Effects Of Brazilian Green Propolis Research Articles

Effect of Brazilian green propolis in chronic ulcer treatment: a randomized clinical trial

RESUMO Objetivo: avaliar a eficácia da própolis verde brasileira a 5% (pomada) em indivíduos com úlceras crônicas. Métodos: ensaio clínico randomizado, desenvolvido com 40 pacientes aleatorizados igualmente para grupo controle (tratado com ácido graxo essencial) e grupo experimental (tratado com própolis verde a 5%) por 30 dias. Os desfechos de interesse foram características sociodemográficas, clínicas e laboratoriais, características das lesões, como tipo de tecido no leito, presença de exsudato, características da borda, conteúdo microbiano e dor. Resultados: quanto às características sociodemográficas, clínicas e laboratoriais, os dois grupos não apresentaram diferença estatisticamente significativas. Após avaliação em 30 dias, observou-se efeito para os dois grupos tratados, porém, para o grupo experimental, maior eficácia quanto ao tipo de tecido no leito, tipo de exsudato, característica da borda, conteúdo microbiano e dor. Conclusão: a pomada a base de própolis mostrou efeito cicatrizante, apresentando-se como potencial instrumento na cicatrização de úlceras crônicas.

Effect of Brazilian green propolis in chronic ulcer treatment: a randomized clinical trial.

to assess the effectiveness of 5% Brazilian green propolis (ointment) in individuals with chronic ulcers. a randomized clinical trial, developed with 40 patients randomized equally to control group (treated with essential fatty acid) and experimental group (treated with 5% green propolis) for 30 days. The outcomes of interest were sociodemographic, clinical and laboratory characteristics, lesion characteristics, such as type of tissue in the bed, presence of exudate, edge characteristics, microbial content and pain. regarding sociodemographic, clinical and laboratory characteristics, the two groups did not show statistically significant differences. After assessment in 30 days, an effect was observed for both treated groups, but for the experimental group, greater effectiveness in terms of the type of tissue in the bed, type of exudate, edge characteristics, microbial content and pain. propolis-based ointment showed a healing effect, presenting itself as a potential tool in healing chronic ulcers.

PHARMACOLOGICAL ACTIVITIES OF BRAZILIAN GREEN PROPOLIS: A NARRATIVE REVIEW

Introduction. Propolis is one of the products made by bees and its chemical composition depends on the region, available plant species and climatic conditions. Among the 13 types of propolis produced in Brazil, green, red and brown are the main ones. Objective. To present the pharmacological properties of Brazilian green propolis observed through experiments involving animals and humans. Methodology. Careful research of articles published from 2017 to 2022 was conducted at Pub-Med, Science direct, Embase and Scielo, focusing on the pharmacological effects of Brazilian green propolis or its constituents observed in clinical trials. Results and discussion. Published results suggest that short- or long-term administration of propolis does not cause toxic effects. Pharmacokinetic studies show that terpenes, such as artepillin C and drupanin, are the main active constituents. Conclusion. For decades the Brazilian green propolis pe used in the treatment and prevention of diseases. However more specific studies are suggested to clarify the pharmacokinetics of green propolis, to establish safe and more effective doses.

Brazilian green propolis prevent Alzheimer’s disease-like cognitive impairment induced by amyloid beta in mice

BackgroundThe increasing incidence of cognitive impairment has become a health problem in the aging society. Owing to its antioxidant and anti-inflammatory properties, Brazilian green propolis—derived from Baccharis dracunculifolia—is anticipated to possess anticognitive properties. However, the preventive effect of Brazilian green propolis on cognitive impairment remains unexplained. This study aimed to investigate the effect of Brazilian green propolis on cognitive impairment using a mouse model of Alzheimer’s disease (AD) induced by intracerebroventricular injection of amyloid beta (Aβ)25‒35.MethodsFive-week-old male Slc:ddY mice were randomly divided into five groups (n = 8). The groups were pretreated with vehicle and propolis at a dose of 100, 300 and 900 mg/kg body weight for 8 days, then AD-like phenotypes were induced by intracerebroventricular (ICV) injection of Aβ25‒35. A sham operation group was set as the control. Memory and learning ability were measured at 7 to 8 days after ICV injection. Gene expression and histological studies were performed at the endpoint of the study.ResultsIn a passive avoidance test, the administration of Brazilian green propolis prevented the impairment of learning and memory function. Furthermore, comprehensive gene expression analysis in the hippocampus and forebrain cortex revealed that Brazilian green propolis suppressed Aβ25–35-induced inflammatory and immune responses. In particular, Brazilian green propolis prevented alterations in gene expressions of microglial and astrocytic markers such as Trem2 and Lcn2 induced by Aβ25‒35 injection, suggesting the suppression of excessive activation of glial cells in the brain. In addition, Brazilian green propolis suppressed the elevation of plasma interleukin (IL)-6 levels induced by Aβ25‒35 injection.ConclusionsThe results suggest that the prophylactic administration of Brazilian green propolis has a preventive effect against AD by suppressing excessive inflammation and immune response in glial cells. To our knowledge, this study is the first to demonstrate that Brazilian green propolis may inhibit the hyperactivation of microglia and astrocytes as a mechanism of action to prevent AD. Thus, it is a promising ingredient for preventing AD-type dementia.

Perspectives on the Role of P21-Activated Kinase 1 (PAK1) in the Intestinal Anti-inflammatory and Antitumor Potential of Artepillin C.

The Brazilian biodiversity may bring new perspectives to the therapy of Inflammatory Bowel Diseases (IBD) and intestinal cancer. The effect of Brazilian Green Propolis in reducing ulcerative colitis in mice has already been described, as well as high amounts of the prenylated compound Artepellin C (ARC). The search for new pharmacological targets for IBD is also advancing. Among possibilities is the p21-activated kinase (PAK1), overexpressed and activated in the intestinal mucosa during IBD and colitis-associated colorectal cancer (CAC). PAK 1 contributes to tissue inflammation by reducing the expression of peroxisome proliferator-activated receptor type γ (PPAR47) and increasing activation of nuclear factor (NF)-κB. At least in vitro, inhibition of PAK1 has been reported to mitigate NF-κB-mediated inflammation in intestinal cells and ARC inhibits PAK1 activation. Given this pharmacological potential of ARC and the role of PAK1 in IBD and CAC, this perspective collected information that encourages future research to test the hypothesis that ARC can maintain intestinal integrity under the inflammatory and neoplastic stimulus and that inhibition of PAK1/NF-κB signaling and favoring PPAR-γ activity is pivotal in this action. Therefore, future studies employing in vitro and in vivo steps, using murine and human enterocytes and rodents submitted to ulcerative colitis and CAC models are incentivized by the data gathered here, favor retirar essas palavras: mostly in vitro studies, before clinical trials. Therefore, the perspective presented here points to an interesting path in the search for a drug useful in inflammatory and neoplastic intestinal diseases, which may have ARC as a prototype, acting on a target not yet explored clinically.

Leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation in a pre-clinical model.

Leishmaniasis is a widespread group of neglected vector-borne tropical diseases that possess serious therapeutic limitations. Propolis has been extensively used in traditional medical applications due to its range of biological effects, including activity against infectious agents. Here we evaluated the leishmanicidal and immunomodulatory properties of Brazilian green propolis extract (EPP-AF®) and a gel formulation incorporating EPP-AF®, in both in vitro and in vivo models of Leishmania amazonensis infection. Propolis extract, obtained from a standardized blend following hydroalcoholic extraction, showed the characteristic fingerprint of Brazilian green propolis as confirmed by HPLC/DAD. A carbopol 940 gel formulation was obtained containing propolis glycolic extract at 3.6% w/w. The release profile, assessed using the Franz diffusion cell protocol, demonstrated a gradual and prolonged release of p-coumaric acid and artepillin C from the carbomer gel matrix. Quantification of p-coumaric acid and artepillin C in the gel formulation over time revealed that p-coumaric acid followed the Higuchi model, dependent on the disintegration of the pharmaceutical preparation, while artepillin C followed a zero-order profile with sustained release. In vitro analysis revealed the ability of EPP-AF® to reduce the infection index of infected macrophages (p < 0.05), while also modulating the production of inflammatory biomarkers. Decreases in nitric oxide and prostaglandin E2 levels were observed (p < 0.01), suggesting low iNOS and COX-2 activity. Furthermore, EPP-AF® treatment was found to induce heme oxygenase-1 antioxidant enzyme expression in both uninfected and L. amazonensis-infected cells, as well as inhibit IL-1β production in infected cells (p < 0.01). ERK-1/2 phosphorylation was positively correlated with TNF-α production (p < 0.05), yet no impact on parasite load was detected. In vivo analysis indicated the effectiveness of topical treatment with EPP-AF® gel alone (p < 0.05 and p < 0.01), or in combination with pentavalent antimony (p < 0.05 and p < 0.001), in the reduction of lesion size in the ears of L. amazonensis-infected BALB/c mice after seven or 3weeks of treatment, respectively. Taken together, the present results reinforce the leishmanicidal and immunomodulatory effects of Brazilian green propolis, and demonstrate promising potential for the EPP-AF® propolis gel formulation as a candidate for adjuvant therapy in the treatment of Cutaneous Leishmaniasis.

Clinical Assessment of Antimicrobial Effects of Brazilian Green Propolis on Chronic Wounds

Pharmacognosy Research,2022,14,3,251-255.DOI:10.5530/pres.14.3.36Published:July 2022Type:Original ArticleAuthors:Pascalle Sousa Rocha, Fernando Luiz Affonso Fonseca, David Feder, Luiz Elidio Gregório, Joserlan Nonato Moreira, Luis Rafael Leite Sampaio, Glaucia Luciano da Veiga, Fulvio Alexandre Scorza, Beatriz da Costa Aguiar Alves, Thais Gascón, Carla Alessandra Scorza, and Fabio Ferreira Perazzo Author(s) affiliations:Pascalle Sousa Rocha1,3, Fernando Luiz Affonso Fonseca2,7, David Feder7, Luiz Elidio Gregório2, Joserlan Nonato Moreira3, Luis Rafael Leite Sampaio4, Glaucia Luciano da Veiga7, Fulvio Alexandre Scorza5,6, Beatriz da Costa Aguiar Alves7, Thais Gascón7, Carla Alessandra Scorza5,6, Fabio Ferreira Perazzo1,2 1Departamento de Morfologia e Fisiologia, Centro Universitário FMABC. Santo André, BRASIL. 2Departamento de Ciências Farmacêuticas. Universidade Federal de São Paulo. Diadema, BRASIL. 3Departamento de Saúde. Instituto Federal da Paraíba. Paraíba, BRASIL. 4Departamento de Enfermagem. Centro de Ciências Biológicas e da Saúde, Universidade Regional do Cariri. Paraíba, BRASIL. 5Centro de Neurociências e Saúde, Universidade Federal de São Paulo /UNIFESP. São Paulo, BRASIL. 6Disciplina de Neurociência. Universidade Federal de São Paulo/UNIFESP. São Paulo, BRASIL. 7Laboratório de Análises Clínicas. Centro Universitário FMABC. Santo André, BRASIL. Abstract:Objectives: Chronic wounds in patients of several diseases, especially diabetics, comprise a public health problem in Brazil. The aim of this study was evaluate the effects of topical application of 5% green propolis ointment on nonspecific chronic wounds of patients from a health unit in Cajazeiras, Paraíba. Materials and Methods: The patients were divided into two groups: 20 for the intervention group, treated with 5% green propolis ointment, and 20 participants for the control group, treated with an essential fatty acid, plus vitamins A and E, which has standard application in the Brazilian Public Service, both during 30 days. The following clinical variables were observed: complications (necrosis, crust), aspects of the skin around the lesion, appearance and amount of exudate, signs of infection, presence of pain during treatment, appearance of any complication and odor. Forty participants were surveyed from May 2017 to October 2018. Results: Most of them were women (52.5%) aging from 76 to 95 years (55%), and illiterate (77.5%). The prevalent bacteria in the wounds were Pseudomonas aeruginosa, and most of the sensitive antibiotics were aminoglycoside. In the control group, two of eight participants evaluated on the first day remained infected, whereas, in the group treated with green propolis ointment, all nine patients had infection cleared, with reduction of pain, 81.8% decrease of lesions with purulent exudate, and 73.4% debridement of devitalized tissue. Conclusion: These results confirm the potential of the green propolis ointment as a debridement, bactericide, and the ability to inhibit the growth of microorganisms, and adsorb odors. Keywords:Chronic wound, Clinical trial, Propolis, Treatment, Wound infectionView:PDF (148.9 KB)

Abstract 5201: Enhanced production of IL-2 from anti CD3-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis

Abstract Objectives: It has been reported that Brazilian green propolis (BGP) possesses anti-tumor and chemo-preventive properties against prostate cancer (Szliszaka E, 2011). And bioactive components from propolis have been shown to have anti-cancerous effects upon hepatocellular carcinoma (Liu X, 2021). These observations revealed that propolis can be an anti-cancer drugs, however the immunological effects upon tumor microenvironments of these naturally occurring components has not been elucidated. In this report, we attempt to clarify immune modulatory effects of BGP and the major component, artepillin C, by observing cytokine production from activated T cells. Methods: The mouse spleen cell stimulated by anti-CD3 monoclonal antibody were co-cultured with BGP, artepillin C and HC030031, an antagonist of TRPA1 Ca2+ channel. The productions of IFN-γ, IL-6, IL-17, IL-4, IL-10 and IL-2 was assayed by ELISA. Results: Our results demonstrated the production of IL-2 was markedly enhanced, while the production of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6 and IL-17 were markedly reduced, in the highly viable stimulated spleen cells treated with BGP. These effects were also reproduced in the cells treated with artepillin C, a major component of BGP. The enhancement of IL-2 production by artepillin C was significantly alleviated by adding 10 HC030031, an antagonist of TRPA1 Ca2+ channel, suggesting the enhancement of the cytokine production by artepillin C could be mediated by Ca2+ influx. Conclusions: The artepillin C, a major component of BGP, is an important regulator of activated T lymphocytes and specifically augmented the expression of IL-2 vie Ca2+-permeable cation channel, TRPA1. These effects may exert immunomodulatory effects upon tumor microenvironments. Citation Format: Nobuo Kondoh, Masako Kamiya, Hanemi Tsuruta, Moe Takahashi, Kumiko Ikeno, Kyohei Ueno, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Genjiro Nakamura, Toru Nikaido, Yasunori Muramatsu, Megumi Ando. Enhanced production of IL-2 from anti CD3-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5201.

Enhanced production of IL-2 from anti-CD3 antibody-stimulated mouse spleen cells by artepillin C, a major component of Brazilian green propolis

ObjectivesIn this report, we attempt to clarify the immune modulatory effects of Brazilian green propolis (BGP) and its major component, artepillin C, on the cytokine production of anti-CD3 antibody-stimulated mouse spleen cells. We also estimate the physiological mechanism affecting artepillin C's upon the cells. MethodsMale C3H/HeN mouse spleen cells stimulated by antiCD3 monoclonal antibody were co-cultured with BGP, artepillin C, and HC030031, a transient receptor potential ankyrin 1 (TRPA1) Ca2+ channel antagonist. The synthesis of interferon (IFN)-γ, interleukin (IL)-6, IL-17, IL-4, IL-10, and IL-2 was assayed by enzyme-linked immunoassay. The expression of IL-2 mRNA and the protein product were examined by reverse transcription-quantitative polymerase chain reaction and Western blot analyses, respectively. ResultsThe production of IL-2 was markedly enhanced, while that of IL-4 and IL-10 was not significantly affected; by contrast, the production of IFN-γ, IL-6, and IL-17 was significantly reduced in the antibody-stimulated spleen cells treated with BGP at a non-cytostatic concentration. These effects were reproduced in the cells treated with artepillin C. The expression of IL-2 mRNA was unaffected; however, that of the protein was significantly enhanced in the artepillin C-treated cells compared to untreated control cells. The enhancement of protein expression and the production of IL-2 by artepillin C was significantly alleviated by adding HC030031. ConclusionsArtepillin C is an important regulator of cytokine synthesis from activated spleen cells. The agent specifically augmented the expression of IL-2 via the Ca2+-permeable cation channel, TRPA1, at least in part, at the translational or secretion levels.

Daily Brazilian green propolis intake elevates blood artepillin C levels in humans.

Propolis is a natural product collected by worker bees from a variety of plant species. As a type of propolis, Brazilian green propolis contains a large amount of artepillin C. Artepillin C is a cinnamic acid derivative and has been shown to have a wide variety of biological functions, including anti-inflammatory, antiviral and antitumor activities, in both cell culture and animal models. However, how propolis is digested and absorbed remains to be elucidated. Moreover, blood artepillin C levels after propolis intake have not been shown in human studies. A randomized, single-blind placebo-controlled study on the effect of Brazilian green propolis on serum artepillin C levels was conducted with healthy volunteers. The participants (n=133) were randomly allocated in an approximately 2:1 ratio to two groups: propolis (n=91) and placebo (n=42). The participants took daily propolis or placebo, and blood tests were performed on day 0 (before propolis intake) and days 1, 3 and 7. Artepillin C was detected in serum in almost all individuals in the propolis groups. No serum artepillin C was detected in the placebo group. Serum artepillin C levels in the female group tended to be higher than those in the male group. In the female group, menstrual status was unrelated to serum artepillin C levels. These results suggested that propolis intake might be more effective for females than for males. © 2021 Society of Chemical Industry.

Effects of Brazilian green propolis extract on planktonic cells and biofilms of multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa

Propolis could represent an alternative therapeutic agent for targeting multidrug-resistant bacteria due to its antimicrobial potential. The effect of Brazilian green propolis (BGP) aqueous extract (AqExt) was evaluated on eight multidrug-resistant clinical strains of Klebsiella pneumoniae and Pseudomonas aeruginosa, as well as on one reference strain for each bacterial species. The minimum bactericidal concentration (MBC) was determined and optimal concentrations were further evaluated in comparison with 0.12% chlorhexidine. The natural extract was chemically characterized by HPLC-DAD analysis. The MBC values ranged between 3.12 and 27.5 mg ml−1. Analysis of bacterial metabolic activity after treatment for 5 min with BGP-AqExt revealed a strong antimicrobial potential, similar to chlorhexidine. The extract comprised several active compounds including quercetin, gallic acid, caffeic and p-coumaric acid, drupani, galangin, and artepillin C. Altogether, the findings suggest that BGP-AqExt is fast and effective against multidrug-resistant strains of K. pneumoniae and P. aeruginosa in planktonic cultures and biofilms.

P1574EFFECTS OF BRAZILIAN GREEN PROPOLIS EXTRACT (EPP-AF) ON INFLAMMATION IN HEMODIALYSIS PATIENTS

Abstract Background and Aims End-stage chronic kidney disease is associated with the condition of chronic inflammation, impacting increased cardiovascular mortality in this specific population. Patients on hemodialysis are known to be predisposed to several factors that predispose to inflammation: dialysis membranes, central venous catheters, oxidative stress, fluid overload, sodium overload, uraemic toxins. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties. The aim of this study was to evaluate the impact of Brazilian green propolis extract on inflammation in hemodialysis patients. Here we present preliminary results of the trial NCT04072341. Method We performed a prospective trial, open-label 9-week crossover study examining the effect of Brazilian green propolis (250mg/day, in capsules) on inflammation in hemodialysis patients. We included patients over 18 years, under intermittent hemodialysis (thrice per week), on hemodialysis for at least 1 month and until now 37 patients were included. We excluded pregnant women, cancer carried and patients who developed infection or underwent any surgical procedure during the study period. Each period was 4 weeks in duration with a 1-week washout period in between. The primary end point was change in serum level of high-sensitivity c-reactive protein (HsCRP). Secondary end point evaluated the safety of propolis use in hemodialysis patients. Results Their mean age was 58.6 ± 15.2 years (mean ± SD), and 22 (59.4%) were men. The proportion of patients with hypertension was 14 (37.8%) and diabetes was 9 (24.3%). The number of patients using arteriovenous fistula were 26 (70.2%). The HsCRP presented (mean ± SE) 5.31 ± 1.02 mg/L at baseline, 4.26 ± 0.76 mg/L after propolis period and 4.56 ± 1.32 mg/L in control period, p = 0.0042. Safety parameters were analyzed such as amylase, aspartate aminotransferase (AST) and creatine phosphokinase (CPK); there was no difference between them before and after the use of propolis. None of the participants reported any adverse effects or allergic reactions during the treatment. Conclusion Patients on hemodialysis have an increased inflammatory state. For the best of our knowledge it was the first clinical trial who demonstrated the safety of propolis in hemodialysis patients. Brazilian green propolis demonstrated a tendency to reduce inflammation in these patients.

Neuroprotective Effect of Brazilian Green Propolis on Retinal Ganglion Cells in Ischemic Mouse Retina

ABSTRACT Purpose The current study was undertaken to investigate whether Brazilian green propolis (BGP) can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and examined the possible mechanisms underlying this neuroprotection. Materials and Methods C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to establish retinal ischemia-reperfusion injury. Mice then received saline or BGP (200 mg/kg) intraperitoneally once daily until sacrifice. The expression of hypoxia-inducing factor (HIF)-1α and glial fibrillary acidic protein (GFAP) and the level of histone acetylation were assessed at 1, 3, and 7 days after injury. The expression of Bax, Bcl-2, p53, NF-κB, Nrf2, and HO-1 were also analyzed at 3 days after injury. The neuroprotective effect of BGP treatment on RGC survival was evaluated using Brn3a immunohistochemical staining. Results The expression of HIF-1α and GFAP was increased and the level of histone acetylation decreased in saline-treated ischemic retinas within 7 days. BGP treatment effectively attenuated the elevated expression of HIF-1α, GFAP, Bax, NF-κB and p53. The expression of Bcl-2, Nrf2, HO-1 and the level of histone acetylation increased by BGP treatment, resulting in a significant difference between BGP-treated and saline-treated retinas. Immunohistochemical staining for Brn3a also revealed that BGP treatment protected against RGC loss in ischemic retina. Conclusions Our results suggest that BGP has a neuroprotective effect on RGCs through the upregulation of histone acetylation, downregulation of apoptotic stimuli, and suppression of NF-κB mediated inflammatory pathway in ischemic retina. These findings suggest that BGP is a potential neuroprotective agent against RGC loss under oxidative stress.

Neuroprotective effects of Brazilian green propolis on oxytosis/ferroptosis in mouse hippocampal HT22 cells

Propolis is a sticky dark-colored substance produced by honey bees and comprises resin, balsam, wax, essential and aromatic oils, pollen, and several other substances; it is used in food and beverages to improve health and prevent diseases. We studied the neuroprotective effects of extracts of Brazilian green propolis in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis had a more potent preventive effect on oxidative stress-induced cell death, oxytosis/ferroptosis, in HT22 cells than water extracts of Brazilian green propolis, whereas it did not protect against anticancer drug-induced apoptotic cell death. Among the primary constituents of ethanol extracts of Brazilian green propolis, only artepillin C, kaempferide, and kaempferol demonstrated neuroprotective effects against oxytosis/ferroptosis. The flavonoid derivatives kaempferide and kaempferol are antioxidants with radical-scavenging abilities that additionally induce antioxidant response element-mediated transcriptional activity, suggesting that upregulation of endogenous antioxidant defense protects against oxidative stress. In contrast, artepillin C attenuated reactive oxygen species production; however, it did not induce antioxidant response element activation. These findings indicate that the ethanol extracts of Brazilian green propolis help to prevent oxidative stress-related neuronal cell death that is involved in the pathogenesis of several neurodegenerative diseases.

Brazilian Green Propolis Inhibits Ox-LDL-Stimulated Oxidative Stress in Human Umbilical Vein Endothelial Cells Partly through PI3K/Akt/mTOR-Mediated Nrf2/HO-1 Pathway

Propolis has been widely used as a dietary supplement for its health benefits, including cardiovascular protective effects. The aim of this study was to investigate the cytoprotective effects of Brazilian green propolis (BP) against oxidized low-density lipoprotein (Ox-LDL) induced human umbilical vein endothelial cells (HUVECs) damage. Our results suggested that treatment with BP rescued Ox-LDL-stimulated HUVECs cell viability losses, which might be associated with its inhibitive effects on the cell apoptosis and autophagy. We also noticed that BP restored Ox-LDL-stimulated HUVECs oxidative stress, by induced antioxidant gene expressions, including Heme oxygenase-1 and its upstream mediator, Nrf2, which were mediated by the activation of the phosphorylation of PI3K/Akt/mTOR. Pretreatment with wortmannin, PI3K/AKT inhibitor, abolished BP induced Nrf2 nuclear translocation and HO-1 level. Our results demonstrated that BP protected HUVECs against oxidative damage partly via PI3K/Akt/mTOR-mediated Nrf/HO-1 pathway, which might be applied into preventing Ox-LDL mediated cardiovascular diseases.

Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial

BackgroundChronic kidney disease (CKD) is a public health problem worldwide, and proteinuria is a well-established marker of disease progression in CKD patients. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties, as well as having been shown to have an antiproteinuric effect in experimental CKD. The aim of this study was to evaluate the impact of Brazilian green propolis extract on proteinuria reduction and the changes in the estimated glomerular filtration rate (eGFR).MethodsThis was a randomized, double-blind, placebo-controlled study including patients with CKD caused by diabetes or of another etiology, 18–90 years of age, with an eGFR of 25–70 ml/min per 1.73 m2 and proteinuria (urinary protein excretion > 300 mg/day) or micro- or macro-albuminuria (urinary albumin-to-creatinine ratio > 30 mg/g or > 300 mg/g, respectively). We screened 148 patients and selected 32, randomly assigning them to receive 12 months of Brazilian green propolis extract at a dose of 500 mg/day (n = 18) or 12 months of a placebo (n = 14).ResultsAt the end of treatment, proteinuria was significantly lower in the propolis group than in the placebo group—695 mg/24 h (95% CI, 483 to 999) vs. 1403 mg/24 h (95% CI, 1031 to 1909); P = 0.004—independent of variations in eGFR and blood pressure, which did not differ between the groups during follow-up. Urinary monocyte chemoattractant protein-1 was also significantly lower in the propolis group than in the placebo group—58 pg/mg creatinine (95% CI, 36 to 95) vs. 98 pg/mg creatinine (95% CI, 62 to 155); P = 0.038.ConclusionsBrazilian green propolis extract was found to be safe and well tolerated, as well as to reduce proteinuria significantly in patients with diabetic and non-diabetic CKD.Trial Registration.(ClinicalTrials.gov number NCT02766036. Registered: May 9, 2016).

Effect of Brazilian green propolis on microorganism contaminants of surface of Gorgonzola-type cheese.

Blue cheeses are susceptible to yeast and bacterial growth on their surface, which causes spoilage during ripening process and the formation of slime. The dairy industry frequently control the proliferation of undesirable microorganisms with natamycin and high salt concentration. The green propolis is a complex of substances that presents antimicrobial properties with great potential as preservative in the food industry. The aims of the present study were to identify the mesophilic aerobic microorganisms present on the surface of Gorgonzola-type cheese, evaluate the antifungal and antibacterial effects of the ethanol extract of green propolis (EEP) on the development of those microorganisms and verify the effects of EEP on the sensory quality of cheese. Ten yeast species belonging to genera Yarrowia, Candida, Debaryomyces and Saccharomyces were identified, as well as seven species of bacteria belonging to genera Staphylococcus, Bacillus, Enterococcus, Corynebacterium and Proteus. The EEP showed minimum biocide concentration (MBC), between 0.3% (weight/weight) and 5% for Bacillus cereus and Proteus vulgaris, respectively. Saccharomyces cerevisiae was the most sensitive species (MBC of 0.63%) and Candida parapsilosis the most resistant one (MBC of 5%). In the sensory analysis, the cheeses involved with EEP at 5% concentration did not differ from the control, while at 10%, there was a slight decrease in acceptance. The EEP has potential and feasibility to be used in Gorgonzola-type cheese, inhibiting the main bacteria and yeasts without affecting largely the sensory characteristics of the product.

Evaluation of Preventive Effects of Brazilian Green Propolis on Equine Herpes Virus 9-Induced Acute Encephalitis

In this study, we aimed to evaluate the preventive effects of Brazilian green propolis on equine herpes virus (EHV)-induced encephalitis in a hamster model. We first investigated the antiviral activity of Brazilian green propolis against EHV-9, and then, examined the effects of propolis on the kinetics and production of cytokines. Sixtyfive male, Syrian hamsters were divided into two treatment groups and control group. The 1st group is a control. The second group was infected intranasally with 50 μl of EHV-9 [3 × 104 plaque-forming units (pfu)] without propolis treatment. The third group received propolis at 500 mg/kg of ethanol extract of Brazilian green propolis by a gavage for 7 days, followed by intranasal inoculation with 50 μl of EHV-9 (3 × 104 pfu). Pre-treatment with propolis was not effective in preventing EHV-9-induced encephalitis via intranasal route. This speculation is supported by similar clinical signs and similar immunohistochemistry based on viral antigen distribution in the brain of infected hamsters in groups 2 and 3 from 3rd day post inoculation (dpi). There were significant increases in cerebral mRNA levels of IL-2, IL-10, and IFN-𝛾 after propolis administration in the propolis-treated group before and after EHV-9 challenge compared with the control non-treated group. In conclusion, Brazilian green propolis showed no obvious effect on the prevention of acute EHV-9-induced acute encephalitis in a hamster model, despite its immune-enhancing activity.

The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. The purpose of this study was to clarify effects of brazilian green propolis and the active ingredient against ALS-associated mutant copper-zinc superoxide dismutase (SOD1)-mediated toxicity. Ethanol extract of brazilian green propolis (EBGP) protected N2a cells against mutant SOD1-induced neurotoxicity and reduced aggregated mutant SOD1 by induction of autophagy. Kaempferide and kaempferol, the active ingredients of EBGP, also inhibited mutant SOD1-induced cell death and reduced the intracellular mutant SOD1 aggregates. Both kaempferide and kaempferol significantly suppressed mutant SOD1-induced superoxide in mitochondria. Western blot analysis showed that kaempferol potentially induced autophagy via the AMP-activated protein kinase (AMPK) - the mammalian target of rapamycin (mTOR) pathway. These results suggest that EBGP containing the active ingredient against mutant SOD1-mediated toxicity is a promising medicine or health food for prevention and treatment of ALS.

The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells.

Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer's disease (AD). We have found that Brazilian green propolis (propolis) improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF), and activity-regulated cytoskeleton-associated protein (Arc), the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS) derived from mitochondria and 8-oxo-2′-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker) but significantly reversed the fibrillar β-amyloid and IL-1β-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K). These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging.