection. Despite the few data available regarding this activity, it was shown that propolis from different geographic regions has considerable antiviral activity by acting at different levels and interfering with the replication of some viruses [
Antiviral activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells/viruses | Effect | References |
---|---|---|---|---|---|
Purchased: Sigma Aldrich Co. | Characteristic of European type propolis | Caffeic acid, |
RC-37 cells, herpes simplex virus type 1 (HSV-1) strain KOS | High anti-HSV-1 activity for both extracts when cells were treated prior to viral infection | [ |
Czech Republic | European propolis/ |
PEE and PWE | RC-37 cells, herpes simplex virus type 2 (HSV-2) | High antiherpetic activity for both extracts when viruses were pretreated prior to infection | [ |
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Brazil | Brown propolis/ |
HPE | HSV-2 strain propagated in Vero cells, female BALB/c mice | Effective against HSV-2 infection and in reducing extravaginal lesions by acting on inflammatory and oxidative processes; reducing reactive species, tyrosine nitration, ascorbic acid levels, and myeloperoxidase activity and protecting against inhibition of catalase activity | [ |
Characteristic of Brazilian propolis | Isopentyl ferulate (isolated from an PEE) | Influenza viruses A/PR/8/34 (H1N1), A/Krasnodar/101/59 (H2N2), and A/Hong Kong/1/68 (H3N2) | Suppression of influenza virus A/Hong Kong reproduction |
[ | |
Green propolis/ |
PEE | Influenza A/PR/8/34 (H1N1) virus propagated Madin-Darby canine kidney (MDCK) cells, female DBA/2 Cr mice | Reduction of body weight loss of infected mice and virus yields in the bronchoalveolar lavage fluids of lungs | [ | |
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France | European propolis/ |
PEE | RC-37 cells, HSV-1 strain H29S, acyclovir resistant mutant HSV1-R strain H29R, HSV-2, adenovirus type 2, poliovirus type 2, and vesicular stomatitis virus (VSV) | Reduction of titre of herpes virus, being vesicular stomatitis virus and adenovirus less susceptible; virucidal action on the enveloped viruses HSV and VSV | [ |
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Brazil | Geopropolis from the stingless bee |
Hydromethanolic extract | African green monkey kidney cells (ATCC CCL-81); herpes simplex virus strain (McIntyre) | Inhibition of HSV replication and entry into cells | [ |
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Synthesized | Characteristic of Brazilian red and green propolis | Homoisoflavonoids, specially 3-benzyl-4-chromones | BGM (Buffalo Green Monkey) cells, coxsackie viruses B3, B4, and A9 and echovirus 30 | Good antiviral activity against the coxsackie viruses B3, B4, and A9 and echovirus 30 | [ |
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Canada | European propolis/ |
PEE | HSV-1 and HSV-2 virus replicated in MDBK (monolayer cultures of Madin-Darby bovine kidney) cells | Impairing the ability of the virus to adsorb or to penetrate the host cells | [ |
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Brazil | Green propolis/ |
Water extracts | Female BALB/c mice, Influenza A virus strain A/WSN/33 (H1N1) | Extension of the lifetime of mice. 3,4-dicaffeoylquinic acid which increases mRNA levels of tumor necrosis factor-related apoptosis-inducing and decreases H1N1 hemagglutinin mRNA |
[ |
Characteristic of Brazilian green propolis | 3,4-Dicaffeoylquinic acid (Isolated from Brazilian propolis) | ||||
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Brazil | Characteristic of Brazilian green propolis | Melliferone, moronic acid, anwuweizonic acid, and betulonic acid (isolated from Brazilian propolis) | H9 lymphocytes, HIV-1 | Moronic acid inhibiting anti-HIV replication | [ |
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Israel | Mediterranean propolis |
PWE | Jurkat, uninfected human T-cell lines, and MT2 (HTLV-1 infected human T cells) cells | Inhibition of the activation of NF- |
[ |
Purchased: Sigma Aldrich Co. | Characteristic of European propolis | CAPE | |||
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Provided by Binzhou Animal |
Nanometer propolis Flavone | Kidney cells (PK-15) |
Inhibition of PPV infecting porcine kidney- (PK-) 15 cells |
[ | |
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USA and China | European propolis/ |
PEE | Peripheral blood mononuclear cells obtained from blood of healthy donors, microglial cells isolated from human fetal brain tissue, HIV-1AT, HIV-1SF162 | Inhibition of HIV-1 variants expression |
[ |
Brazil | Green propolis/ |
Schnitzler et al. [
Over recent years, therapeutic benefits of propolis and/or its isolated compounds have been described in HIV treatment. Ito et al. [
Antimicrobial activity, one of the most studied propolis biological properties, is very well documented. This bioactivity has been largely investigated in the last years due to the need of new treatments against infectious diseases, especially with the increase of resistant pathogens to current antibiotics. Tables
Antibacterial activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species | Effect | References |
---|---|---|---|---|---|
Purchased: Bee Health Ltd. (Scarborough, Yorkshire, UK); | European propolis/ |
PEE |
|
Influencing the ion permeability of the inner bacterial membrane; |
[ |
Purchased: Sigma |
Characteristic of European, Brazilian, and Mediterranean propolis | Caffeic acid, CAPE, quercetin, and naringenin | |||
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Greece | Mediterranean propolis/probably |
Terpenes (isolated from Cretan propolis) |
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Influencing the Gram-positive and Gram-negative bacteria viability | [ |
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France | European propolis/ |
Dichloromethane extract | Gram-negative: 7 |
Influencing the Gram-positive bacteria viability specially |
[ |
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Bulgaria | Mediterranean propolis | PEE |
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Decrease of |
[ |
Greece |
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Turkey |
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Algeria |
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Australia | Australian propolis from stingless bee |
PEE |
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Inhibition of |
[ |
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Cameroon and Congo | African propolis/probably |
PEE |
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Inhibition of |
[ |
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Brazil | Green propolis/ |
PEE |
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Decrease of |
[ |
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Czech Republic | European propolis/ |
Dimethylsulfoxide extract |
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Different concentrations affect the growth of the tested bacteria | [ |
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Italy | Mediterranean propolis/ |
PEE |
|
Complete suppression of the factor coagulase, reduction of lipase and prevention of biofilm formation of |
[ |
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Brazil | Red propolis/ |
PEE |
|
NanoHA matrix with red and green propolis which reduces bacterial growth and biofilm formation, the nanoHA with red propolis being the most efficient | [ |
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Poland | European propolis/ |
Coagulase-positive |
Inhibition of |
[ | |
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|
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PEE |
|
Brazilian propolis having bacteriostatic activity; Bulgarian propolis having bactericidal activity; both having similar synergetic effect when in combination with amoxicillin, ampicillin, and cephalexin | [ |
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Increase of bactericidal activity of macrophages | [ | |||
|
Both samples having antibacterial activity but no synergistic effects with ciprofloxacin, norfloxacin, and cotrimoxazole | [ | |||
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Turkey |
|
PWE |
|
Inhibition of tuberculosis infection in guinea-pigs since it promotes a decrease in necrosis formation and increase in granuloma formation | [ |
PEE |
|
Inhibition of Gram-negative bacteria growth | [ | ||
Purchased from Sigma Aldrich Co. | Characteristic of European propolis | CAPE |
|
Competitive inhibitor against |
[ |
Antifungal activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells | Effect/stimulus | References |
---|---|---|---|---|---|
Brazil | Green propolis/ |
PEE |
|
Inhibition of cell growth, |
[ |
Green propolis/ |
PEE |
|
Both samples which decrease cell growth, red PEE being more efficient than the green one | [ | |
Green propolis/ |
PEE, PWE, matricial microparticles, and soluble dry extract |
|
PEE being the most potent in inhibiting cell growth followed by propolis soluble dry extract, propolis matricial microparticles, and PWE |
[ | |
Green propolis/ |
PEE, gels, and cream obtained from the extract |
|
Induction of cell death in |
[ | |
Green propolis/ |
PEE |
|
Inhibiting biofilm formation by |
[ | |
Red propolis/ |
|
5 |
Active against fluconazole resistant |
[ | |
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France | European propolis/ |
PEE, PWE, methanolic extract, and dichloromethane extract |
|
Antifungal activity against |
[ |
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Brazil | Green propolis/ |
PEE |
|
Increase of fungicidal activity of macrophages against |
[ |
Bulgaria | Mediterranean propolis/ |
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Czech Republic | European propolis/ |
Dimethyl sulfoxide extract |
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Affecting the growth of the tested bacteria in different ways by different concentrations | [ |
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Portugal (Bragança and Leiria) | European propolis/ |
PEE |
|
Plant extracts not exhibiting relevant antifungal activity, but in general both propolis samples affecting the fungal growth | [ |
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Poland | European propolis/ |
PEE | 20 isolated |
Inhibition of fungal growth | [ |
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Iran | European propolis/ |
PEE |
|
Decrease of |
[ |
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Brazil | Green propolis/ |
PEE and propolis microparticles | 89 yeast strains from vaginal exudates of the vulvovaginal candidiasis patients: 58 |
Inhibition of all yeasts growth by ethanol extract and propolis microparticles, with small variation, independent of the species of yeast | [ |
Argentina | Tropical region propolis |
PEE | Xylophagous ( |
Inhibition of fungal growth | [ |
Spain (Basque Country) | European propolis/ |
PEE and propylene glycol extracts |
|
Inhibition of fungal growth | [ |
Propolis effect against several bacterial strains has evaluated [
Mirzoeva et al. [
It has been suggested that the combination of propolis with other antibiotics would allow dose reduction of selected antibiotics, thus potentiating their effect. The antibacterial activity of Italian PEE in some clinically isolated Gram-positive strains, as well as the synergetic effect with some antibiotics, was assessed by Scazzocchio et al. [
Recently, the suitability of nanohydroxyapatite- (nanoHA-) based surfaces containing two Brazilian PEE (green and red ones) to prevent
Diverse studies show that as the composition of propolis varies from region to region, the antibacterial activity also displays some variations [
Antifungal activity is also influenced by the chemical variation of propolis [
Recently, Falcão et al. [
Brazilian PEE was proved to be active against several
Recognition of the hallmarks of cancer affects the search and development of new methods and therapeutic agents with a sufficiently large therapeutic window to kill tumour cells while sparing normal cells. In the last years, the natural product propolis has attracted a growing interest by a large number of researchers since it contains a variety of phytochemical compounds that may act through multiple pathways to reduce the development and other malignant characteristics of cancer cells.
Recently, several
Antitumoral activity of propolis and its chemical constituents.
Origin | Propolis type/plant source | Type of extract/isolated compound(s) | Species/cells | Effect | References |
---|---|---|---|---|---|
Thailand | Propolis from stingless bee |
Hexane extract | Colon (SW620), breast (BT474), hepatic (Hep-G2), lung (Chago), and stomach (Kato-III) cells |
High antiproliferative activity against the five cancer cell lines and low cytotoxic activity on the normal cell lines | [ |
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Poland | European propolis/ |
PEE | Human malignant melanoma cell line Me45; colorectal cancer cell line HCT 116 | Inhibition of cell growth and reduction of cell size of the tested cancer cells | [ |
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Synthesized | Characteristic of propolis from the Pacific region, Thailand, Africa, Australia, and Brazil | Prenylated flavanones | Prostate cancer cell lines PC-3 and DU-145 |
Induction of a more potent cytotoxicity against the PC-3 cell line than 5-flurouracil; induction of apoptosis | [ |
Characteristic of European propolis | CAPE | C6 cell line established from a glioma generated by intravenous exposure of male Wistar rats to N-nitrosomethylurea BALB/c-nu mice | Inhibition of C6 glioma cells growth; increase in the percentage of cells in the G0/G1 phase, and decrease in the protein level of hyperphosphorylated pRb; increase in cyclin dependent kinase inhibitors p21, p27, and p16; decrease in tumor growth in xenografts, reduction of the number of mitotic cells and proliferating cell nuclear antigen- (PCNA-) positive cells in C6 glioma | [ | |
HL-60 cell line | Induction of apoptosis by activation of caspase-3, downregulation of Bcl-2, and upregulation of Bax | [ | |||
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Brazil | Characteristic of Brazilian propolis | Drupanin, baccharin ((E)-3-prenyl-4-(2,3-dihydrocinnamoyloxy) cinnamic acid) and artepillin C (isolated from PEEs of propolis) | Human leukemia cell line HL-60, colon cancer cell line SW480 | Inhibition of cells growth; promotion of morphological changes and nucleosomal DNA fragmentation (artepillin C > baccharin > drupanin) | [ |
Red propolis/ |
Methanolic extract | Human pancreatic cancer cells (PANC-1) | Killing 100% of PANC-1 cells in the nutrient-deprived condition | [ | |
Green propolis/ |
PEE | DU145 and PC-3 cell lines, telomerase-immortalized primary human prostate cancer-derived cell (RC-58T/h/SA#4), and primary human prostate epithelial cells (PrEC) | Inhibition of human prostate cancer cells proliferation by regulating the protein expression of cyclin D1, B1 and cyclin dependent kinase (CDK), p21 | [ | |
Green propolis/ |
Baccharin, beturetol, kaempferide, isosakuranetin, and drupanin (isolated from PEE) | Human embryonic kidney 293 (HEK293) cell, HCT116 cell line | Inhibition of HIF-1 |
[ | |
Green propolis/ |
PEE | HUVECs cells | Induction of apoptosis in tube-forming endothelial cells through the inactivation of the survival signal ERK1/2 and by the activation of caspase-3 | [ | |
Green propolis/ |
PWE | Female Wistar rats | Inhibition of angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine- (BBN-) induced rat bladder cancer | [ | |
Red propolis/ |
PEE | Human immortalized endothelial-like cell line EA.hy926, renal cell carcinoma cell line RCC4, and mouse embryonic stem cell line CGR | Reduction of migration and sprouting of endothelial cells and attenuation of new blood vessels formation; decrease in the differentiation of embryonic stem cells into CD31 positive cells; decrease in HIF1- |
[ | |
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Brazil | Green propolis/ |
PEE | Human umbilical vein endothelial cells (HUVECs), NF1-deficient MPNST (S-462), and NF2-deficient schwannoma (HEI-193) cell lines |
Blocking PAK1 signaling selectively, without affecting AKT; suppressing almost completely the growth of human neurofibromatosis tumor xenografts in mice |
[ |
Synthesized | Characteristic of Brazilian |
Artepillin C | |||
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Brazil | Green propolis/ |
PEE | HUVECs |
Reduction of the number of newly formed vessels |
[ |
Purchased: Wako Pure Chemicals Industries (Osaka, Japan) | Characteristic of Brazilian propolis | Artepillin C | |||
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Brazil | Green propolis/ |
PEE | LNCaP cell line | Sensitizing TRAIL-resistant LNCaP cells to TRAIL-induced apoptosis |
[ |
Purchased: Alexis Biochemicals (San Diego, CA, USA) | Characteristic of Brazilian propolis | Quercetin, kaempferol, and | |||
Purchased: Wako Pure Chemicals (Osaka, Japan) | Artepillin C | ||||
Brazil | Red propolis/ |
PEE | MCF-7 cell line | Reducing cell viability through induction of mitochondrial dysfunction, caspase-3 activity, and DNA fragmentation and increase in expression of CCAAT/enhancer-binding protein homologous protein (CHOP) |
[ |
Purchased: Api Co. Ltd., Gifu, Japan | Characteristic of European propolis | CAPE | |||
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Purchased: Sigma Aldrich Co. | Characteristic of European propolis | CAPE | LNCaP 104-S, DU-145, and PC-3 cell lines |
Suppressing the growth of LNCaP, DU-145, and PC-3 and inhibiting the tumor growth of LNCaP xenografts, possible inhibition of p70S6K and some Akt signaling networks | [ |
PC-3 cell line | Suppressing proliferation, colony formation, and cell cycle progression, decrease in protein expression of cyclin D1, cyclin E, SKP2, c-Myc, Akt1, Akt2, Akt3, total Akt, mTOR, and Bcl-2, Rb, as well as phosphorylation of Rb, ERK1/2, Akt, mTOR, GSK3a, GSK3b, and PDK1, and increase in KLF6 and p21Cip1 protein expression | [ | |||
Breast cell lines MDA-MB-231, MCF-7, MCF-10A, and MCF-12A Bovine capillary endothelial (BCE) cells |
Inhibition of |
[ | |||
Breast cancer cell lines MDA-MB-231, MCF-7, and SKBR3 | Promotion of an accumulation of acetylated histone proteins in MCF-7 (ER+) and MDA-MB-231 (ER−/PR−/Her2−); decrease of ER and PR in MCF-7 cells and upregulation of ER and decrease of EGFR in MDA-MB-231 cells; reduction of Her2 protein in SKBR3 (Her2+) cells | [ | |||
Human oral squamous cell carcinoma TW2.6 | Suppression of cell proliferation and colony formation; decrease of G1 phase cell population, increase of G2/M phase cell population; induction of apoptosis; decrease of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3 |
[ | |||
MDA-MB-231 cell line | Inhibition of cancer stem cells self-renewal, progenitor formation, and clonal growth and decrease of CD44 levels | [ | |||
Human hepatocellular carcinoma cell line SK-Hep1 | Suppression of the adhesion and invasion potential of the cells by inhibiting completely the expression of MMP-2 and metalloproteinase-9 (MMP-9) and the NF- |
[ | |||
Human fibrosarcoma cell line HT1080 | Decrease of MMP and tissue inhibitor metalloproteinase-2 (TIMP-2) mRNA levels; downregulation of MMP-2 and MMP-9 expression; inhibition of MMP-2 activity; decrease of invasion, motility, cell migration, and colony formation | [ | |||
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Turkey | Mediterranean propolis |
PEE | MCF-7 cell line | Increase of apoptosis through the caspase pathway | [ |
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Iraq | European propolis/ |
PWE | HL-60 cell line, colon cancer cell HCT-116 |
Inhibition of HL-60 cells proliferation and induction of apoptosis by downregulating Bcl-2 protein and upregulating Bax; inhibition of HCT-116 cells colony formation potential and promotion of necrotic changes; decrease of mitotic cells and increase of p53 and Ki-67 expression in HCT-116 tumor-bearing mice | [ |
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Iran | European propolis/ |
PEE | Male Wistar rats | Decrease of tumour incidence, number of lesions, structural abnormalities, and beta-catenin and induction of proapoptotic Bax expression and reduction of antiapoptotic Bcl-2 expression | [ |
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Provided by Wako Pure Chemicals (Osaka, Japan) | Characteristic of Brazilian propolis | Artepillin C | LNCaP cell line | Induction of caspase-8 and caspase-3 activation and disruption of mitochondrial membrane potential by a cotreatment with TRAIL and artepillin C | [ |
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Purchased | Characteristic of European propolis | CAPE | MCF-7 cell line | Induction of apoptosis via Fas signal; induction of Bax protein and activation of caspases and MAPK family proteins p38 and JNK | [ |
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Purchased: Calbiochem (San Diego, CA, USA) | Characteristic of European propolis | CAPE | Lymphoblastoid cell line PL104 | Induction of apoptosis through phosphatidylserine (PS) exposure and nuclear fragmentation |
[ |
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China; | European propolis/ |
PEE | HUVECs | Inhibition of VEGF expression |
[ |
Purchased: Api Co. Ltd. (Gifu, Japan) | Characteristic of European propolis | CAPE | |||
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Korea; | European propolis/ |
PEE | Fertilized chicken eggs |
Inhibition of angiogenesis in chick embryo chorioallantoic membrane and inhibition of CPAE cells proliferation |
[ |
Synthesized | Characteristic of European propolis | CAPE | |||
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Portugal: (Serra de Bornes and Fundão); | European propolis/ |
Methanolic extract | Normal and cancerous renal cells derived from human renal cell carcinoma patients, human renal carcinoma cell line A-498 | Inhibition tumor cells growth exhibiting selective toxicity against malignant cells compared to normal cells | [ |
(Anga do Heroísmo, Azores) | PEE and hexane, chloroform, and residual ethanol extract fractions obtained from the PEE | Human colorectal adenocarcinoma cell line HCT-15 | All the samples exhibiting cytotoxic effect against tumor cells; chloroform fraction decreasing cell viability, promoting cell death, and disturbing tumor cell glycolytic metabolism | [ |
Some researchers showed the effect of different types of propolis and its constituents on cancer cell growth, proliferation, and apoptosis. The hexane extract of propolis from Thailand, collected by the stingless bee
Although propolis containing CAPE is different from those with artepillin C, it is possible to obtain a similar inhibitory effect from both types. The effect of CAPE on different cancer cell lines was analysed and many of its effects have been shown to be mediated through inhibition of NF-
As previously said, propolis can also act by decreasing the cancer stem cell population. Using the putative CD44 (+)/CD24 (−/low) breast cancer stem cells able to generate mammospheres from single cells, Omene et al. [
Concerning cell death, some
It has been known that cancer microenvironment is very important for carcinogenesis and it consists of stromal, endothelial, immune, and cancer cells. Natural products, like propolis and their constituents, have been shown to interfere with this symbiosis. It was demonstrated by Lee et al. [
Angiogenesis has a crucial role in tumour growth due to the requirement of oxygen and nutrients to sustain rapid uncontrolled proliferation and metastization. Both tumour and stromal cells can secrete proangiogenic factors that stimulate the formation and maintenance of new vessels, such as vascular endothelial growth factor (VEGF) [
The first study on the antitumor activity of Portuguese propolis was only performed in 2010. Using normal and cancerous renal cells derived from human renal cell carcinoma (RCC) patients, in addition to A-498 cell line, Valente et al. [
From ancient to modern times, herbs and other plant products have been widely used as medicinal agents, first in folk medicine and other activities in many parts of the world and later developed and improved on a scientific basis into drugs that are used in the health system. Propolis is one of the few natural products that has maintained its popularity over a long period of time. As reviewed here, propolis contains a broad spectrum of compounds that may be useful in the treatment of different pathological conditions. In fact there is much literature that deals with the
Drug discovery does not consist only of the isolation of bioactive lead compounds from the natural sources. In fact, this process continues outside the academic laboratories through preclinical studies followed by clinical trials. Thus, despite the
Caffeic acid phenethyl ester
Propolis ethanol extract
Propolis water extract
Reactive nitrogen species
Reactive oxygen species
Vascular endothelial growth factor.
The authors declare that there is no conflict of interests regarding the publication of this paper.