Emerging Roles of Propolis: Antioxidant, Cardioprotective, and Antiangiogenic Actions

Propolis has attracted attention in recent years due to its beneficial effects, which make it a potential preventive and therapeutic agent as well as a useful additive in food and cosmetics. The aim of this review is to discuss the growing evidence that propolis may, via a diverse array of biological actions, assist in the prevention of some inflammation-mediated pathologies including cardiovascular disease. The active components of propolis that have been identified so far include polyphenols and flavonoids. These compounds have cardioprotective, vasoprotective, antioxidant, antiatherosclerotic, anti-inflammatory and antiangiogenic actions. Many studies have been undertaken to elucidate the mechanism(s) by which propolis acts, which involve cellular signaling targets and interactions at the genomic level. This review will highlight the effects of propolis that may assist in the prevention of chronic degenerative diseases, such as cardiovascular disease

Jaboticaba (Myrciaria jaboticaba) powder consumption improves the metabolic profile and regulates gut microbiome composition in high-fat diet-fed mice

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity.This work was financially supported by Brazilian funding: FAPERJ – Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ: E-26/202.677/2018, E-26/010.002203/2019) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES) – Finance code 001. Benjamin Willing was supported by the Canada Research Chair Program and his laboratory received funding from the Canadian Natural Science and Engineering Research Council (NSERC

Avaliação da qualidade nutricional de duas variedades de soja e a influência de seu consumo nos indicadores de doenças cardiovasculares em ratos senis

The organism s aging process promotes morphophysiological alterations that lead to diseases including those related to the cardiovascular system. Nutrition has a great influence in this process, and it is a consensus that the consumption of soybean can act as a protection factor in preventing these diseases. The objective of this study was to evaluate the nutritional quality of two varieties of soybean (organic and genetically modified) as well as the influence their consumption has and their functional properties in cardiovascular disease indicators. Thirty rats were used, divided into 3 groups (n = 10): GC-casein-based ration; GO-organic soybean-based ration; GG-genetically modified soybean-based ration. They all received water and rations ad libtum throughout the entire period. For the preparation of the rations, the centesimal composition of the raw substances and the constituent of the rations were carried through, as well as the concentrations of isoflavones of the rations, that were isocaloric and isoproteic. Data were collected on weight, ration consumption and protein three times per week to determine PER and IC. At the end of 455 days, the animals were sacrificed to determine the seric concentrations of cholesterol, triglycerides, hematocrit, hemoglobin, total proteins and albumin (BIOCLIN Kits), insulin and glucose (Gold Analiza Kits). A segment of the aorta was also removed to determine tunic and heart thickness. Grade M-42 was used to check the collagen s area (Vvi(i%)) in the left ventricle. Both tissues were fixed in Milong formalin and underwent processing until coloration, when images were taken for subsequent analysis. The Kruscal-Walis test was applied to the results at a p&#8804; 0.05 level using S-Plus R 1.5 Version 6.0 software. We observed that the soybeans used in the experiment were similar and that the rations had the same composition of macro-nutrients as well as isoflavones. After 28 days of the experiment the GO s PER was higher (p<0.00008) than the GG s, and GC s was higher than both. On the 291st day we observed that the IC of the soybean-based group (GO and GG) were similar to GC, which was also observed on the 455th day. At the end of the experiment, the hematocrit (p<0.04) and hemoglobin (p<0.03) levels were lower in the soybean-based groups compared to the GC. The values for total proteins, albumin and insulin showed no difference among the groups. The cholesterol (p<0.0001), triglyceride (p<0.0072) and glucose (p<0.0013) data were lower in GO and GG compared to GC. The histology revealed that the endothelium in the GO and GG groups were lower (p<0.0095) than the GC, however they presented the same amount of collagen in the left ventricle. We concluded that both soybeans were effective in replacing animal protein in the phase that encompasses senility and no differences were revealed in the two varieties. The soybean also proved to be an important alternative for the prevention of cardiovascular disease.Conselho Nacional de Desenvolvimento Cientifico e TecnológicoO processo de envelhecimento do organismo promove alterações morfofisiológicas que propiciam o aparecimento de doenças, dentre elas as relacionadas ao sistema cardiovascular. A alimentação exerce grande influência neste processo, sendo consenso que o consumo de soja pode agir como um fator protetor na prevenção destas doenças. O objetivo desse estudo foi avaliar a qualidade nutricional de duas variedades de soja (orgânica e geneticamente modificada) bem como a influência do seu consumo e de suas propriedades funcionais nos indicadores de doenças cardiovasculares. Foram utilizados 30 ratos, divididos em 3 grupos (n=10), sendo: GC-recebendo ração à base de caseína; GO- recebendo ração à base de soja orgânica; GG- recebendo ração à base de soja geneticamente modificada. Todos consumiram água e rações ad libtum durante todo o período. Para o preparo das rações foi realizada a composição centesimal das matérias primas e dos constituintes das rações, assim como as concentrações de isoflavonas das rações, sendo as rações isocalóricas e isoprotéicas. Foram coletados dados de peso, consumo de ração e de proteína 3x por semana para determinar o Protein Efficacy Ratio (PER) e o Índice de Crescimento (IC). Ao final de 455 dias, os animais foram sacrificados para a determinação das concentrações séricas de colesterol total, triglicerídeos, hematócrito, hemoglobina, proteínas totais e albumina (Kits da BIOCLIN) , insulina e glicose (Kits da Gold Analiza). Retirou-se ainda um segmento da aorta, para determinação da espessura das túnicas e do coração, para aferição da área ocupada por colágeno (Vvi(i%)) existente no ventrículo esquerdo, para tal utilizou-se a grade M-42. Ambos os tecidos foram fixados em formalina de Millonnig e sofreram processamento até a coloração, onde logo foram capturadas imagens para posterior análise. Aos resultados aplicou-se o teste de Kruskal-Wallis ao nível de p&#8804; 0,05 através do software S-Plus Versão 6.0. Observou-se que as sojas utilizadas para o experimento possuíam composição centesimal semelhantes e que as rações ofertadas tinham o mesmo percentual de macronutrientes assim como teor semelhante de isoflavonas. Aos 28 dias de experimento o PER do GO foi superior (p<0,00008) ao GG, sendo o GC superior a ambos. Já no 291° o IC dos grupos a base de soja (GO e GG) foram semelhantes ao GC, o mesmo foi observado no 455° dia. Ao final do experimento, as concentrações de hematócrito (p<0,04) e hemoglobina (p<0,03) foram inferiores nos grupos à base de soja, em relação ao GC. Já os valores de proteínas totais, albumina e insulina não tiveram diferença entre os grupos.Os dados de colesterol (p<0,0001), triglicerideos (p<0,0072) e glicose (p<0,0013) foram inferiores no GO e no GG comparados ao GC. As túnicas da aorta dos grupos GO e GG foram inferiores (p<0,0095) ao GC, no entanto apresentavam a mesma quantidade de colágeno no ventrículo esquerdo. Concluiu-se que ambas as sojas foram eficazes na substituição da proteína animal na fase que compreende a senilidade não apresentando diferenças entre as duas variedades. A soja mostrou-se como uma importante alternativa para a prevenção de doenças cardiovasculares

Anti-angiogenic activity and modulation of protein-involved in new vases formation by propolis bioactive compounds

Rica em compostos bioativos, a própolis é amplamente utilizada na medicina alternativa como agente preventivo e/ou terapêutico. Neste trabalho, avaliamos o impacto de frações ricas em polifenóis de diferentes própolis no processo de angiogênese na aterosclerose. Foram utilizadas as seguintes amostras de própolis: Red (vermelho, Alagoas-Brasil), Green (verde, Minas Gerais-Brasil) e Brown (marrom, Temuco-Chile), com concentrações semelhantes de polifenóis totais (~32%), porém com diferentes perfis de compostos fenólicos. A suplementação (250 mg/Kg/dia) de camundongos knockout para o receptor de LDL (LDLr-/-) com os polifenóis demonstrou que no protocolo de lesão inicial (LI) os grupos suplementados apresentaram menor (p<0,05) área de lesão (Green, 726&#181;m2; Red, 519&#181;m2; Brown, 698&#181;m2) em relação ao controle (GC, 1184&#181;m2). Em contraste, no protocolo de lesão avançada (LA) apenas o grupo Red (1082&#181;m2) apresentou menor (p<0,05) área de lesão em relação ao GC (1598&#181;m2). Em ambos os protocolos (LI e LA) observou-se redução (p<0,05) na expressão de importantes genes envolvidos no processo de angiogênese (VEGF, MMP9, PDGF e PECAM). No entanto, apenas o grupo tratado com a própolis Red foi capaz de aumentar (p<0,05) a expressão de TIMP-1 no protocolo de LI. Todos os tratamentos inibiram (p<0,05), em cerca de 45%, a migração de células endoteliais (CE), bem como cerca de 55% do brotamento de tubos de anéis de aorta, em relação ao controle e ao redor de 50% da formação de novos vasos na membrana corioalantóica de embrião de galinha (CAM). Ao investigar o mecanismo de ação dos polifenóis, observamos que os polifenóis da própolis Red (PRP) mostraram-se mais eficazes em modular a expressão do Fator induzido por Hipóxia-1 alfa (HIF-1&#945;), de modo dose/tempo dependente em células endoteliais. Adicionalmente, os polifenóis da própolis Red (PRP) reduziram a expressão de genes alvos regulados por HIF-1&#945; como GLUT-1 e ADM, além de inibir a expressão gênica e a secreção de VEGF em meio de cultura. Em presença dos PRP, a degradação de HIF-1&#945; foi exarcebada e, utilizando-se células RCC4/pVHL (células de carcinoma renal com VHL reintroduzido), observou-se que PRP induzem a desestabilização de HIF-1&#945; acelerando sua degradação dependente de pVHL. Em células endoteliais, pVHL foi superexpresso devido à inibição de Cdc42, um repressor de pVHL. Conclui-se que os polifenóis oriundos das própolis Green, Red e Brown possuem potencial anti-aterogênico através da inibição da expressão de moléculas inflamatórias e angiogênicas, principalmente quando suplementados ao início do desenvolvimento da lesão aterosclerótica. Além disso, os polifenóis da própolis Red inibem o processo de angiogênese, aumentando a desestabilização de HIF-1&#945; pelo aumento da degradação via pVHL e induzindo sua expressão em função da repressão de Cdc42.Propolis is rich in bioactive compounds and widely used in alternative medicine as a preventive agent and/or in therapy. We evaluate the impact of polyphenol-rich fractions of propolis from different origins and types in the angiogenesis process in atherosclerotic lesions. The following samples of propolis were used: Red (red, Alagoas, Brazil), Green (green, Minas Gerais, Brazil) and Brown (brown, Temuco, Chile), with similar concentrations of total polyphenols (~ 32%) but with different profiles of phenolic compounds. Supplementation (250 mg / kg / day) of knockout mice for the LDL receptor (LDLr-/ -) with polyphenols showed that in the initial lesion (LI) protocol supplemented groups had lower (p<0.05) lesion area (Green, 726&#181;m2; Red, 519&#181;m2; Brown 698&#181;m2) compared to control (GC, 1184&#181;m2). In contrast, in the advanced lesions (LA) protocol only the Red group (1082&#181;m2) had smaller lesion area (p<0.05) compared to GC (1598&#181;m2). In both protocols (LI and LA) a reduction (p<0.05 of important genes expression involved in angiogenesis (VEGF, MMP9, PDGF and PECAM) was observed. However, only the group treated with Red propolis was able to increase (p <0.05) the expression of TIMP-1 in the LI protocol. The treatments with all types of propolis inhibited (p<0.05), about 45% the migration of endothelial cells (EC), approximately 55% of tubes formation in aortic rings and almost 50% of formation of new vessels in the chorioallantoic membrane of chick embryo (CAM) compared to the control. While investigating the mechanism of polyphenols action, it was found that polyphenols from Red propolis (PRP) were more effective in modulating the expression of hypoxia-induced factor-1 alpha (HIF-1&#945;) in a dose/time dependent way in EC. Additionally, the polyphenols from red propolis (PRP) reduced the expression of target genes regulated by HIF-11&#945; as GLUT-1, ADM, VEGF besides the VEGF protein secretion in the EC culture medium. In the presence of PRP, the degradation of HIF-11&#945; was exacerbated in RCC4/pVHL cells (renal cell carcinoma with VHL reintroduced); moreover, PRP induced destabilization of HIF-11&#945; accelerating the degradation of this transcription factor by a pVHL-dependent patway. In EC, pVHL was over expressed by inhibition of Cdc42, a repressor of pVHL. We conclude that the polyphenols from Green, Red and Brown propolis have anti-atherogenic potential by inhibiting the expression of angiogenic and inflammatory genes, especially when supplemented at an early stage of the atherosclerotic lesion development. In addition, the polyphenols from Red propolis inhibit the angiogenesis process by increasing the destabilization of HIF-11&#945; via over expression of pVHL-degradation induced by repressed Cdc42 function

Evaluation of protein quality from genetically modified and organic soybean in two consecutives generations of wistar rats

The aim of this study was to evaluate the cumulative effects of using genetically modified and organic soybean in two generations of rats. Two consecutive generations of 64 Wistar rats denominated F0 and F1 were used. The animals from each generation were divided into three groups (n=8) and fed chow made of organic soybean, genetically modified soybean and casein. The PER, NPR and CAE were determined. ANOVA was applied to the results. In both the generations, a statistically significant (p<0.05) difference was found between the experimental groups and the control group. The organic soybean supplement with L-cystine provided a better use of this protein in comparison to the genetically modified soybean protein, which demonstrated that the soybean maintained its protein use, although always inferior to casein. Thus, soybean should be used with caution during the growth stages because even with supplements, it remained inferior in relation to the casein group

Activation of Nrf2-Antioxidant Signaling by 1,25-Dihydroxycholecalciferol Prevents Leptin-Induced Oxidative Stress and Inflammation in Human Endothelial Cells

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Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis

International audienceAims: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases.Main methods: The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect.Key findings: Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I2 = 0 %) and decreased the plasma creatinine (SMD-1.24, [-1.59; -0.88], P < 0.0001, I2 = 36.0 %) and urea (SMD-3.22 [-4.42, -2.01], P < 0.0001, I2 = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD-2.20 [-2.68; -1.73], P < 0.0001, I2 = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD-3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis (SMD-2.24 [-2.96; -1.53], P < 0.0001, I2 = 9.7 %) and decreased kidney injury molecular biomarkers (SMD-1.51 [-2.00; -1.02], P < 0.0001, I2 = 0 %).Significance: These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease

Determination of the binding properties of p -cresyl glucuronide to human serum albumin

International audiencep-Cresyl glucuronide (p-CG) is a by-product of tyrosine metabolism that accumulates in patients with end-stage renal disease. p-CG binding to human serum albumin in physiological conditions (37 degrees C, pH 7.40) was studied by ultrafiltration (MWCO 10kDa) and data were analyzed assuming one binding site. The estimated value of the association constant was 2.77x10(3)M(-1) and a maximal stoichiometry of 3.80mol per mole. At a concentration relevant for end-stage renal patients, p-CG was 23% bound to albumin. Competition experiments, using fluorescent probes, demonstrated that p-CG did not bind to Sudlow's site I or site II. The p-CG did not interfere with the binding of p-cresyl-sulfate or indoxyl sulfate to serum albumin

Role of Natural Antioxidants from Functional Foods in Neurodegenerative and Metabolic Disorders

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EVALUATION OF THE INFLUENCE OF THE PROTEINIC QUALITY OF THE GENETICALLY MODIFIED AND ORGANIC SOY BEANS IN THE GROWTH OF TWO GENERATIONS OF RATS WISTAR

Feijo, T.S., Cardozo, SX, Daleprane, J.B., Sabaa Srur, A.U.O. & Boaventura, G.T. [Evaluation of the influence of the proteinic quality of the genetically modified and organic soy beans in the growth of two generations of rats Wistar.] Avaliacao da influencia da qualidade proteica da soja geneticamente modificada e organica no crescimento de duas geracoes de ratos Wistar. Revista Brasileira de Medicina Veterinaria, 31(3):139-144, 2009. Programa de Pos-Graduacao em Patologia, Hospital Universitario Antonio Pedro. Centro de Ciencias Medicas, Universidade Federal Fluminense. Rua Marques do Parana, 303, Niteroi, RJ 24030-210, Brasil. E-mail: [email protected] Sixty four Wistar rats, male of two consecutive generations determined as F(0) and F(1) were used to study the cumulative effect of two variety soy beans, cultivated with organic seasoning and genetically modified, The animals of each generation were divided into three groups of eight rats each fed on diets consisted of organic soy, soy genetically modified and casein respectively. All the animals received water and the diet ad libitum for period of 28 days. Where the diet consumption and the animals weight were evaluated. After statistic analysis of the results no expressive differences were observed on diet consumption, weight variation, protein efficient ratio and food efficiency ratio on same group of animals in the different generations. On the other hand, significant difference was found on final proteinic retention on animal descendants of the same groups; however of different generations. With this, the supplementation of organic soy with L-cistin provided better avail of this protein in relation to the protein of the soy genetically modified. However, this supplementation did not reveal efficiency in keeping the proteinic employment from one generation to another one, since soy varieties presented better performance on F(0) generation when compared with F(1)