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.

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.

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.

Ensayo clínico aleatorizado sobre la efectividad de tratamientos alternativos en la estomatitis aftosa recurrente / Randomized clinical trial of the effectiveness of complementary therapies for recurrent aphthous stomatitis

Fundamento y objetivo: A pesar de la elevada prevalencia de la estomatitis aftosa recurrente (EAR), su etiología no está del todo aclarada y no existe un tratamiento totalmente curativo. El objetivo de este trabajo fue evaluar la eficacia clínica y la seguridad de 4 tratamientos (nitrato de plata, própolis, ruibarbo y nogal) de la EAR. Pacientes y método: Se realizó un ensayo clínico aleatorizado con 125 pacientes con aftas menores, con 25 pacientes por grupo: cauterización con nitrato de plata, própolis, extracto de ruibarbo, extracto de corteza de nogal y placebo. Resultados y conclusiones: Ningún paciente refirió efectos adversos relacionados con el tratamiento. Hay diferencias significativas (p<0,001) globales en el tiempo hasta la desaparición de los síntomas. El más rápido fue el nitrato de plata (1,16 días), después los 3 tratamientos alternativos (1,60 días con própolis, 1,84 con ruibarbo y 2,00 con nogal, sin diferencias entre ellos), y por último el placebo (4,64 días). En cuanto al tiempo medio de curación de las lesiones, fue estadísticamente mayor (8,96 días) para el placebo que para los 4 tratamientos: nitrato de plata (7,32 días), própolis (6,80), ruibarbo (7,72) y nogal (8,00) (AU)

Background and objective: Despite the high prevalence of recurrent aphthous stomatitis (RAS), its etiology is not yet completely clear and there is no completely remedial treatment available at present. The objective of this study was to evaluate the clinical efficacy and safety of 4 treatments (silver nitrate, propolis, rhubarb and walnut) for RAS. Patients and method: A randomized clinical trial was conducted with 125 patients with minor aphthae, including 25 patients per group: cauterization with silver nitrate, propolis, rhubarb extract, walnut extract and placebo. Results and conclusions: No patient reported adverse effects related to the treatment received. There were significant (P<.001) differences in the time elapsed until symptom resolution. The fastest treatment was silver nitrate (1.16 days), followed by the 3 alternative treatments (1.60 days with propolis, 1.84 with rhubarb and 2.00 with walnut; with no differences between them), and finally the placebo (4.64 days). The mean healing time of the lesions was statistically higher (8.96 days) for the placebo than for the 4 treatments: silver nitrate (7.32 days), propolis (6.80), rhubarb (7.72) and walnut (8.00) (AU)

Estudio de la actividad antioxidante y antitumoral del propóleo / Study on the antioxidant and antitumoral activity of propolis

Introducción: El propóleo es la sustancia que protege a la colmena, es una resina de composición compleja y viscosa que las abejas utilizan en la reparación y protección de la colmena. El material del que procede el propóleo son las resinas, brotes y pecíolos de las hojas de diferentes vegetales, por ello presenta una composición química muy compleja que varía en función de la flora de recolección de las abejas. Posee capacidad antimicrobiana, antiinflamatoria que está relacionada con su poder antioxidante, inmunomoduladora, entre otras. Objetivos: En este trabajo se estudian las actividades antioxidantes y antitumorales de propóleos de distintas zonas de la provincia de Málaga comparándolos con uno de la región de Bohemia al sur de la República Checa. Material y métodos: La actividad antioxidante se evaluó según el método ABTS+/S2O8K2. Además, se estimó la cantidad de proteínas totales a partir del contenido de nitrógeno y posteriormente se determinó la citotoxicidad y actividad antitumoral del propóleo del Puerto de la Torre, al norte de Málaga, según el método del bromuro de 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazolio. Resultados: Se observó que el propóleo presenta una elevada actividad antioxidante, aunque tiene una menor cantidad de proteínas. El propóleo presenta elevada toxicidad y mayor actividad antitumoral frente al cáncer de colon que al de leucemia. Conclusión: Con todos estos datos obtenidos se puede concluir que el propóleo presenta diferentes actividades de interés para la industria alimentaria o cosmética, entre las que destaca su elevado poder antioxidante y su capacidad como antitumoral

Introduction: Propolis is the substance that protects the hive, a resin of complex and viscous composition bees use in the repair and protection of the hive. The material from which propolis arises are the resins, shoots and petioles of the leaves of different plants, so it has a very complex chemical composition that varies depending on the flora of the bees collection. It offers an antimicrobial, anti-inflammatory capacity related to its antioxidant, immunomodulatory power, among others. Aims: In this work, antioxidant and antitumoral activities of different propolis collected from different areas of the province of Malaga, comparing them with one from the Bohemian region to the south of the Czech Republic are studied. Material and methods: Antioxidant activity was determined according to the ABTS+/S2O8K2 method. In addition, the quantity of total proteins from the nitrogen content and subsequently the cytotoxicity and antitumoral activity of the propolis of Puerto de la Torre, north of Malaga, are measured according to the 3-(4,5-dimetiltiazol-2-il)-2,5-diphenyl tetrazolium bromide method. Results: It was observed that propolis has high antioxidant activity, although it has a lower amount of proteins. Propolis has high toxicity and higher antitumoral activity against colon cancer than leukemia. Discussion: With all these data, it can be concluded that propolis offers different activities of interest, for the food and cosmetic industry, among which the high antioxidant and antitumoral capacity

Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice / Efectos renoprotectores del propóleo sobre la toxicidad renal aguda inducida por gentamicina en ratones albinos suizos

Antecedentes: El riñón es un órgano vital que desempeña una función importante e insustituible en la desintoxicación y la eliminación de los xenobióticos y, por lo tanto, es vulnerable a desarrollar diversas formas de lesión. Esto hace muy importante la búsqueda de compuestos renoprotectores naturales. Objetivos: Este estudio tiene como objetivo evaluar las propiedades renoprotectoras del propóleo contra la toxicidad renal inducida por gentamicina en ratones. Métodos: Para este estudio se utilizaron 3 grupos de 10 ratones macho en cada uno. El primer grupo sirvió como control, el segundo grupo (grupo Gm) recibió 80mg/kg de peso corporal de gentamicina por vía oral durante 7 días y el tercer grupo (grupo GmP) recibió la misma dosis de gentamicina con propóleo (500mg/kg de peso corporal) durante 7 días. Se utilizaron varios parámetros para estudiar la toxicidad renal. Resultados: La gentamicina causó daño renal significativo, como demostró el aumento de los niveles de nitrógeno ureico en sangre, la disminución de la hipocelularidad glomerular, los túbulos moderadamente dilatados y la pérdida leve del borde en cepillo, la infiltración grave, la degeneración tubular extensa y la presencia de cilindros tubulares. Los resultados de la histoquímica muestran presencia de colágeno y fibras reticulares. Las reacciones inmunohistoquímicas muestran lesión renal (expresión del gen Kim-1), estrés oxidativo (expresión del gen MDA) y un aumento de la apoptosis (expresión del gen caspasa-3). La administración concomitante de propóleo con gentamicina mostró disminución significativa de los niveles de nitrógeno ureico en la sangre, aspecto de glomérulos sanos con celularidad normal, reducción de la lesión tubular, disminución de colágeno y deposición de fibras reticulares, reducción de la apoptosis, daño renal y estrés oxidativo. Conclusión: Los resultados presentados en este estudio muestran claramente la función renoprotectora del propóleo contra la toxicidad inducida por gentamicina en el riñón de los ratones (AU)

Background: Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. Objectives: This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Methods: Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Results: Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Conclusion: Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney (AU)

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.

Protective role of propolis on diazinon induced nephrotoxicity in adult male albino rats

Diazinon has been reported to produce oxidative stress and adverse effects on many organs. In contrast, propolis components behave as hydrophilic antioxidants. To evaluate the protective effect of propolis on diazinon-induced nephrotoxicity in adult male albino rats, eighty adult male albino rats were divided randomly into four groups: control, diazinon treated, propolis treated and diazinon plus propolis groups. Control group were divided into two subgroups: the first was not given any treatment and the second one received 1.5 ml of sterile distilled water through intra-gastric tube daily for 4 consecutive weeks. The diazinon group was treated with 10 mg/kg through intra-gastric tube, daily for 4 weeks. The propolis group received 50 mg/kg through intra-gastric tube, daily for 4 weeks. The diazinon-plus-propolis group was treated with the same doses as previous groups. Kidneys were removed and processed for haematoxylin and eosin, caspase-3 immunostaining and electron microscopic examination. Renal tissues of diazinon-treated rats showed histopathological and ultrastructural changes such as shrunken glomerulus, hemorrhage, congestion, increased Bowman’s space, inflammatory infiltration, degenerated tubules with vacuolated epithelial cell lining, pyknosis and necrotic debris. Rats of the diazinon-plus-propolis group showed a marked reduction in these pathological features. We conclude that propolis can ameliorate the nephrotoxicity induced by diazinon

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Propolis protects against high glucose-induced vascular endothelial dysfunction in isolated rat aorta

While propolis is known to have abundant bioactive constituents and a variety of biological activities, it is not clear whether propolis has beneficial effects on high glucose-mediated vascular endothelial impairment. The aim of the present study was to investigate the potential protective effect of propolis extract against the acute vascular endothelial dysfunction resulting from exposure to high glucose load and to elucidate its underlying mechanism. Rat aortic rings were incubated with normal glucose (11 mM), high glucose (44 mM), or mannitol (44 mM) for 3 h with or without propolis extract (400 ìg/ml). Contraction to phenylephrine (Phe, 10−9–10−5 M) and relaxation to acetylcholine (ACh, 10−9–10−5 M) and sodium nitroprusside (SNP, 10−9–10−5 M) were measured before and after incubation. Changes in malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were also measured. Phe-induced contraction was impaired by high glucose as the E max decreased from 138.87 ± 11.43 to 103.65 ± 11.5 %. In addition, ACh-induced relaxation was impaired as the E max decreased from 99.80 ± 7.25 to 39.20 ± 6.5 %. SNP-induced relaxation was not affected. Furthermore, high glucose decreased the levels of both SOD (by 6 U/ml) and GSH (by 68 %) and increased levels of MDA (by 85 %). Propolis extract prevented high glucose-induced impairment of Phe and ACh responses and increased both SOD and GSH, leading to decreased MDA levels. In conclusion, propolis can protect against high glucose-induced vascular dysfunction by reducing oxidative stress (AU)

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.

Positive influence of a natural product as propolis on antioxidant status and lipid peroxidation in senescent rats

Given the importance of oxidative stress associated to aging, it would be interesting to assess the effect of oral supplementation with antioxidant substances capable of diminishing oxidative aggression and free radicals generation associated to this condition. This study investigated the effects of AIN-93 M diet supplemented either with 2 % of propolis, or with 4 % of a natural product obtained from lyophilizate vegetables, selected by its antioxidant properties, in senescent healthy Wistar rats fed ad libitum over 3 months. Propolis supplementation leads to a lower level of glucose and cholesterol concentrations together with a reduction in protein oxidation. Plasma thiobarbituric acid-reactive substance levels were lower in the rats consuming the natural vegetable product and propolis possibly due to its antioxidant components, neutralizing the free radical produced, and thus preventing cellular damage. The results of the present study suggest a synergic effect of overall propolis compounds reducing the oxidative stress and glucose and cholesterol plasma levels associated with aging (AU)

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.