Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Immunomodulatory Effect of Propolis on Foxp3 Gene Expression in Human Peripheral Blood Mononuclear Cells Stimulated in vitro with Pseudomonas Aeruginosa Ag.

Immune balance during infection is critical for both supporting the defense of the immune system of the body and preventing an overly aggressive immune response. Foxp3, a transcription factor of regulatory T cells, plays a critical role in balancing the immune system of the body. Propolis has been shown to affect Foxp3 expression. This study aimed to verify the effect of propolis extracts on in vitro Foxp3 gene expression in peripheral blood mononuclear cells (PBMCs) stimulated with Pseudomonas aeruginosa Ag. In this study, a total of 20 apparently healthy volunteers were included, with 10 males and 10 females within the age range of 20-40 years old. Five ml of blood were drawn from each participant to assess Foxp3 gene expression in PBMCs using density gradient lymphoprep and stimulated with P.aeruginosa lipopolysaccharide (LPS) in vitro. The samples were divided into four distinct groups as follows: LPS stimulated PBMCs, ethanol-extracted propolis (EEP) + LPS stimulated PBMCs, and water-extracted propolis (WEP) + LPS stimulated PBMCs and PBMCs as the control group. The Foxp3 gene expression level was estimated in all four groups following a period of 48 h of cultivation by real-time polymerase chain reaction technique using SYBR green dye. Results of the study indicated that propolis had a great effect on the mRNA Foxp3 expression. Both EEP and WEP had immunomodulatory effects through the Foxp3 mRNA expression, both the EEP and WEP could significantly inhibit Foxp3 mRNA gene expression by human PBMCs after stimulation with pseudomonas Ag in vitro. Propolis exhibited an immunoregulatory effect which was the same with ethanol and water extracts on Foxp3 mRNA gene expression.

Chemical composition and antimicrobial activity of two extract of propolis against isolates of Staphylococcus spp. and multiresistant bacterials / Composição química e atividade antimicrobiana de dois extratos de própolis contra isolados de Staphylococcus spp. e bactérias multirresistentes

There is a growing need to discover and develop alternative therapies for the treatment of mastitis caused by Staphylococcus spp. and multidrug-resistant bacterial infections. This study examined the chemical composition and antimicrobial potential of two propolis extracts (EPA and EPB) against seventy-seven isolates of Staphylococcus spp. obtained from subclinical bovine mastitis; three clinical strains of MRSA and two from clinical strains of S. aureus ATCC, identified as S. aureus ATCC 6538 and S. aureus ATCC 25923. The total phenolic content was determined by the Folin-Ciocalteau method, the total flavonoid content by the Dowd method and the phenolic profile was quantified by HPLC-DAD. The MBC values of the extracts were evaluated by broth microdilution method. The amount of total phenolic and flavonoid compounds was higher in EPA than EPB. Both extracts revealed the presence of caffeic, coumaric, cinnamic, ferulic and 3,4-dihydroxybenzoic acids, with higher concentrations of coumaric and cinnamic acids. Staphylococcus spp. isolates were susceptible to EPA (90.9%), EPB (83.1%) and oxacillin (80.5%). The oxacillin susceptible isolates were also susceptible to EPA (70.1%) and EPB (80.6%), whereas those oxacillin-resistant strains were also susceptible to EPA (40.0%) and to EPB (26.7%). MBC ranged from 34.3 to 68.7µm/mL for EPA and from 68.7 to 137.5µg/mL for EPB. Both extracts inhibited significantly (100%) the clinical strains of MRSA, S. aureus ATCC 6538 and S. aureus ATCC 25923 at the concentration of 68.7µg/mL. It is concluded that both extracts of propolis, whose main constituents are coumaric and cinnamic acids, have high antimicrobial activity against the microorganisms studied, and EPA also against oxacillin-resistant strains. These findings reinforce its potential use for the treatment of bovine mastitis.(AU)

É cada vez mais oportuna a necessidade de descobrir e desenvolver terapias alternativas para tratamento da mastite causada por Staphylococcus spp. e de infecções bacterianas multirresistentes. Este estudo examinou a composição química e o potencial antimicrobiano de dois extratos etanólicos de própolis (EPA e EPB) contra setenta e sete isolados de Staphylococcus spp. obtidos a partir de mastite bovina subclínica; três estirpes clínicas de MRSA e duas de linhagens clínicas de S. aureus ATCC, identificadas como, S. aureus ATCC 6538 e S. aureus ATCC 25923, ambas metacilina resistentes. O teor total de fenólicos foi determinado pelo método de Folin-Ciocalteau, o teor de flavonoides totais pelo método Dowd e o perfil fenólico foi quantificado por HPLC-DAD. CBM dos extratos foi avaliada pelo método de microdiluição em caldo. A quantidade total de compostos fenólicos e flavonoides foi maior no EPA do que no EPB. Ambos os extratos revelaram a presença dos ácidos cafeico, cumárico, cinâmico, ferúlico e 3,4-di-hidroxibenzóico, com maiores concentrações de ácidos cumárico e cinâmico. Os isolados de Staphylococcus spp. foram sensíveis a EPA (90,9%), EPB (83,1%) e oxacilina (80,5%). Os isolados suscetíveis à oxacilina também foram suscetíveis ao EPA (70,1%) e ao EPB (80,6%), enquanto os do resistente à oxacilina foram suscetíveis ao EPA (40,0%) e ao EPB (26,7%). MBC variou de 34,3 a 68,7µm/mL para EPA e de 68,7 a 137,5µg/mL para EPB. Ambos os extratos inibiram significativamente (100%) as linhagens clínicas de MRSA, S. aureus ATCC 6538 e S. aureus ATCC 25923 na concentração de 68,7µg/mL. Conclui-se que os extratos etanólicos da própolis, cujos principais constituintes são os ácidos cumário e cinâmico, possuem atividade antimicrobiana contra os micro-organismos estudados, e o EPA também contra as cepas resistentes à oxacilina. Estes achados reforçam seu potencial uso para o tratamento da mastite bovina.(AU)

Hand eczema among Dutch beekeepers - a cross-sectional study.

BACKGROUND AND OBJECTIVES: Studies of beekeepers have mostly focused on contact allergy to propolis. The overall prevalence of hand eczema (HE) in beekeepers has not been studied. Our objectives were to gain insight into the prevalence of HE in the Dutch beekeeper population; to define the impact of beekeeping activities on HE and vice versa; and to determine associated factors. PATIENTS AND METHODS: We used a cross-sectional online survey. Dutch beekeepers answered questions on beekeeping activities, the prevalence and characteristics of HE, including severity, and the impact of the disease on beekeeping. RESULTS: We analyzed 833 surveys (12 % of Dutch beekeepers). The one-year prevalence of HE was 13.2 %, and the lifetime prevalence was 20.5 %. In 28 patch-tested beekeepers with hand eczema, eight (28.6 %) were allergic to propolis. Atopic dermatitis was the only variable associated with HE: the odds ratio was 4.53 (95 % confidence interval 2.78-7.38). One in three beekeepers reported that HE was caused or worsened by beekeeping, although only 3.8 % reported working less at beekeeping because of HE, and the impact of HE on beekeeping activities (as perceived by beekeepers) is low. CONCLUSIONS: In this sample of Dutch beekeepers, hand eczema was more prevalent than in the general population, but seems to have had little impact on the beekeeping activities of the majority of beekeepers.

Beneficial Effects of Poplar Buds on Hyperglycemia, Dyslipidemia, Oxidative Stress, and Inflammation in Streptozotocin-Induced Type-2 Diabetes.

The effects of propolis on blood glucose regulation and the alleviation of various complications caused by diabetes have been widely studied. The main source of propolis in the northern temperate zone is poplar buds. However, there is limited research on the antidiabetic activity of poplar buds. In order to evaluate the effect of poplar buds on type-2 diabetes, crude extract and 50% fraction of poplar buds were used to feed streptozotocin-induced type-2 diabetic mice. The results showed that 50% fraction could increase insulin sensitivity and reduce insulin resistance, as well as decrease the levels of fasting blood glucose, glycated hemoglobin, and glycosylated serum proteins in diabetic mice. Compared with the model control group, the 50% fraction-treated group showed significant decreases of malondialdehyde (MDA) and increases of superoxide dismutase (SOD) in serum and liver homogenate. Moreover, 50% fraction could significantly decrease total cholesterol (TC), alleviate abnormal lipid metabolism, and enhance antioxidant capacity in the serum. For inflammatory factors, feeding of 50% fraction could also reduce the levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) in liver homogenate. Taken together, our results suggest that crude extract and 50% fraction of poplar buds, particularly the latter, can decrease blood glucose levels and insulin resistance, and 50% fraction can significantly relieve dyslipidemia, oxidative stress, and inflammation caused by type-2 diabetes.

Inhibitory effects of flavonoids extracted from Nepalese propolis on the LPS signaling pathway.

Flavonoids, particularly those derived from plants, harbor biological effects such as anti-inflammation and the inhibition of cancer progression. In the present study, we investigated the effects of 10 kinds of flavonoids isolated from Nepalese propolis on the LPS signaling pathway in order to clarify their anti-inflammatory activities. Five types of flavonoids: isoliquiritigenin, chrysin, 3',4'-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, and cearoin, markedly inhibited inflammatory responses including LPS-induced NO production by suppressing the expression of iNOS mRNA and LPS-induced mRNA expression of TNFα and CCL2. Their inhibitory effects on LPS-induced inflammatory responses correlated with the intensities of these flavonoids to suppress the LPS-induced activation of nuclear factor κB (NF-κB), an essential transcription factor for the mRNA expression of iNOS, TNFα, and CCL2. Among these flavonoids, 3',4'-dihydroxy-4-methoxydalbergione and 4-methoxydalbergion markedly inhibited the LPS-induced activation of IKK, thereby abrogating the degradation of IκBα and nuclear localization of NF-κB. On the other hand, isoliquiritigenin, chrysin, and cearoin failed to inhibit these signaling steps, but suppressed the transcriptional activity of NF-κB, which caused their anti-inflammatory effects. The results of the present study revealed that these five kinds of flavonoids are the components of Nepalese propolis that exhibit anti-inflammatory activities with a different regulatory mechanism for the activation of NF-κB.

Skin diseases in musicians.

Instrumental musicians are a risk group for skin diseases. A systematic review was performed on Pubmed database and in the musical literature. Most publications on dermatoses in musicians are case reports. The exact prevalence of skin diseases in musicians is unknown but high rates have been reported. The most at-risk musicians are percussionists, string and wind instrumentalists. Repeated physical trauma is a frequent cause of skin conditions in musicians (callosities, fiddler's neck syndrome…). The allergens most often reported in musicians' allergic contact dermatitis are metals (nickel, dichromate), exotic woods and cane reed components, colophony and propolis. The key preventive measures are early management of the skin disease, specific tests and avoidance of the causative allergens, together with better adjustment of playing techniques to reduce trauma.

Anti-inflammatory activity of flavonoids in Nepalese propolis is attributed to inhibition of the IL-33 signaling pathway.

Propolis has been used in folk medicine to improve health and prevent inflammatory diseases; however, the components that exhibit its anti-inflammatory activity remain unknown. We herein investigated the effects of flavonoids isolated from Nepalese propolis on the IL-33 signaling pathway to clarify the anti-inflammatory mechanism involved. Of the 8 types of flavonoids isolated from Nepalese propolis, 4 types of compounds, such as 3',4'-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin, markedly inhibited the IL-33-induced mRNA expression of inflammatory genes including IL-6, TNFα and IL-13 in bone marrow-derived mast cells (BMMC). These four flavonoids also inhibited the IL-33-induced activation of nuclear factor κB (NF-κB), which was consistent with their inhibitory effects on cytokine expression. The effects of these flavonoids are attributed to inhibition of IL-33-induced activation of IKK, which leads to the degradation of IκBα and nuclear localization of NF-κB. On the other hand, other flavonoids isolated from Nepalese propolis, such as isoliquiritigenin, plathymenin, 7-hydroxyflavanone, and (+)-medicarpin, had no effect on the IL-33 signaling pathway or cytokine expression. Therefore, these results indicate that 3',4'-dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin are the substances responsible for the anti-inflammatory activity of Nepalese propolis.

Immunomodulatory properties of green propolis.

Propolis is a resinous material collected by honeybees from numerous plants and serves as a defense against intruders. Because of its relevant curative properties, it is now gaining popularity in health foods and in cosmetic products. Understanding the underlying molecular mechanisms of phytochemicals has become a good strategy in bioprospection for new anti-inflammatory compounds. The biological activity of propolis derives from its high levels of phenolic acids, while flavonoids are thought to account for the activity of propolis extracts. The comprehension of the relationship between propolis and the immune system has progressed in the last years, recent articles have provided important contributions to this investigation field. Studies have shown that propolis suppressed the "IL-6-induced phosphorylation of signal transducer and STAT3", an essential cytokine-activated transcription factor in Th17 development. Therefore, action mechanisms of "propolis on Th17 differentiation could be instrumental in controlling disturbed cytokine networks in inflammation, autoimmune diseases, and infections." The use of propolis has been proposed in some patents as: WO201363714; CN102885854, WO2013142936, US20130266521, and US20130129808, which are related to the treatment of dental diseases; adjuvant in anti-cancer treatment; in cosmetic products; as an anti-inflammatory agent and natural antibiotic. Although there are many publications regarding the propolis efficacy, its applicability to human health and mechanisms of action are not completely understood, creating opportunities for new studies.

Microemulsion can improve the immune-enhancing activity of propolis flavonoid on immunosuppression and immune response.

The objective of the present study was to investigate whether the immune-enhancing activity of propolis flavone (PF) could be improved after PF was made into PF microemulsion (PFM). Two experiments were carried out. In immunosuppression experiment, the immune-enhancing effect of PFM in immunosuppressive chickens was performed. The results showed that PFM at high and medium doses was able to overcome the CTX-induced immunosuppression, significantly increases the immune organ indexes, enhances lymphocyte proliferation and improves the concentrations of IL-2 and IL-6 in serum when compared with PF. In immune response experiment, the adjuvant effect of PFM at three doses and PF were compared on chickens which were immunized intramuscularly with Avian Influenza Recombinant Newcastle Disease Virus bivalent Vaccine. The results showed that PFM at high and medium doses could significantly promote lymphocyte proliferation, enhances antibody titer and the concentrations of IgG and IgM, and its efficacy were significantly better than PF at most time points. These results indicated that PFM could significantly improve the immune-enhancing activity and adjuvanticity of PF, and its high and medium doses possessed the best efficacy. Therefore, the microemulsion could be used as an effective formulation for enhancing the bioavailability of PF.

Allergic reactions to insect secretions.

Some products derived from insects can induce allergic reactions. The main characteristics of some products from honeybees, cochineal and silkworms are summarised here. We review allergic reactions from honey-derived products (propolis, wax, royal jelly), from cochineal products (shellac and carmine) and from silk : clinical features, allergological investigations and allergens if they are known.

Geoprópolis de Melipona fasciculata SMITH: ações citotóxica, imunomoduladora, antibacteriana e antifúngica / Geopropolis of Melipona fasciculata SMITH: cytotoxica actions, immunomodulatory, antibacterial and antifungal

Própolis é composta por substâncias resinosas, coletadas de várias plantas por abelhas africanizadas, adicionando pólen, cera e secreções glandulares, enquanto para a produção de geoprópolis (Geo) as abelhas sem ferrão utilizam materiais resinosos de plantas, cera, e ainda acrescentam terra ou barro. As atividades biológicas da própolis produzida por Apis mellifera têm sido extensivamente estudadas, mas ainda são escassos os trabalhos sobre as propriedades da geoprópolis. Assim, o presente trabalho se propôs a investigar as atividades citotóxica, imunomoduladora, antibacteriana e antifúngica do extrato hidroalcoólico de geoprópolis de Melipona fasciculata Smith. Foi realizada a caracterização química da Geo, verificando que o principal grupo de compostos encontrados foram triterpenos. No tocante às células do carcinoma da laringe humana (HEp-2), Geo apresentou ação inibitória em concentrações mais elevadas; entretanto, esta ação foi somente citostática. Geo apresentou ação imunomoduladora sobre monócitos humanos, estimulando a produção das citocinas estudadas (TNF-α e IL-10). Não foi observada ação antibacteriana contra S. aureus e E. coli, havendo inibição destas linhagens somente com altas concentrações do extrato. Contudo, a associação de Geo com antibióticos favoreceu a ação do cloranfenicol sobre S. aureus. A Geo exerceu ação inibitória sobre Pythium insidiosum, tanto para o isolado obtido de caso humano como de eqüinos. Os resultados sugerem que a Geo apresentou inúmeras propriedades biológicas; contudo, sua ação é menor em comparação à própolis produzida por abelhas africanizadas, talvez devido ao baixo rendimento do extrato e sua difícil solubilidade...

Propolis is composed of resinous substances collected from various plants by Africanized honeybees, adding polen, wax and bee secretions, while for geopropolis (Geo) production stingless bees use resinous materials from plants, wax, but also adding mud or clay. The biological activities of propolis produced by Apis mellifera have been extensively studied, but there are few studies on Geo properties. Thus, the present study investigated the cytotoxic, immunomodulatory, antibacterial and antifungal activities of hydroalcoholic extract of Geo produced by Melipona fasciculata Smith. The chemical characterization of Geo was performed, revealing that the main group of compounds was triterpenes. Geo exerted an inhibitory action on human larynx carcinoma cells (HEp-2) using high concentrations, however, it was only a cytostatic action. Geo exhibited immunomodulatory effects on human monocytes, stimulating cytokines production (TNF-α and IL-10). No antibacterial activity was seen against S. aureus and E. coli. However, the combination of Geo with chloramphenicol favored its effect against S. aureus. Geo exerted an inhibitory action against Pythium insidiosum, both for human or equine isolates. Data suggested that Geo presented several properties; however, its activity is lower compared to propolis produced by honeybees, perhaps due to the low yield of the extract and its difficult solubility...

The use of propolis as vaccine's adjuvant.

The success of many vaccines relies on their association with selected adjuvants in order to increase their immunogenicity and ensure long-term protection. All available adjuvants have adverse effects due to their toxicity and reactogenicity. Pre-clinical in vivo investigations can identify new natural products for further applications. Several studies have confirmed the different medicinal benefits of propolis. However the studies that addressed its use as a potent, safe, vaccine adjuvant were limited to specific countries and languages, primarily Chinese. Those studies introduced the use of different extracts and formulations of propolis as adjuvants for bacterial, viral, and parasitic vaccines. This comprehensive up-to-date review categorizes, documents, and discusses those trials in a clear chronological manner.

Propóleos, inmunología y enfermedad de Peyronie / Propolis, Immunology and Peyronie's disease

Introducción: En varias investigaciones anteriores publicadas, hemos demostrado mejoría clínica de la enfermedad de Peyronie (EP) con propóleos. De las propiedades del propóleos, la inmunoestabilizadora es la que, hipotéticamente, produce dichos efectos. Objetivos: Analizar y conocer la correlación de la EP, el propóleos, la inmunología y la mejoría clínica. Material y métodos: Estudio prospectivo, pareado, ensayo clínico. Se estudian 30 pacientes. Dosis de 900 mg de propóleos diario durante 6 meses. Variables estudiadas: edad, raza, dirección de la curvatura, dolor, tamaño de la placa (pre y postratamiento) medida por exploración física, ecografía y ángulo de curvatura, dosificaciones de IgA, IgG, IGm, C3, C4, factor reumatoideo, proteína C reactiva, pruebas cutáneas. Resultados: La edad no presentó un predominio significativo. En cambio respecto a la raza, el 70% eran blancos. La curvatura, predominantemente, fue hacia arriba (40%). Con dolor consultó el 53,3%, siendo más manifiesto en los que tenían una curvatura hacia arriba (8 de los 12 casos). La modificación promedio en el grado de angulación (pre vs. postratamiento) fue de 38,1 g (pretratamiento) vs. 29,5 g (postratamiento) (p < 0,001). La variación en el tamaño de la placa, expresada en medición promedio de cada una de las 3 dimensiones, fue: medición física (cm) (1,9 × 1,3 × 1,3 pretratamiento) vs. (1,5 × 1,1 × 1,1 postratamiento) (p < 0,008, p < 0,0003, p < 0,0003); medición ecográfica (mm) (12,6 × 7,8 × 11,4 pretratamiento) vs. (11,7 × 7,5 × 5,1 postratamiento), p < 0,005). Pruebas humorales inmunológicas: C3 bajo en la mayoría de los pacientes. C4 rango normal. Aumento de C3 postratamiento a niveles normales y en las restantes que tenían niveles normales, pero en rangos limítrofes normales inferiores, aumentaron postratamiento (IGg, IGm, IGa y C4): en la inmunidad celular pretratamiento, pacientes inmunodeprimidos 18, moderadamente deprimidos 2 y normales 10 (33,3%). Postratamiento, sólo 1 paciente inmunodeprimido. Discusión: Al evaluar las variables principales de la investigación, observamos que la angulación del pene después del tratamiento durante 6 meses con propóleos se redujo notablemente, así como el tamaño de la placa medida físicamente por el investigador, y ecográficamente por el imagenólogo, se redujo al finalizar el tratamiento. Y, finalmente, analizando el sistema inmunológico de los pacientes tratados antes y después del tratamiento, los que lo tenían deprimido en mayor o menor grado se normalizaron, y otros pacientes cuyas cifras en los test eran normales, pero en el límite inferior de los valores referenciales, aumentaron al finalizar el tratamiento. Conclusiones: Existe una relación de inmunología deprimida en pacientes afectos de EP. La mejoría clínica de estos pacientes con EP, tratados con propóleos, se asocia a la mejoría inmunológica. Con un tratamiento de propóleos, se reduce el ángulo de curvatura del pene, la placa disminuye su tamaño y mejora su estado inmunológico deficiente (AU)

Introduction: In several previously published articles, we have shown clinical improvement in Peyronie's disease (PD) with propolis. Among the properties of propolis, immunostabilization is that which hypothetically corresponds to these effects. Objectives: To analyze and determine the associations among PD, propolis, immunology and clinical improvement. Material and methods: We performed a prospective, paired clinical trial of 30 patients. A dose of 900 mg propolis daily was administered for 6 months. The variables studied were age, race, direction of the curvature, pain, size of the plaque (pre- and post-treatment), as measured by physical examination, ultrasound and angle of curvature; levels of IgA, IgG, IGm, C3, C4, rheumatoid factor and C-reactive protein, and the results of skin tests. Results: There was no predominant age, while 70% of the patients were white. The curvature was predominantly upwards (40%).Pain was present in 53.3%, and was more frequent when the curvature was upwards (8 of the 12 patients). The mean change in the degree of angulation (pre- vs. post- treatment) was 38.1º(pre-treatment) vs. 29.5º(post-treatment) (p < 0.001). The variation in the size of the plaque, expressed as the mean of each of the three dimensions was as follows: physical measurement (cm) (1.9×1.3×1.3 pre-treatment) vs. (1.5×1.1×1.1 post-treatment) (p<0.008, p<0.0003, p<0.0003); ultrasound measurement (mm) (12.6x7.8×11.4(pre-treatment) vs. (11.7×7.5×5.1 post-treatment) (p < 0.005). The results of humoral immunological tests were as follows: C3 levels were low in the majority of the patients; C4 levels were within the normal range; C3 concentrations increased after treatment to within the normal range and levels increased after treatment in the remaining patients who had levels at the lower limit of normal before treatment. The results of cellular immunity tests (IGg, IGm, IGa and C4) showed that before treatment 18 patients were immunodepressed, two showed moderate immunodepression and 10 showed normal cellular immune function (33.3%). After treatment, only one patient was immunodepressed. Discussion: On evaluating the main variables, we found that the angle of the penis after 6 months of treatment with propolis was significantly reduced. The size of the plaque measured physically by the physician and sonographically by the sonographer was also reduced at the end of the treatment. In patients who were immunodepressed before treatment, immune function returned to normal to a greater or lesser extent. Patients with low values before treatment showed improved immune function after treatment. Conclusions: There is an association between immunodepression and PD. The clinical improvement in patients with PD treated with propolis was associated with improved immune function. Propolis reduces the angle of penile curvature and the size of the plaque and improves immune function (AU)

The effects of propolis and its isolated compounds on cytokine production by murine macrophages.

Since propolis and phenolic compounds, such as cinnamic and coumaric acids, have several biological properties, their immunomodulatory effect on cytokine production (IL-1ß, IL-6 and IL-10) was investigated. Peritoneal macrophages from BALB/c mice were incubated with propolis, coumaric and cinnamic acids in different concentrations and the concentrations that inhibited cytokine production were tested before or after macrophage challenge with LPS, to evaluate a possible immunomodulatory action. Propolis and the acids stimulated IL-1ß production, while IL-6 production was significantly inhibited after incubation with propolis (5, 50 and 100 µg/well), coumaric and cinnamic acids (50 and 100 µg/well). In LPS-challenge protocols, inhibitory concentrations of cinnamic and coumaric acids after LPS incubation prevented efficiently its effects on IL-6 production, whereas propolis inhibited LPS effects both before and after its addition. Propolis, coumaric and cinnamic acids (50 and 100 µg/well) inhibited IL-10 production as well. Both acids showed a similar inhibitory activity on IL-10 production when added after LPS challenge, while propolis counteracted LPS action when added before and after LPS incubation. Propolis modulated the immune/inflammatory response, depending on the concentration. Its efficiency may occur due to the synergistic effect of its compounds, and cinnamic and coumaric acids may be involved in the action of propolis on cytokine production.

Indicadores físico-químicos e atividade antibacteriana de própolis marrom frente à Escherichia coli / Physico-chemical indicators and antibacterial activity of brown propolis against Escherichia coli

The activity of 23 samples of ethanolic brown propolis, from the State of Mato Grosso, was investigated against Escherichia coli ATCC 25922. The values of physical and chemical parameters showed significant variation among samples. The percentage of dry extract ranged from 2.6 to 27.6 percent. The index of oxidation varied from 3 to 519 seconds. All samples showed the percentage of wax higher than the limit preconized by the legislation, with values varying from 3.4 to 74.6 percent. The quantification of phenolic and flavonoid compounds, responsible for antimicrobial activity, ranged from 0.1 to 5.0 (w/w) and 0.02 to 0.66 (w/w), respectively, being that the higher the index of phenolic compounds the larger the zones of inhibition. Antibacterial activity was observed in seven out of the 23 samples, demonstrating zones of inhibition ranging from 10 to 11.3mm. For these active samples, the minimum inhibitory concentration was determined, ranging from 125 to 1000mg/mL. The value of MIC in 42.9 percent of these samples was 250mg/mL. These results contribute to the establishment of physical and chemical parameters for the regulation of brown propolis and indicate possible therapeutic applicability in the development of formulations for the treatment of infections caused by E. coli.

Protective effect of propolis against oxidative stress and immunosuppression induced by oxytetracycline in rainbow trout (Oncorhynchus mykiss, W.).

The aim of this study was to investigate the effects of propolis on oxytetracycline (OTC)-induced oxidative stress and immunosuppression in fish. OTC (100 mg per kg⁻¹ body weight) was orally administered to fish for 14 days. A significant elevation in the level of malondialdehyde, as an index of lipid peroxidation, and reductions in antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) and low molecular weight antioxidant (reduced glutathione) levels were observed in the blood, liver, kidney, spleen, and heart tissues of OTC-treated fish. OTC also had a suppressive effect on specific and non-specific immune system parameters, such as leucocyte counts, oxidative radical production (nitrobluetetrazolium activity), total plasma protein and immunoglobulin levels, and phagocytic activity. Pre-treatment, post-treatment, and simultaneous treatment with propolis (50 mg per kg⁻¹ body weight, orally) attenuated the OTC-induced oxidative stress by significantly decreasing the levels of malondialdehyde in tissues. In addition, propolis significantly increased the level of reduced glutathione and the catalase, glutathione peroxidase, and superoxide dismutase activities. Upon the administration of propolis, the suppressed immune system parameters were significantly increased in fish treated with OTC. The present results suggest that pre-treatment, post-treatment, and simultaneous administration of propolis might alleviate OTC-induced oxidative stress and immunosuppression.

The immune enhancement of propolis adjuvant on inactivated porcine parvovirus vaccine in guinea pig.

Two experiments were carried out. In immune response test, the immune enhancement of propolis, oilemulsion and aluminium salt were compared in guinea pig vaccinated with inactivated porcine parvovirus (PPV) vaccine. The result showed that three adjuvants could enhance antibody titer, T lymphocyte proliferation, IL-2 and IL-4 secretion of splenic lymphocyte. The action of propolis was similar to that of oilemulsion and superior to that of aluminium salt, especially in early period of vaccination propolis could accelerate antibody production. In immune protection test, the effects of three adjuvants on PPV infection were compared in guinea pig vaccinated with PPV vaccine then challenged with PPV. The result showed that propolis and oilemulsion could enhance the antibody titer, IL-2 and IL-4 content in serum and decrease the PPV content in blood and viscera. In the effect of improving cellular immune response, the propolis was the best. These results indicated that propolis possessed better immune enhancement and would be exploited into a effective adjuvant of inactivated vaccine.