Metabolic products of European-type propolis. Synthesis and analysis of glucuronides and sulfates.

ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee-derived product used since antiquity for its general health-giving properties and is especially noted for its anti-bacterial activity. In more recent times, propolis has been employed against more specific targets such as antiproliferative effects vs cancer cells, wound healing and type-2 diabetes. AIM OF THE STUDY: European (poplar)-type propolis from New Zealand contains a number of hydroxy cinnamic acid esters and a set of aglycone flavonoid compounds, mainly chrysin, galangin, pinocembrin and pinobanksin. Propolis is usually taken orally and propolis metabolites quickly appear in the plasma of the ingested. In this work we aimed to identify the major flavonoid plasma metabolites by direct analysis of the plasma. MATERIALS AND METHODS: After consumption of a large dose of propolis in a single sitting, blood samples were taken and analysed using LCMS/MS. The major flavonoid metabolites identified were also synthesised using chemical (sulfates) or enzymatic methods (glucuronides). RESULTS: Both the sulfate and glucuronide conjugates of the four major propolis flavonoids are readily detected in human plasma after propolis ingestion. Preparation of the sulfates and glucuronides of the four major flavonoids allowed the relative proportions of the various metabolites to be determined. Although the sulfates are seen as large peaks in the LCMS/MS, the glucuronides are the dominant conjugate species. CONCLUSIONS: This study shows most of the flavonoids in the plasma are present as 7-O-glucuronides with only galangin showing some di-glucuronidation (3,7-O-diglucuronide). No evidence was found for hydroxy cinnamic acid type metabolites in the plasma samples.

Pharmacokinetics and metabolism of cinnamic acid derivatives and flavonoids after oral administration of Brazilian green propolis in humans.

Brazilian green propolis (BGP) has chemical compounds from botanical origin that are mainly cinnamic acid derivatives (artepillin C, baccharin, and drupanin) and flavonoids (kaempferide and 6-methoxykaempferide). These compounds are expected to play an important role in the pharmacological activities of BGP. However, there is little known about the pharmacokinetics and metabolism of these compounds after oral administration of BGP. The aim of this study is to investigate the pharmacokinetics and metabolism of BGP components in humans. Twelve volunteers received 3 capsules containing 360 mg of BGP ethanol extract powder. Plasma samples were collected before and up to 24 h after the intake of BGP capsules. The collected plasma samples with or without hydrolysis by the deconjugating enzyme were analyzed by LC/MS/MS. After enzymatic hydrolysis, the Cmax values of artepillin C and drupanin, which were detected mainly in plasma after ingestion of BGP capsules, were 1255 ± 517 and 2893 ± 711 nM, respectively, of which 89.3% and 88.2% were found to be the phenolic glucuronide conjugate. This is the first time that the pharmacokinetics of the BGP components of human metabolites have been reported. Our results could provide useful information for the design and interpretation of studies to investigate the mechanisms and pharmacological effects of BGP.

Inhibitory effect of Brazilian red propolis on planktonic and biofilm forms of Clostridioides difficile.

Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacillus which is the leading cause of health-care-associated infective diarrhea. The rising incidence of antibiotic resistance in pathogens such as C. difficile makes researches on alternative antibacterial products very important, especially those exploring natural products like propolis. Brazilian Red Propolis, found in the Northeast region of Brazil, is composed by products from regional plants that have the antimicrobial properties. This study aimed to evaluate the in vitro activity of Brazilian Red Propolis (BRP) against C. difficile strains in planktonic and biofilm forms. The susceptibility of four strains of C. difficile to BRP was analyzed by broth microdilution method and vancomycin was included as control drug. BRP-exposed C. difficile cells were evaluated by scanning electron microscopy (SEM). Then, the effects of BRP on growing and mature C. difficile biofilms were also evaluated. BRP minimum inhibitory concentration was 625 µg/mL against all tested strains, while vancomycin MIC range was 0.5-2 µg/mL. SEM showed the loss of homogeneity in bacterial cell wall and cell fragmentation, after BRP-exposure. BRP, at MIC, reduced (P < 0.05) the biomass, matrix proteins and matrix carbohydrates of growing biofilms, and, at 8xMIC, reduced (P < 0.05) the biomass and matrix proteins of mature biofilms. The present study demonstrated that BRP inhibits planktonic growth, damages cell wall, decreases biofilm growth and harms mature biofilms of C. difficile.

Design and in vitro antibiofilm activity of propolis diffusion-controlled biopolymers.

In this study, a novel pH-sensitive hydrogel beads that is based on gelatin/sodium alginate/chitosan (GEL/SA/CS) loaded with propolis ethanolic extracts (PE) were synthesized. The swelling behavior of GEL/SA/CS hydrogel beads was studied in different pH solutions and compared with unloaded CS (GEL/SA) hydrogel beads. The in vitro release studies have been revealed using four different pH (1.3, 5.0, 6.0, and 6.8), a saliva environment (pH 6.8), a simulated gastric fluid (SGF) (pH 1.3), and a simulated intestinal fluid (SIF) (pH 6.8) to simulate the physiological conditions in gastrointestinal (GI) tract. Propolis-loaded hydrogel beads were found to be stable at pH 1.3, 5.0, 6.0, simulated saliva, SGF, and SIF mediums, whereas the beads lose their stability at pH 6.8 buffer solution. Tested microorganisms displayed greater sensitivity to PE-loaded hydrogel beads compared with pure propolis. Contrary to antimicrobial activity results, antibiofilm activity results of PE-loaded GEL/SA and GEL/SA/CS hydrogel beads were found at low levels. According to the obtained results, the propolis-loaded GEL/SA/CS hydrogel beads synthesized within this study can be used in the treatment of GI tract diseases such as oral mucositis, gastric ulcer, ulcerative colitis, and GI cancer, as controlled releasing carriers of propolis.

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19.

The present work aimed to develop an optimized liposomal formulation for enhancing the anti-viral activity of propolis against COVID-19. Docking studies were performed for certain components of Egyptian Propolis using Avigan, Hydroxychloroquine and Remdesivir as standard antivirals against both COVID-19 3CL-protease and S1 spike protein. Response surface methodology and modified injection method were implemented to maximize the entrapment efficiency and release of the liposomal formulation. The optimized formulation parameters were as follow: LMC of 60 mM, CH% of 20% and DL of 5 mg/ml. At those values the E.E% and released % were 70.112% and 81.801%, respectively with nanosized particles (117 ± 11 nm). Docking studies revealed that Rutin and Caffeic acid phenethyl ester showed the highest affinity to both targets. Results showed a significant inhibitory effect of the optimized liposomal formula of Propolis against COVID-3CL protease (IC50 = 1.183 ± 0.06) compared with the Egyptian propolis extract (IC50 = 2.452 ± 0.11), P < 0.001. Interestingly, the inhibition of viral replication of COVID-19 determined by RT_PCR has been significantly enhanced via encapsulation of propolis extract within the liposomal formulation (P < 0.0001) and was comparable to the viral inhibitory effect of the potent antiviral (remdesivir). These findings identified the potential of propolis liposomes as a promising treatment approach against COVID-19.

Application of an Inter-Species Extrapolation Method for the Prediction of Drug Interactions between Propolis and Duloxetine in Humans.

Duloxetine (DLX) is a potent drug investigated for the treatment of depression and urinary incontinence. DLX is extensively metabolized in the liver by two P450 isozymes, CYP2D6 and CYP1A2. Propolis (PPL) is one of the popular functional foods known to have effects on activities of CYPs, including CYP1A2. Due to the high probability of using DLX and PPL simultaneously, the present study was designed to investigate the potent effect of PPL on pharmacokinetics (PKs) of DLX after co-administration in humans. A PK study was first conducted in 18 rats (n = 6/group), in which the plasma concentration of DLX and its major metabolite 4-hydroxy duloxetine (4-HD) with or without administration of PPL was recorded. Population PKs and potential effects of PPL were then analyzed using NONMEM software. Lastly, these results were extrapolated from rats to humans using the allometric scaling and the liver blood flow method. PPL (15,000 mg/day) exerts a statistically significant increase in DLX exposures at steady state, with a 20.2% and 24.6% increase in DLX C m a x , s s and the same 28.0% increase in DLX A U C s s when DLX (40 or 60 mg) was administered once or twice daily, respectively. In conclusion, safety issues are required to be attended to when individuals simultaneously use DLX and PPL at high doses, and the possibility of interactions between DLX and PPL might be noted.

Bioavailability and In Vivo Antioxidant Activity of a Standardized Polyphenol Mixture Extracted from Brown Propolis.

Several lines of evidence demonstrate the antioxidant, anti-inflammatory and antimicrobial activities of propolis, mostly ascribed to its polyphenol content. However, little is known regarding the bioavailability of propolis in acute and prolonged settings of oral administration. In this study, we first determined the content of the main polyphenols in a brown propolis extract obtained using a patented extraction method (Multi Dinamic Extraction-M.E.D.) by RP-HPLC-UV-PDA-MSn analysis, followed by the bioavailability of galangin and chrysin, the most abundant polyphenols in the mixture (7.8% and 7.5% respectively), following acute (single bolus of 500 mg/kg containing about 3.65 mg of the polyphenol mixture) and prolonged (100, 250 and 500 mg/kg body for 30 days) oral administration in 30 male 8 weeks old C57BL/6 wild-type mice. In the acute setting, blood was taken at 30 s and 5, 10, 15, 20, 25, 30, 45, 60 and 120 min following the oral bolus. In the prolonged setting, blood samples were obtained after 10, 20 or 30 days of administration. At the end of treatment, expression of antioxidant enzymes (superoxyde dismutase, SOD-1; catalase, CAT; glutathione peroxidase, GSS) was evaluated in liver tissue. Following both acute and prolonged administration, neither galangin nor chrysin were detectable in the plasma of mice, whereas the glucuronide metabolite of galangine was detectable 5 min after acute administration. At the end of the prolonged treatment SOD-1 was found to have increased significantly, unlike CAT and GSS. Overall, these data suggest that oral administration of whole brown propolis extract is followed by rapid absorption and metabolization of galangin followed by adaptations of the antioxidant first line defense system.

Propolis-based niosomes as oromuco-adhesive films: A randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers.

Oromuco-adhesive films for buccal delivery of Propolis extract (PPE) entrapped in niosomes, were prepared to treat oral recurrent aphthous ulcer (RAU). PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and in vitro release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7 ± 0.15 µg quercetin equivalents and phenolic content of 180.8 ± 0.11 µg gallic acid equivalents/mg. Multilamellar niosomes of 176-333 nm displayed entrapment efficiency of 91 ± 0.48%, PDI of 0.676 and zeta potential of -4.99. In vitro release after 8 h from niosomal dispersion and films were 64.05% and 29.09 ± 0.13% respectively. Clinical results revealed duration of film adherence from 2-4 h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4-5 h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.

Chitosan-based nano-in-microparticle carriers for enhanced oral delivery and anticancer activity of propolis.

This study reports a promising approach to enhance the oral delivery of propolis, improve its aqueous solubility and bioavailability, and allow its controlled release as well as enhancing its anticancer activity. Propolis was standardized then its solubility was improved via formulation into optimized solid dispersion (SD) matrices, and its release was controlled through incorporation into nanoparticles (NPs) of optimized composition followed by further inclusion into chitosan (Cs) microparticles. The anticancer activity of the newly developed propolis-loaded nano-in-microparticles (NIMs) was evaluated against human liver cancer (HepG2) and human colorectal cancer (HCT 116) cells. The prepared SDs, NPs and NIMs were characterized using SEM, TEM, DLS, FTIR, DSC and UV-vis spectrophotometry. The therapeutic efficiency of formulated propolis was bio-assessed via cytotoxicity measurements, mitochondrial dysfunction, apoptosis-induced cell death and cell cycle arrest. The results demonstrated a considerable enhancement in propolis solubility with a controlled release profile in different GIT environments. In-vitro cytotoxicity studies showed that the propolis-loaded NIMs induce more cytotoxic effect on HepG2 cells than HCT-116 cells and mediated three-fold higher therapeutic efficiency than free propolis. The apoptosis assay indicated that the propolis-loaded NIMs induce apoptosis of HepG2 cells and significantly decrease their number in the proliferative G0/G1, S and G2/M phases.

Synergistic effect of anti-platelet and anti-inflammation of drug-coated Co-Cr substrates for prevention of initial in-stent restenosis.

Antiplatelet and antithrombotic therapies are systematically considered to prevent restenosis following coronary stent implantation. Currently, patients receiving medicated stents are prescribed to orally take anticoagulants and antiplatelet drugs such as aspirin (ASP) and prasugrel (PRAS). Propolis (PROP) known as a natural organic compound was recently evaluated for its antiplatelet activity, antibiotics and immunomodulatory activities. In this study, antiplatelet drug-coated Co-Cr substrates were prepared with biodegradable poly(d,l-lactide) (PDLLA) containing ASP, PRA, or PROP using electrospray and the blood compatibility of the different substrates was investigated by measuring protein adsorption and platelet adhesion. In addition, the anti-inflammatory properties of the modified Co-Cr surfaces were assessed by measuring IL-8 and IL-6 expression levels in human endothelial cell cultures. Drug-coated surfaces were found to resist the adsorption of fibrinogen when compared to bare Co-Cr or PDLLA-coated Co-Cr. Interestingly, ASP- and PROP-containing substrates not only showed reduced adhesion of platelets and delayed coagulation time, but also drastically reduced the expression level of IL-8 and IL-6. Such results are supported that ASP- or PROP-coated Co-Cr can be potentially used as a stent material to mitigate early stage of restenosis. The developed coating materials might be an interesting alternative to systemic anticoagulant therapies prescribed after stent implantation.

Pharmaceutical films made from the waste material from the preparation of propolis extracts: development and characterization

abstract This study investigated the development and characterized the physicochemical properties of films obtained from by-products (BP) from the preparation of propolis extracts. Films were produced in the presence and absence of a polymeric adjuvant (gelatin or ethylcellulose) and propylene glycol by a solvent casting method. Density, surface topography by scanning electron microscopy, mechanical properties (folding endurance, tensile strength and percentage elongation), water vapour permeability (WVP), moisture uptake capacity, thermogravimetry, differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR) were determined. The films were a transparent, light greenish-yellow colour, with a uniform surface, and were flexible and easy to handle. The thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout the film. Mechanical properties were influenced by the film composition; films containing gelatin were more resistant to stress, while those containing ethylcellulose were more flexible. Increasing the adjuvant concentration decreased the elasticity and the rupture resistance, but increased the moisture uptake capacity and WVP of the formulations. BP was thermally stable as were the films. FTIR tests suggested interactions between BP and the adjuvants. This work could contribute to the utilization of BP to prepare films for food and pharmaceutical uses.

resumo Este estudo investigou o desenvolvimento e as características físico-químicas de filmes obtidos com o resíduo (BP), normalmente descartado, advindo da preparação de extratos de própolis. Os filmes foram produzidos com e sem adjuvantes poliméricos (gelatina ou etilcelulose) e propilenoglicol, pelo método de evaporação de solvente. Foram determinadas a densidade, a topografia de superfície usando microscopia eletrônica de varredura, as propriedades mecânicas (resistência à dobra, tensão e elongação), transmissão de vapor de água (WVP), capacidade de absorção de umidade, termogravimetria, calorimetria exploratória diferencial e espectroscopia de infravermelho com transformada de Fourier (FTIR). Os filmes demonstraram coloração verde-amarelada, transparência, uniformidade de superfície, homogeneidade, flexibilidade e fácil manuseio. A espessura e a densidade das preparações indicaram que os compostos estavam dispersos de forma homogênea. As propriedades mecânicas foram influenciadas pela composição dos filmes e aqueles que continham gelatina apresentaram-se mais resistentes enquanto os compostos por etilcelulose demonstraram maior flexibilidade. Com o aumento da concentração polimérica, a resistência e a elasticidade diminuíam, porém aumentou a capacidade de absorção de água e a WVP das formulações. BP apresentou estabilidade térmica assim como os filmes. Os testes de FTIR sugeriram interações entre o BP e os adjuvantes utilizados. Este trabalho pôde contribuir com a utilização de BP na preparação de filmes para uso alimentício e farmacêutico.

Propolis organogel as a novel topical delivery system for treating wounds.

CONTEXT: Propolis has traditionally been used in curing infections and healing wounds and burns. OBJECTIVE: The aim of this study is to formulate pluronic lecithin organogel of propolis to improve its availability and antimicrobial activity. MATERIALS AND METHODS: Different organogels were prepared by using soybean lecithin, isopropyl palmitate, pluronic F127 and water. The effect of quantity of lecithin and pluronic F127 and percentage of oil phase was investigated. The organogels were evaluated for appearance, texture, pH, drug content and viscosity. In vitro release studies were carried out using cellophane membrane. Drug permeation through abdominal rat skin from organogels that showed high % drug release was compared to that from propolis suspension in distilled water. Finally, the antimicrobial activity of the selected propolis formulation against different bacterial isolates was compared with that of propolis suspension in water. RESULTS AND DISCUSSION: Results showed that all organogel formulations except the formula containing 10% pluronic F127, showed acceptable physical properties. Drug content of organogel formulations was in the range of 97.5-100.2%. The pH of the formulations was in the range of 5.5-6.3 that suits the skin pH, indicating skin compatibility. The viscosity was in the range of 5366-8984 cp. A significant decrease in drug release from formulations was observed with increase in concentration of lecithin and pluronic F127. Decreasing oil phase percentage to 20% w/w led to a decrease in drug release from the formulation. CONCLUSION: The formula containing 3% lecithin and 20% pluronic F127 exhibited superior skin permeation and antimicrobial activity over propolis suspension in water.

Assessment of ion diffusion from a calcium hydroxide-propolis paste through dentin

This study evaluated the ability of ions from a non-alcoholic calcium hydroxide-propolis paste to diffuse through dentinal tubules. Thirty-six single-rooted bovine teeth were used. The tooth crowns were removed, and the root canals were instrumented and divided into 3 groups: Group 1 - calcium hydroxide-propylene glycol paste; Group 2 - calcium hydroxide-saline solution paste; Group 3 - calcium hydroxide-propolis paste. After the root canal dressings were applied, the teeth were sealed and placed in containers with deionized water. The pH of the water was measured after 3, 24, 72 and 168 hours to determine the diffusion of calcium hydroxide ions through the dentinal tubules. All of the pastes studied promoted the diffusion of calcium hydroxide ions through the dentinal tubules. Associating propolis to calcium hydroxide resulted in a pH increase, which occurred with greater intensity after 72 hours. The calcium hydroxide-propolis paste was able to diffuse in dentin.

Assessment of ion diffusion from a calcium hydroxide-propolis paste through dentin.

This study evaluated the ability of ions from a non-alcoholic calcium hydroxide-propolis paste to diffuse through dentinal tubules. Thirty-six single-rooted bovine teeth were used. The tooth crowns were removed, and the root canals were instrumented and divided into 3 groups: Group 1 - calcium hydroxide-propylene glycol paste; Group 2 - calcium hydroxide-saline solution paste; Group 3 - calcium hydroxide-propolis paste. After the root canal dressings were applied, the teeth were sealed and placed in containers with deionized water. The pH of the water was measured after 3, 24, 72 and 168 hours to determine the diffusion of calcium hydroxide ions through the dentinal tubules. All of the pastes studied promoted the diffusion of calcium hydroxide ions through the dentinal tubules. Associating propolis to calcium hydroxide resulted in a pH increase, which occurred with greater intensity after 72 hours. The calcium hydroxide-propolis paste was able to diffuse in dentin.

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

The correlation between the phenolic composition and biological activities of two varieties of Brazilian propolis (G6 and G12)

Biological assays that have been performed on different types of Brazilian propolis have shown that type 6 propolis (G6) has a strong antimicrobial activity and a low flavonoid content. This study aimed to evaluate the correlation between the phenolic composition and the biological activities displayed by propolis G6 from the state of Bahia and green propolis, also known as type 12 (G12). The values of the flavonoids and the total phenolics in propolis G6 were different than those in propolis G12. Although the G12 variety presented greater antioxidant activity, propolis G6 proved to have greater antimicrobial and cytotoxic activities. The results showed that the phenolic compounds may not be the only compounds responsible for the biological activity. More detailed studies of the chemical composition and an assessment of the biological activity are required to establish the quality of propolis.

Ensaios biológicos realizados com diferentes tipos de própolis brasileira têm mostrado que a própolis do tipo 6 (G6) tem forte atividade antimicrobiana e menor teor de flavonóides. Este trabalho teve como objetivo avaliar a correlação entre a composição fenólica e atividades biológicas apresentadas pela própolis G6, do Estado da Bahia, e a própolis verde, do tipo 12 (G12). Os teores de flavonóides e fenólicos totais na própolis G6 foram diferentes dos teores da própolis G12. Apesar da G12 apresentar maior atividade antioxidante, a própolis G6 apresenta maior atividade antimicrobiana e citotóxica. Os resultados mostraram que os compostos fenólicos não são os únicos compostos responsáveis pela atividade biológica da própolis. Estudos mais específicos da composição química, em adição à avaliação das atividades biológicas, são requeridos para determinar a qualidade da própolis.

Antibacterial activity of propolis-based toothpastes for endodontic treatment / Atividade antibacteriana de pastas dentífricas com base de própolis para tratamento endodôntico

This study evaluated the antibacterial activity of propolis-based toothpastes used as intracanal medication in endodontic treatment. The propolis-based toothpastes were prepared using an extract established in previous studies (identified as A70D and D70D). Calcium hydroxide paste was used as a control. The bacteria employed were Streptococcus mutans (ATCC 25175), Staphylococcus aureus (ATCC 6538), Staphylococcus aureus (ATCC 25923), Kocuria rhizophila (ATCC 9341), Escherichia coli (ATCC 10538), Pseudomonas aeruginosa (ATCC 27853), Enterococcus hirae (ATCC 10541), Streptococcus mutans (ATCC 25175). Five field strains isolated from saliva were used: Staphylococcus spp. (23.1 - coagulase positive), Staphylococcus spp. (23.5 - coagulase negative), Staphylococcus spp. (26.1 - coagulase positive), Staphylococcus spp. (26.5 - coagulase negative) and Staphylococcus epidermidis (6epi). The diffusion-well method on double-layer agar was used in a culture medium of Tryptic Soy Agar. The plates were kept at room temperature for two hours to allow the diffusion of pastes in the culture medium, and then incubated at 35º C for twenty-four hours in aerobiosis and in microaerophilia (S. mutans). After this period, the total diameter of the inhibition halo was measured. The results were analyzed by ANOVA analysis of variance, followed by the Tukey test at p<0.05. The propolis-based toothpastes presented antibacterial activity against 83.3 percent of the analyzed bacteria. For 66.7 percent of these bacteria, the propolis-based toothpastes exhibited greater antibacterial activity than calcium hydroxide. The present results allow us to conclude that the experimental pastes A70D and D70D showed good activity against aerobic bacteria, proving more effective than calcium hydroxide.

O objetivo deste estudo foi avaliar a atividade antibacteriana de formas farmacêuticas a base de própolis para uso no tratamento endodôntico como medicação intracanal. As formulações de própolis, em forma de pastas, foram preparadas a partir de um extrato pré-estabelecido em estudos anteriores e identificadas como A70D e D70D. Como controle, foi utilizado pasta de hidróxido de cálcio. As bactérias utilizadas foram: Streptococcus mutans (ATCC 25175), Staphylococcus aureus (ATCC 6538), Staphylococcus aureus (ATCC 25923), Kocuria rhizophila (ATCC 9341), Escherichia coli (ATCC 10538), Pseudomonas aeruginosa (ATCC 27853), Enterococcus hirae (ATCC 10541), Streptococcus mutans (ATCC 25175) e 5 cepas de campo isoladas da saliva: Staphylococcus spp. (23.1 - coagulase positiva), Staphylococcus spp. (23.5 - coagulase negativa), Staphylococcus spp. (26.1 - coagulase positiva), Staphylococcus spp. (26.5 - coagulase negativa) e Staphylococcus epidermidis (6epi). Foi utilizado o método poço difusão em camada dupla de ágar, em meio de cultura Tryptic Soy Agar. As placas foram mantidas à temperatura ambiente por 2 h para permitir a difusão das pastas no meio de cultura, e então incubadas a 35 ºC por 24 h em aerobiose e em microaerofilia (S. mutans). Após este período, foi medido o diâmetro total do halo de inibição. Os resultados foram submetidos ao teste de análise de variância ANOVA seguido do teste de Tukey com p<0,05. As pastas a base de própolis apresentaram atividade antibacteriana contra 83,3 por cento das bactérias analisadas. Para 66,7 por cento das bactérias, as pastas de própolis apresentaram maior atividade antibacteriana que o hidróxido de cálcio, e este foi mais efetivo apenas para Streptococcus mutans (ATCC 25175), Staphylococcus aureus (ATCC 25923) e Pseudomonas aeruginosa (ATCC 27853). De acordo com a metodologia utilizada, pode-se concluir que as pastas experimentais A70D e D70D apresentam boa atividade contra bactérias aeróbias...

Development of topical functionalized formulations added with propolis extract: stability, cutaneous absorption and in vivo studies.

Propolis, which is a natural product widely consumed in the folk medicine, is a serious candidate to be applied topically due to its outstanding antioxidant properties. So, the purpose of this study was to develop stable topical formulations added with propolis extract in an attempt to prevent and/or treat the diseases occurring in skin caused by UV radiation. The antioxidant activity using a chemiluminescent method was used to evaluate the functional stability and the permeation/retention in skin of these formulations. In the long-term stability study, the formulations were stored at 25+/-2 degrees C/AH and at 40+/-2 degrees C/70% RH for 360 days. It was found in this study, that the formulations prepared with Polawax showed functional and physical stability in the period of study. In addition, this formulation presented good results in the percutaneous study, allowing the antioxidant compounds present in the propolis extract to reach lower layers in pig ear skin and in the whole hairless mice skin (retention=0.12 and 0.13 microL of propolis/g of skin, respectively). In the in vivo study, it was also suggested that this formulation may be effective in protecting skin from UVB photodamage, nevertheless other assays need to be done in order to have a complete understanding of the protective effect of formulations added with propolis extract.

Atividade microbiana de óleos essenciais e extratos de própolis sobre bactérias cariogênicas / Antimicrobial activity of essential oils and propolis against oral pathogens

A própolis é uma resina produzida por abelhas a partir de diferentes plantas. Os óleos essenciais são produtosdo metabolismo secundário das plantas e usados durante anos na medicina popular como antimicrobianos. Oobjetivo deste trabalho foi avaliar o perfil de susceptibilidade dos extratos etanólicos de própolis oriundos dos Estados do Paraná, Minas Gerais e São Paulo e de óleos essenciais frente às bactérias cariogênicas Streptococcus mutans e Lactobacillus casei usando o método de difusão em ágar. Os resultados obtidos indicam a própolis do estado de Minas Gerais como a mais ativa de todas, o que leva a crer que a diferença observada na quantidade de própolis produzida e a diversidade dos metabólitos secundários, no produto, podem estar associados com a região de produção e com a estação climática da coleta. Os óleos essenciais mostraram atividades significantes para os microrganismos testados, alguns deles apresentando zona de inibição maior que o do controle positivo.

Propolis is a natural composite balsam, produced by honey bees (Apis melifera) from the gum of various plants. Essential oils and their components are products of the secondary metabolism of plants, used for many ears in folk medicine, principally, as antimicrobial. The aim of the present work was to analyze the differences in the antimicrobial activity of propolis obtained from three different regions of Brazil (Minas Gerais, Parana and São Paulo States) and of essential oils, using agar diffusion methods to test them against cariogenic microorganisms Streptococcus mutans and Lactobacillus casei. The results showed that the propolis from Minas Gerais State was more active than that from the others, and implied that the existing differences in the amount of propolis produced and diversity of secondary metabolites in the product may be associated with the region of production and the climatic season of collection. The essential oils displayed significant inhibitory activity against the microorganisms tested, showing larger inhibition zones than the positive control.

Effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in mice.

We studied the effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in ICR mice. Propolis granular A.P.C dose-related inhibited scratching behavior induced by compound 48/80 and significant inhibition were observed at 1000 mg/kg. However, histamine-induced scratching behavior was not inhibited by propolis granular A.P.C even at 1000 mg/kg. Propolis ethanol extract at 10 microg/ml or more inhibited histamine release from rat mast cells induced by compound 48/80. In addition, it blocked increased vascular permeability induced by compound 48/80. The inhibitory effect of propolis on scratching behavior induced by compound 48/80 was gradually enhanced by repeated administration, and 500 mg/kg propolis granular A.P.C, which caused no effect through single administration, significantly inhibited scratching behavior after repeated administration for 4 weeks. From these findings, it is assumed that the inhibition of scratching behavior induced by propolis occurs through a mast cell-dependent mechanism.