Plant Profiler

Propolis (Propolis)


Propolis (Propolis) Image
Synonyms / Common Names / Related Terms
Apis mellifera L., bee glue, bee propolis, bee putty, Bienenharz (German), Brazilian green propolis, Brazilian propolis, Bulgarian propolis, caffeic acid phenethyl ester, CAPE, cera alba, chizukit, cinnamic acid, flavonoids, galangin, Greek propolis, hive dross, Propolin H, propolis balsam, propolis resin, propolis wax, propolisina (Spanish), Russian penicillin, Taiwanese propolis, terpenes, WSDP.

Combination product example: Chizukit (preparation containing echinacea, propolis, and vitamin C).



Mechanism of Action

Pharmacology:

  • Constituents: Propolis composition is considered to be highly variable and dependent on the plant species from which it is collected as well as the season and geographical location in which it is harvested.1,16 Propolis extracts have been found to contain amino acids, phenolic acids, phenolic acid esters, flavonoids, cinnamic acid, cumaric acid, terpenes, hesperatin, nicotinic acid, and caffeic acid.19,8,30,1,20,31 Propolis also contains resins, balsams, essential oils, vitamins, minerals and pollen1, propolin H24, polyphenols, phenolic aldehydes, sequiterpene quinines, coumarins, steroids16, and phenylpropanoids (PPs)20. Propolis of Brazilian origin is reported to be composed mainly of artepillin C and its constituents have been found to be different from those of propolis of European origin.32 Two prenylflavanones, propolin A and propolin B, have been isolated and characterized from Taiwanese propolis.33
  • Anti-inflammatory effects: There is preliminary in vitro and in vivo evidence that propolis suppresses the lipoxygenase pathway of arachidonic acid metabolism and decreases the synthesis of prostaglandins and leukotrienes involved in inflammation.22,21,19 Propolis has also demonstrated free radical-scavenging properties, and to a lesser extent, activity against the generation of superoxides.34,35,5 Propolis may inhibit cellular apoptosis via effects on glutathione (GSH) and TNF-kappa B in macrophages.36,6 Anticomplement activities of lysine complexes of propolis' phenolic constituents have been demonstrated in vitro.37 In a prospective, open human trial in 10 healthy subjects, Propolis XNP 500mg over 13 days did not significantly alter plasma cytokine levels.38 Topical application of a 3%-7% propolis extract may be effective in inhibiting carrageenan-induced rat hind paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the anti-inflammatory effect observed.2 The anti-inflammatory effect of a standard ethanol extract G1 from Brazilian green propolis may be a due to inhibition of iNOS gene expression, through interference with NF-kappaB sites in the iNOS promoter.3
  • Antimicrobial properties: Propolis contains flavonoids including pinocembrin, galangin, pinobanksin, and pinobanksin-3-acetate, which are thought to be responsible for antimicrobial effects. Laboratory studies have shown antibacterial effects against Enterococcus faecalis 39, Clostridium, Bacteroides and Propionibacterium species14, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes4, and Helicobacter pylori strains23. Propolis extracts that contain the constituents pinocembrin and galangin have been shown to inhibit the growth of Streptococcus mutans, an organism that causes dental caries. In vitro studies have shown propolis to inhibit bacterial growth by disrupting the cell wall, the cytoplasmic membrane, and the cytoplasm, causing a partial bacteriolysis and inhibition of cellular protein synthesis40,41 Other in vitro experiments have demonstrated activity against Gram-positive bacteria.42,43,44,45,46,47 However, in an experiment designed to measure induction of resistance, Scheller et al. found that out of 62 strains of Streptococcus aureus isolated from various sources, approximately 90% showed either initial reduced sensitivity or complete resistance to propolis, regardless of the concentration of the ethanol extract of propolis used.46 The in vitro antiviral activity of propolis has been attributed to a synergistic action of both flavonoid and flavanol components in propolis.19 Studies evaluating the efficacy of isolated constituents have demonstrated minimal effectiveness compared to the natural compound.48 Propolis has also been found to inhibit oral candidiasis.49 In an in vitro study, an ethanolic extract of propolis was shown to inhibit growth and adherence of Giardia duodenalis trophozoites.50 The level of inhibition varied according to the extract concentration and incubation times. The highest reduction of parasite growth was observed in cultures exposed to 125, 250 and 500mcg/mL of propolis, in all incubation periods (24, 48, 72, and 96 h). Growth reduction by 50% was observed in 125mcg/mL propolis-treated cultures, while the concentrations of 250 and 500mcg/mL were able to inhibit growth by more than 60%. Propolis also promoted the detachment of trophozoites. Light microscope observations revealed changes of the pear-shaped aspect of the cell and reduction of flagellar beating frequency in the great part of the trophozoites. In vitro, propolis has been shown to be cytotoxic for Candida albicans; though it did appear to affect epithelial cell adhesion, propolis appeared to inhibit other virulence factors of Candida albicans such as yeast-mycelial conversion (Y-M) and phospholipase activity in a dose-dependent manner.10 Additional laboratory study confirmed that propolis extract showed antifungal activity against Candida parapsilosis, Candida tropicalis, and Candida albicans at a concentration of 5 x 10(-2)mg/mL of flavonoids; a concentration of 2 x 10(-2)mg/mL of flavonoids stimulated their cellular death.51 Additional in vitro studies have confirmed the antifungal effects of propolis as well.52
  • Antineoplastic properties: Numerous studies have been conducted investigating the antiproliferative effects of propolis. In vitro cytotoxicity against human fibrosarcoma, human lung carcinoma, and murine colon carcinoma cells has been demonstrated by propolis and attributed to its benzofuran derivatives.53,9,10,54 Other constituents such as artepillin C and diethyl ether have demonstrated cytostatic activity against myeloid cell lines.32,55,11 Significant results have been seen against T-cell lines.11 The propolis constituent galangin has been found to possess anti-genotoxic activity in vitro.56,34 Chilean propolis has been shown to produce antiproliferative properties, which are correlated with its chemical composition and expressed by its capacity to scavenge free radicals and to inhibit tumor cell growth.57 In an in vitro study, two prenylflavanones, propolin A and propolin B, isolated and characterized from Taiwanese propolis, induced cytotoxicity in human melanoma A2058 cells and showed a strong capability to scavenge free radicals.33 The findings suggest that propolin A and propolin B may activate a mitochondria-mediated apoptosis pathway. Furthermore, in an in vitro study, the compound 2-hydroxy-3-(1,1-dimethylallyl)acetophenone showed significant selective cytotoxic activity (IC50 < 9mcgg/mL).58 In another in vitro study, results suggested that chemotherapy based on resveratrol and propolis, alone or in combination with vinorelbine, may be a potentially useful tool for prostate cancer therapy. The authors concluded that the increase in cell cycle control and the modulation of HSPs expression reinforce this suggestion.59 Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been implicated in the regulation of cell growth and apoptosis, although the exact mechanism of this activity has not been elucidated.12 All-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL); however, the response is sometimes very slow.25 It is suggested that CAPE possesses the potential to enhance the efficiency of ATRA in the differentiation therapy of APL. In an in vitro study, results showed that the drastic activation of HO-1 gene by CAPE and caffeic acid ethyl ester (CAEE) is dependent upon their chemical structures, rather than the reductive activity of polyphenols.27 Furthermore, the effects of a propolis extract obtained by supercritical fluid extraction and CAPE on sensitivity to chemotherapeutic agents were examined in HeLa cells and resistant sublines.26 In HeLa cells, the sensitivity to paclitaxel and doxorubicin, substrates of MDR1, was unchanged in the presence of propolis. In HeLa/TXL cells, propolis increased sensitivity to these MDR1 substrates. The authors suggested that the extract inhibited the function of MDR1 and increased the sensitivity to MDR1 substrates in HeLa/TXL cells. In a cytotoxicity assay of CAPE in CT26 colon adenocarcinoma cells, a dose-dependent decrease in cell viability was observed, but no significant influence on the growth of human umbilical vein epithelial cells (HUVEC) was observed. A low concentration of CAPE (1.5mcg/mL) inhibited 52.7% of capillary-like tube formation in HUVEC culture on Matrigel. CAPE (6mcg/mL)-treated CT26 cells showed not only inhibited cell invasion by 47.8%, but also decreased the expression of matrix metalloproteinase (MMP)-2 and -9. Vascular endothelial growth factor (VEGF) production from CT26 cells was also inhibited by treatment with CAPE (6mcg/mL). Intraperitoneal injection of CAPE (10mg/kg per day) in BALB/c mice reduced the pulmonary metastatic capacity of CT26 cells accompanied with a decreased plasma VEGF level. CAPE treatment also prolonged the survival of mice implanted with CT26 cells. These results indicate that CAPE has potential as an antimetastatic agent.60 The antitumor activity of a water-soluble derivative of propolis, caffeic acid, caffeic acid phenethyl ester, and quercetin may be related to the immunomodulatory properties of the compounds, their cytotoxicity to tumor cells, and their capacity to induce apoptosis and necrosis.61 In an in vitro study, propolin H, isolated from propolis, was found to inhibit the proliferation of human lung carcinoma cell lines.24 These findings suggest that the induction of p21Waf1/Cip1 expression occurred through p53-dependent and independent pathways in propolin H-treated cells.
  • Antioxidant properties: Chilean propolis has been shown to produce antioxidant properties, which are correlated with its chemical composition and expressed by its capacity to scavenge free radicals and to inhibit tumor cell growth.57 Propolis has also been studied for antiradical properties to protect food from oxidation.62 Based on in vivo study, daily intake of powdered propolis extract may be time and gender related.63 For men, after the initial 15 days of propolis treatment, a 23.2% (p=0.005) decrease in concentration of malondialdehyde was observed. After 30 days of treatment, a statistically significant (p=0.010) 20.9% increase in superoxide dismutase activity and a change in some of the red blood cell parameters were detected. For the women test group, the propolis treatment did not induce a change in any of the measured parameters. It has also been suggested that the potential antioxidant and free radical scavenging properties of propolis may be due to the action of phenylpropanoid constituents.20
  • Antiplatelet effects: A laboratory study examined the inhibitory mechanisms of caffeic acid phenethyl ester (CAPE), derived from propolis, in platelet activation.8 CAPE (15 and 25mcM) was found to markedly inhibit platelet aggregation stimulated by collagen (2 mcg/mL). Since CAPE is involved in various inhibitory pathways of platelet aggregation, the authors concluded that propolis may be a potent antiplatelet agent.
  • Anti-viral effects: Propolis has been shown to contain compounds that prevent HIV-1 accessory protein Nef-mediated cell lysis and increase proliferation of CD4 cells in HIV-infected cultures.28
  • Epithelial repair: Topically, propolis has been reported to accelerate epithelial repair after tooth extraction in animal models.64
  • Fertility protective effects: In an in vitro study, a Chilean propolis ethanolic extract was able to protect human spermatozoa genomic DNA by damage induced by benzo[a]pyrene, hydrogen peroxide (H2O2), and hydrogen peroxide in combination with adenosine 5'-diphosphate (ADP) and ferrous sulfate (FeSO4).18 The propolis extract studied was shown to protect sperm membranes from oxidative attack, via reducing TBARS formation and LDH release. The authors concluded that the protective effect of propolis in human spermatozoa may be correlated with antioxidant capacity and suggested that propolis may protect against male infertility.
  • Immunomodulatory effects: In an animal study, the immunomodulatory actions of a water-soluble derivative of propolis (WSDP) and two components of propolis, caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) were investigated.7 Oral administration (50mg/kg) of WSDP, CA, and CAPE enhanced the weight and cellularity of the spleen (p<0.05, p<0.01) of treated mice. The response of spleen cells to polyclonal mitogens was also increased in mice treated with WSDP as compared to control (p<0.01); in contrast, the response of spleen cells of mice treated with CA were significantly suppressed (p<0.001). Antitumor activity of the propolis compounds tested may be due to immunomodulatory actions, specifically augmentation of non-specific antitumor resistance in mice via macrophage activation and production of soluble factors interfering with tumor cells. In immunocompetent mice infected with Giardia lamblia trophozoites, propolis as a prophylaxis showed a significant decrease in intensity of infection and a significant increase in IF-gamma serum level and increase in CD4+: CD8+T-cell ratio.17 The propolis treatment caused a highly significant decrease in trophozoite count than that obtained by metronidazole (MTZ) six days after infection; however, the efficacy was almost equal after 12 days. The mice treated with propolis alone showed a reversed CD4+: CD8+ T-lymphocyte ratio; the authors noted that the strong immune-enhancing effect resulted in an undesirable increase in inflammatory response at the intestinal level. The combined propolis and metronidazole (MTZ) therapy showed a stronger efficacy in reducing the parasite count than that gained by each agent alone and caused an immunological balance as shown by the T-lymphocyte profile.
  • Osteoporosis preventative effects: Propolis has been reported to contain trace amounts of ipriflavone, an isoflavone with purported efficacy in the prevention of osteoporosis. However, it is not clear if the presence of ipriflavone in propolis is of clinical significance.
  • Periodontal effects: In an in vitro study, results showed that 10% propolis solution was an effective storage medium for the maintenance of periodontal ligament (PDL) cell viability of avulsed teeth.15 In an in vitro study, propolis caused some reduction in malodor production from the incubated whole saliva.65
  • Radioprotective effects: In animal studies, the radioprotector effect of propolis has been attributed to its free-radical scavenging properties.13 In an in vitro study examining the protective properties of propolis extract against DNA damage induced by gamma irradiation, a decrease in the radiation-induced chromosome aberrations has been observed to be higher than 50% for all the doses.

Pharmacodynamics/Kinetics:

  • Literature review reveals scant evidence regarding the absorption, distribution, metabolism, or elimination of propolis either topically or orally. The flavonoids, many of which are found in propolis, are known to exhibit a wide range of solubility. In natural propolis, flavonoids exist as glycosides. Animal studies have found that byproducts of flavonoid metabolism do not accumulate in the body and are renally excreted.66
  • The in vitro biochemical stability of caffeic acid phenethyl ester in rat and human plasma was investigated and compared with the stability of other caffeic acid esters (chlorogenic acid and rosmarinic acid).67 The results suggested that caffeic acid phenethyl ester is hydrolyzed also in vivo to caffeic acid as the major metabolite and that its biological activities should be more properly assayed and compared with those of caffeic acid, its bioactive hydrolysis product. The authors concluded that alcohols should be carefully used in vivo as solvents for caffeic acid phenethyl ester because they may give rise to new bioactive caffeic acid esters.
  • In samples of whole blood of male Wistar rats incubated in sequence with an aqueous propolis extract at different concentrations, stannous chloride and 99mTc, as sodium pertechnetate, the aqueous propolis extract significantly decreased the percentage of incorporated radioactivity (%ATI) in plasma proteins at the higher concentration studied.29 The results suggested that at high concentration, the constituents of propolis extracts may alter the labeling of plasma proteins competing with same binding sites of the 99mTc on the plasma proteins or acting as antioxidant compounds.
  • Pharmacodynamics: In an in vitro study, prenyl compounds from propolis were tested for their cytotoxicity toward a diverse panel of cultured human tumor cell lines.58 The compound 2-hydroxy-3-(1,1-dimethylallyl)acetophenone showed significant selective cytotoxic activity (IC50 <9mcg/mL).
  • In an in vitro study, a propolis extract showed antifungal activity against 67 yeasts (Candida parapsilosis 35%, C. tropicalis 23%, C. albicans 13%, and other species 29%) isolated from onychomycosis in patients: the concentration capable of inhibiting the all of the yeasts was 5 x 10(-2)mg/mL of flavonoids, and 2 x 10(-2)mg/mL of flavonoids stimulated their cellular death. Trichosporon sp. were the most sensitive species, showing MIC50 and MIC90 of 1.25 x 10(-2)mg/mL of flavonoids, and C. tropicalis was the most resistant, with CFM50 of 5 x 10(-2)mg/mL of flavonoids and MFC90 of 10 x 10(-2)mg/mL.
  • Caffeic acid phenylethyl ester (CAPE), a component of propolis, as well as other derivatives of caffeic acid, up-regulated the expression of reporter gene for retinoic acid receptors (RARs).68

References

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