Potencial efecto terapéutico de los polifenoles obtenidos de la cáscara de granada en la esteatosis hepática

RESUMEN Antecedentes: La enfermedad por hígado graso no alcohólico (EHGNA) tiene una elevada prevalencia a nivel mundial, y puede ir desde la esteatosis simple hasta hepatocarcinoma. Su origen es multifactorial, siendo la dieta poco saludable un factor clave en su patogenia y progresión. Los polifenoles son antioxidantes que han mostrado beneficios en el tratamiento de la EHGNA. Una fuente emergente de estos compuestos son los residuos agroindustriales, entre ellos, la cáscara de granada. La cáscara de granada tiene un alto contenido de polifenoles, específicamente de elagitaninos. Su extracto fenólico (extracto de cáscara de granada; ECG) ha mostrado efectos promisorios a nivel metabólico. Sin embargo, su uso presenta algunas limitantes que deben ser consideradas antes de recomendar su ingesta mediante alimentos funcionales o nutracéuticos para prevención o tratamiento de EHGNA. Objetivo: Discutir a partir de datos obtenidos en estudios in vitro y modelos animales, el potencial terapéutico de los polifenoles obtenidos de la cáscara de granada para prevención y tratamiento de la EHGNA. Metodología: Se realizó una búsqueda bibliográfica en bases de datos PubMed y Web of Science (2015 a la fecha) de estudios en modelos de esteatosis hepática in vitro y en animales, además de ensayos clínicos relacionados. Conclusión: Existen datos promisorios sobre el uso del ECG en alteraciones metabólicas propias de la EHGNA y esteatosis hepática, principalmente a nivel de perfil lipídico. Se deben discutir las dosis y formas de administración, con el fin de mejorar su estabilidad y biodisponibilidad. Se requieren ensayos clínicos controlados que confirmen los efectos en humanos.

ABSTRACT Background: Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide and can range from simple steatosis to hepatocarcinoma. Its causes are multifactorial, with an unhealthy diet being a key factor in its pathogenesis and progression. Polyphenols are antioxidants that have shown benefits in treating NAFLD. An emerging source of these compounds is agro-industrial by-products, including pomegranate peels. Pomegranate peels are high in polyphenols, specifically ellagitannins. Its polyphenolic extract (PPE) has shown promising metabolic benefits. However, its use has some limitations that must be considered before recommending its intake through functional foods or nutraceuticals to prevent or treat NAFLD. Objective: This article aims to discuss, using results from in vitro studies and animal models, the therapeutic potential of polyphenols obtained from pomegranate peels to prevent and treat NAFLD. Methods: A bibliographic search was carried out in PubMed and Web of Science databases (2015 to date) of in vitro and animal model studies of hepatic steatosis, in addition to related clinical trials. Conclusion: There are promising data on the use of PPE in metabolic disorders typical of NAFLD and hepatic steatosis, mainly improving lipid profile. Doses and vehicles of administration should be discussed to improve stability and bioavailability. Controlled clinical trials are required to confirm the effects in humans.

Ellagic acid production using polyphenols from orange peel waste by submerged fermentation

Background: Biotechnological processes are part of modern industry as well as stricter environmental requirements. The need to reduce production costs and pollution demands for alternatives that involve the integral use of agro-industrial waste to produce bioactive compounds. The citrus industry generates large amounts of wastes due to the destruction of the fruits by microorganisms and insects together with the large amounts of orange waste generated during the production of juice and for sale fresh. The aim of this study was used orange wastes rich in polyphenolic compounds can be used as source carbon of Aspergillus fumigatus MUM 1603 to generate high added value compounds, for example, ellagic acid and other molecules of polyphenolic origin through submerged fermentation system. Results: The orange peel waste had a high concentration of polyphenols, 28% being condensed, 27% ellagitannins, 25% flavonoids and 20% gallotannins. The major polyphenolic compounds were catechin, EA and quercetin. The conditions, using an experimental design of central compounds, that allow the production of the maximum concentration of EA (18.68 mg/g) were found to be: temperature 30°C, inoculum 2 × 107 (spores/g) and orange peel polyphenols 6.2 (g/L). Conclusion: The submerged fermentation process is an effective methodology for the biotransformation of molecules present in orange waste to obtain high value-added as ellagic acid that can be used as powerful antioxidants, antibacterial and other applications.

Polyphenolic content, in vitro antioxidant activity and chemical composition of extract from Nephelium lappaceum L. (Mexican rambutan) husk

Objective To determinate the recovery of total polyphenolic compounds content, in vitro antioxidant activity and HPLC/ESI/MS characterization of extract from Nephelium lappaceum L. (Mexican rambutan). Methods The rambutan husk extract was obtained by aqueous extraction and a polyphenolic fraction was recovered using Amberlite XAD-16. The total polyphenolic compounds content was determined by the Folin Ciocalteu and butanol-HCI methods. In vitro antioxidant activity was performed using ABTS and ferric reducing antioxidant power methods. Results Mexican rambutan husk showed a total polyphenolic content of 582 mg/g and an evident antioxidant activity by ABTS and ferric reducing antioxidant power analysis. The HPLC/ESI/MS assay allowed the identification of 13 compounds, most of which belong to ellagitannins. Geraniin, corilagin and ellagic acid were present in the sample; the mineral composition was also evaluated. Conclusions Rambutan husk cultivated in Mexico is a promising source for the recovery of added value bioactive compounds with antioxidant activity, which have potential applications as bioactive antioxidant agents for the treatment of diseases.

Identification and fragmentation regularity of polyphenol compounds from Galla Quercina by UPLC-MS/MS / 中草药

Objective To explore the fragmentation regularity and identify the polyphenol components in Galla Quercina. Methods Waters Xevo TQD liquid chromatography/mass spectrometer ESI negative mode was used to analysis, mobile phase was 0.02% formic acid-water and acetonitrile for gradient eluent. Data were analyzed by Mass Lynx software. Results Three categories and 15 compounds in Galla Quercina were identified and divided into gallotannins, ellagitannins, and phenolic acids. Gallotannins was cleaved by loss of gallic acyl, C2H2O, CH2O, CO2, and OH, and the gallotannins had the regular loss of gallic acid units (152). Conclusion The results of fragmentation mechanism can be used to detect polyphenol compounds in Galla Quercina and provide a useful reference for the study on the chemical constituents of medicinal plants rich in polyphenols.

Polyphenolic content, in vitro antioxidant activity and chemical composition of extract from Nephelium lappaceum L. (Mexican rambutan) husk

OBJECTIVE@#To determinate the recovery of total polyphenolic compounds content, in vitro antioxidant activity and HPLC/ESI/MS characterization of extract from Nephelium lappaceum L. (Mexican rambutan).@*METHODS@#The rambutan husk extract was obtained by aqueous extraction and a polyphenolic fraction was recovered using Amberlite XAD-16. The total polyphenolic compounds content was determined by the Folin Ciocalteu and butanol-HCI methods. In vitro antioxidant activity was performed using ABTS and ferric reducing antioxidant power methods.@*RESULTS@#Mexican rambutan husk showed a total polyphenolic content of 582 mg/g and an evident antioxidant activity by ABTS and ferric reducing antioxidant power analysis. The HPLC/ESI/MS assay allowed the identification of 13 compounds, most of which belong to ellagitannins. Geraniin, corilagin and ellagic acid were present in the sample; the mineral composition was also evaluated.@*CONCLUSIONS@#Rambutan husk cultivated in Mexico is a promising source for the recovery of added value bioactive compounds with antioxidant activity, which have potential applications as bioactive antioxidant agents for the treatment of diseases.

Efeito de extratos ricos em antocianinas ou elagitaninos de amora silvestre (Morus nigra L. ), amora preta (Rubus spp), e grumixama (Eugenia brasiliensis Lam) no crescimento e na expressão de genes e miRNAs de diferentes linhagens de céluas humanas de câncer de mama / Effects of extracts rich in anthocyanins or ellagitans from mulberry (Morus nigra L. ), blackberry (Rubus spp) and grumixama (Eugenia brasiliensis Lam) on cellular growth and gene and miRNAs expression from distinctive human breast cancer cell lines

O câncer de mama caracteriza-se globalmente como a neoplasia de maior incidência e mortalidade na população feminina. Antocianinas e elagitaninos presentes em frutas como as berries destacam-se por seu promissor efeito protetor em diferentes estágios do desenvolvimento do câncer de mama. Grumixama (G; Eugenia brasiliensis Lam) é uma espécie de cereja nativa do Brasil que assim como as amora-preta (AP; Rubus spp) e silvestre (AS; Morus nigra L.) contém alto teor de antocianinas e elagitaninos. Poucos estudos focaram na ação anticâncer destas berries no câncer de mama. Portanto, o objetivo do presente estudo foi avaliar os efeitos de extratos ricos em antocianinas ou elagitaninos de G, AP e AS no crescimento e na expressão de genes e miRNAs das linhagens de células humanas de câncer de mama MCF-7 (receptor de hormônio positiva) e MDA-MB 231 (receptor de hormônio negativa). Não se observou citotoxicidade após 72 e 96 horas de tratamento com os extratos (25-200µg/mL) ricos em antocianinas (ASANT, APANT e GANT) ou elagitaninos (APELA e GELA), em ambas as linhagens celulares. Após 72 horas de tratamento, GANT e APANT induziram parada de ciclo celular em G0/G1 (12,5 e 50µg/mL, p<0,05) em células MCF-7. Após 96h, ASANT, APANT e GANT induziram parada de ciclo celular em G0/G1 (12,5 e 50µg/mL; p<0,05) nessas mesmas células. Entretanto, na concentração de 200µg/mL apenas GANT induziu parada em G0/G1 (72 e 96h; p<0,05). Em células MDA-MB 231, após 96h APANT e GANT induziram parada de ciclo celular em G0/G1 nas concentrações testadas (12,5, 50 e 200µg/mL, p<0,05), assim como ASANT nas concentrações de 12,5 e 50µg/mL (p<0,05). Em células MCF-7, após 72h APELA e GELA induziram aumento da proporção de células em subG0 (200µg/mL, p<0,05). Em MDA-MB 231, após 72 e 96h, APELA e GELA (200µg/mL) induziram aumento da proporção de células em subG0 (p<0,05) e parada em G0/G1 (p<0,05). Em células MCF-7, GANT induziu morte celular por apoptose (p<0,05) após 72 e 96h de tratamento. Entretanto, em MDA-MB 231 os extratos ricos em antocianinas não induziram morte celular. Em células MCF-7, após 96h GELA e APELA induziram principalmente necrose (p<0,05). Em MDA-MB 231, APELA e GELA induziram apoptose (p<0,05) após 72 e 96h. Em células MDA-MB 231, após 72h de tratamento foi observada inibição da proliferação celular por GELA, GANT e APELA (200µg/mL; p<0,05). Em células MDA-MB 231, 48h de tratamento com GELA; GANT e APELA (200µg/mL) aumentaram a expressão 5 genes (ESR2, FOXA1, JUN, PTGS2,VEGFA) e inibiram a expressão de 10 genes (ADAM23, ATM, BCL2, CDH1, EGF, GLI1, ID1, MKI67, SNAI2 e THBS1) correlacionados ao câncer de mama. Adicionalmente, GELA; GANT e APELA (200µg/mL) induziram aumento da expressão de miR- 210(p<0,05) e APELA (200µg/mL) reduziu a expressão de miRNA 19a/b (p<0,05) em células MDAMB 231. Coletivamente estes resultados sugerem que antocianinas de grumixama e elagitaninos de amora preta e grumixama apresentam potencial efeito protetor contra o câncer de mama. Adicionalmente, essa ação anticarcinogênica pode ser mediada por indução de morte celular, mais especificamente apoptose, redução de proliferação celular e modulação da expressão de genes e miRNAs relacionados ao câncer de mama.

Breast cancer is characterized as the neoplasia with the highest incidence and mortality rates in women worldwide. Anthocyanins and ellagitannins present in certain fruits, such as berries, stand out for their promising protective effect at different stages of breast cancer development. Grumixama (G; Eugenia brasiliensis Lam), a cherry species from Brazil, as well as blackberry (AP; Rubus spp) and mulberry (AS; Morus nigra L.) contain elevated concentrations of anthocyanins and ellagitannins. Few studies focused on the anticarcinogenic action of these berries in breast cancer development. Therefore, the aim of the present study was to evaluate the effects of extracts rich in anthocyanins or ellagitannins from G, AP and AS on cellular growth and genes and miRNAs expression in human MCF-7 (hormone receptor positive) and MDA-MB 231 (hormone receptor negative) cell lines. No cytotoxicity was observed after 72 and 96 hours of treatment with extracts rich in anthocyanin (25-200 µg/mL) (ASANT, APANT and GANT) or ellagitannins (APELA and GELA) in both cell lines. After 72 hours of treatment, GANT and APANT induced cell cycle arrest at G0/G1 (12.5µg/mL and 50µg/mL, p<0.05) in MCF-7 cells. After 96h, ASANT, APANT and GANT induced cycle arrest at G0/G1 (12.5 and 50µg/mL; p<0.05) in MCF-7 cells. However, at 200µg/mL, only GANT induced G0/G1 (72 and 96h; p<0.05). In MDA-MB 231 cells, after 96h APANT and GANT induced cell cycle arrest at G0/G1 with the three tested concentrations (12.5, 50 and 200µg/mL, p<0.05), as well as ASANT at concentrations 12,5 and 50µg/mL (p <0.05). In MCF-7 cells, after 72h APELA and GELA induced an increase in the proportion of cells in subG0 (200µg/mL, p<0.05). In MDA-MB 231, after 72 and 96h, APELA and GELA (200µg/mL) induced an increase in the proportion of cells in subG0 (p<0.05) and cell cycle arrest in G0/G1 (p<0.05). In MCF-7 cells, GANT induced apoptosis (p<0.05) after 72 and 96h of treatment. However, in MDA-MB 231, extracts rich in anthocyanins did not induce cell death. In MCF-7 cells, after 96h GELA and APELA induced mainly necrosis (p<0.05). In MDA-MB 231, APELA and GELA induced apoptosis (p<0.05) after 72 and 96h. In MDA-MB 231 cells, inhibition of cell proliferation by GELA, GANT and APELA (200?g/mL; p<0.05) was observed after 72h of treatment. In MDA-MB 231 cells, treatment for 48h with GELA, GANT and APELA (200µg) increased expression of 5 genes (ESR2, FOXA1, JUN, PTGS2, VEGFA) and inhibited expression of 10 genes (ADAM23, ATM, BCL2, CDH1, EGF, GLI1, ID1, MKI67, SNAI2 and THBS1) correlated with breast cancer. In addition, GELA; GANT and APELA (200µg/mL) induced increased expression of miR-210 (p<0.05) and APELA (200µg/mL) reduced the expression of miRNA 19a/b (p<0.05) in MDA-MB cells 231. Collectively these results suggest that anthocyanins of grumixama and ellagitannins of blackberry and grumixama have potential protective effect against breast cancer. Additionally, this anticarcinogenic action can be mediated by induction of cell death, more specifically apoptosis, reduction of cell proliferation and modulation of the expression of genes and miRNAs related to breast cancer.

Biomarker exposure of phenolic compounds from grumixama (Eugenia brasiliensis Lam. ) in healthy human model: Metabolomic approach / Identificação de biomarcadores de exposição de compostos fenólicos degrumixama (Eugenia brasiliensis Lam. ): Abordagem metabolômica

The fruits and vegetables intake has been associated to the reduction of chronic non-communicable disease incidence, such as cancer, metabolic syndrome and cardiovascular diseases. The biological activities attribute to them has been related mainly to the phenolic compounds, such as flavonoids and ellagitannins, presents in their composition. However, the bioavailability and influence of these compounds under human metabolism still unclear. Thus, the objective of the present study was investigate changes in human metaboloma as a result of the acute intake of the polyphenol-rich source from purple grumixama juice (Eugenia brasiliensis Lam.), searching to identify possible sites of metabolic regulation. In this way, purple and yellow grumixama varieties were characterized to polyphenol profile, and a single dose of the purple grumixama juice was administered to healthy human. The purple grumixama showed be a good source of anthocyanins and ellagitannins, mainly cyanidin 3-O-glucoside and strictinin, respectively. In the clinical trial, 15 healthy subjects intake a single dose of purple grumixama juice (10 ml of juice/kg of body mass). Plasma and urine samples were collected, before and after intake (over 24 h), and analyzed by GC-MS and LC-MS. The exogenous metabolites excreted and identified in urine samples by LC-MS were identified as urolithins and phenolic acids, gut microbiota catabolites of ellagitannins and anthocyanins, respectively. Four urolithins were detected beginning excretion 4 h after juice intake, increasing over 24 h. Furthermore, four phenolic acids were identified, being the hippuric acid the majority of them. 114 metabolites were identified to urine collection points before and after intake (1-2 h and 2-4 h) by CG-MS, being 17 amino acids, 7 other classes, 47 organic acids and 43 unknown compounds. A OPLS-DA discriminated the metabolites changed by the grumixama juice intake. The pathway analysis showed that juice intake influenced mainly three metabolic pathways: glyoxylate and dicarboxylate metabolism (up-regulated), beta-alanine metabolism (down-regulated), and phenylalanine metabolism (up-regulated), being these pathways related to energetic metabolism. Furthermore, the purple and yellow grumixama fruits extracts were evaluated in animal model of obesity and insulin resistance (C57BL/6J mice) induced by high fatty and high sugar diet. The treatment, during 8 weeks, promoted lipid metabolism modulation. As conclusions, purple grumixama showed to be a good source of anthocyanins and ellagitannins, and the interaction among the metabolites from fruits and endogenous metabolites can be related to changes in energetic metabolism and amino acid metabolism. However, more studies are necessary to elucidate and validate these hypotheses

O consumo de frutas e verduras na dieta está associado à redução da incidência de doenças crônicas não transmissíveis entre eles câncer, síndrome metabólica e doenças cardiovasculares. A atividade biológica atribuída à ingestão desses alimentos é relacionada principalmente à presença de compostos bioativos, entre eles os compostos fenólicos, tais como flavonoides e elagitaninos. Contudo, a biodisponibilidade e a influência destes compostos no metabolismo humano não estão estabelecidas. Assim, o objetivo geral do presente estudo foi investigar as alterações no metaboloma humano decorrente da ingestão de uma fonte rica em compostos fenólicos, o suco da grumixama roxa (Eugenia brasiliensis Lam.), buscando identificar possíveis pontos de regulação do metabolismo. Para isto, a grumixama, variedades amarela e roxa, foram caracterizadas quanto ao seu perfil de compostos fenólicos e administradas na forma de suco, em dose única, a voluntários saudáveis. A grumixama roxa se mostrou rica em antocianinas e elagitaninos, principalmente cianidina 3-O-glicosídeo e a strictinina, respectivamente. Para o ensaio clínico, 15 voluntários saudáveis consumiram, em dose única, suco de grumixama roxa (10 ml de suco/kg de peso corporal). Amostras de plasma e urina foram coletadas em diferentes tempos durante 24 h após ingestão e analisados por CG-MS e LC-ESI-MS/MS. Os metabólitos exógenos excretados na urina foram identificados como urolitinas e ácidos fenólicos, derivados da degradação, principalmente, pela microbiota dos elagitaninos e das antocianinas, respectivamente. Quatro urolitinas (A, B, C e D) foram encontradas na urina, principalmente como metabólitos de fase II, detectados a partir de 4 h após a ingestão do suco com aumento na concentração observado até 24h. Além disso, quatro ácidos fenólicos foram identificados, destes o ácido hipúrico como majoritário. 114 metabólitos, entre eles, 17 aminoácidos, 47 ácidos orgânicos, 7 outras classes de compostos e 43 compostos desconhecidos foram identificados por CG-MS, para os tempos de coleta de urina antes da ingestão de suco de grumixama (T0) e para os períodos de 1-2 h e 2-4 h após a ingestão. A OPLS-DA foi utilizada para descriminar os metabólitos alterados pela ingestão de suco de grumixama. A análise das vias metabólicas mostrou que a ingestão do suco de grumixama influenciou principalmente em três vias metabólicas: metabolismo do glioxilato e dicarboxilato (up-regulated), da beta-alanina (down-regulated) e da fenilalanina (up-regulated), sendo essas direcionadas ao metabolismo energético. Além disso, os extratos de grumixama roxa e amarela também foram testados em modelo animal (camundongo C57BL/6J) de obesidade e resistência à insulina induzido por uma dieta rica em lipídeos e açúcares. O tratamento com os extratos, concomitante à dieta e durante 8 semanas, promoveu modulação significativa do metabolismo lipídico. Como conclusões, a grumixama roxa mostrou ser uma boa fonte de antocianinas e elagitaninos, e a interação entre metabólitos oriundos da ingestão do fruto e dos metabólitos endógenos podem estar relacionados com alterações nos metabolismos de aminoácidos e energético. No entanto, mais estudos são necessários para elucidar e validar as hipóteses geradas

Clinical Evaluation of a New-Formula Shampoo for Scalp Seborrheic Dermatitis Containing Extract of Rosa centifolia Petals and Epigallocatechin Gallate: A Randomized, Double-Blind, Controlled Study

BACKGROUND: Scalp seborrheic dermatitis is a chronic type of inflammatory dermatosis that is associated with sebum secretion and proliferation of Malassezia species. Ketoconazole or zinc-pyrithione shampoos are common treatments for scalp seborrheic dermatitis. However, shampoos comprising different compounds are required to provide patients with a wider range of treatment options. OBJECTIVE: This study was designed to evaluate a new-formula shampoo that contains natural ingredients-including extract of Rosa centifolia petals and epigallocatechin gallate (EGCG)-that exert antioxidative, anti-inflammatory, and sebum secretion inhibitory effects, and antifungal agents for the treatment of scalp seborrheic dermatitis. METHODS: Seventy-five patients were randomized into three treatment groups; new-formula shampoo, 2% ketoconazole shampoo, and 1% zinc- pyrithione shampoo. The clinical severity scores and sebum levels were assessed by the same dermatologists at baseline (week 0), and at 2 and 4 weeks after using the shampoo. User satisfaction and irritation were also assessed with the aid of a questionnaire. RESULTS: The efficacy of the new-formula shampoo was comparable to that of both the 1% zinc-pyrithione shampoo and the 2% ketoconazole shampoo. Furthermore, it was found to provide a more rapid response than the 1% zinc-pyrithione shampoo for mild erythema lesions and was associated with greater user satisfaction compared with the 2% ketoconazole shampoo. However, the new-formula shampoo did not exhibit the previously reported sebum inhibitory effect. CONCLUSION: Extract of R. centifolia petals or EGCG could be useful ingredients in the treatment of scalp seborrheic dermatitis.

Caracterização e biodisponibilidade de derivados de ácido elágico da jabuticaba (Myrciaria jaboticaba) / Characterization and bioavailability of ellagic acid derivatives from jaboticaba (Myrciaria jaboticaba)

O ácido elágico é um composto fenólico presente em algumas frutas e sementes. As maiores fontes da dieta humana são as frutas conhecidas como berries, a romã e as nozes. Dentre as frutas nativas brasileira, a jabuticaba apresenta teores de ácido elágico comparáveis aos das berries. Além disso, a jabuticaba representa uma boa fonte de flavonoides e destaca-se pelo sabor apreciado e pelo grande número de frutos que oferece a cada floração. Dessa forma, os objetivos deste trabalho foram: caracterizar duas espécies de jabuticaba, Sabará e Paulista (Myrciaria jaboticaba (Vell.) Berg and Myrciaria cauliflora (Mart.) O. Berg), em diferentes estádios de maturação, assim como as frações polpa, casca e semente, quanto ao teor e perfil de flavonoides, ácido elágico livre e total, elagitaninos, proantocianidinas e capacidade antioxidante in vitro. Ainda, avaliar o efeito da administração de extrato bruto e/ou frações fenólicas da jabuticaba Sabará sobre o status antioxidante e perfil bioquímico de ratos Wistar diabéticos induzidos por estreptozotocina. As frações fenólicas de jabuticaba também foram testados em modelo de prevenção de obesidade e diabetes tipo 2 induzidas por dieta hiperlipídica em camundongos C57 Black 6. Também foi avaliado o efeito de extrato bruto e frações fenólicas da jabuticaba em culturas celulares de hepatócitos FAO, macrófagos J774.1 e músculo L6. A biodisponibilidade de derivados do ácido elágico também foi estudada, tanto em modelo in vitro de fermentação quanto in vivo em ratos Wistar. Os resultados demonstraram que existem diferenças nos teores de compostos bioativos entre as espécies, e entre os estádios de maturação. A variedade Sabará destacou-se em relação à capacidade antioxidante, teor de proantocianidinas e ácido elágico total, e por ser mais cultivada e consumida pela população, foi escolhida para continuar os estudos in vivo. Em culturas celulares, o tratamento com os extratos de jabuticaba foi capaz de inibir a produção de óxido nítrico em macrófagos e hepatócitos, e aumentou a captação de glicose em células musculares. Os animais diabéticos tratados com a jabuticaba apresentaram alterações do perfil lipídico plasmático, com reversão dos altos teores de colesterol total e triacilglicerídeos. Outros efeitos como a redução da peroxidação lipídica e aumento da capacidade antioxidante plasmática também foram observados. No modelo de prevenção de obesidade e diabetes tipo 2, o tratamento com os extratos fenólicos da jabuticaba melhorou a sensibilidade à insulina e a tolerância à glicose, mesmo diante do consumo de dieta hiperlipídica e incremento ponderal dos animais. O estudo da biodisponibilidade mostrou que os derivados do ácido elágico são metabolizados especialmente pela microbiota intestinal e seus derivados foram detectados no plasma, cólon, fígado, rins, músculo e cérebro dos animais. Estes resultados demonstraram que a jabuticaba pode ser considerada uma excelente fonte de compostos bioativos e o seu consumo pode ser associado à prevenção de alterações metabólicas causadas pelo diabetes e obesidade, como a dislipidemia e a resistência à insulina

Ellagic acid is a phenolic compound present in several fruits and nuts. Walnuts and berries are some known sources. Among the Brazilian native fruits, jaboticaba shows ellagic acid content comparable to that of berries. In addition, jaboticaba is a good source of flavonoids and stands out due to its appreciated flavor and the large number of fruits produced in each flowering. In this way, this work aimed to characterize two species of jaboticaba, Sabará and Paulista (Myrciaria jaboticaba (Vell.) Berg and Myrciaria cauliflora (Mart.) O. Berg), in different ripening stages, as well as pulp, skin and seeds, in relation to the content and composition of flavonoids, free and total ellagic acid, ellagitannins, proanthocyanidins and in vitro antioxidant capacity. Besides, evaluate the effect of raw extract and solid-phase purified phenolic fractions from Sabará jaboticaba administration on antioxidante status and biochemical profile in streptozotocin-induced diabetic Wistar rats. The jaboticaba phenolic fractions were also tested on high-fat-diet-induced obesity and type 2 diabetes in C57BL/6 mice. The effect of phenolic fractions on glucose transport in L6 muscle cells and nitric oxide production in FAO hepatocytes and J774 macrophages were also assessed. The bioavailability of polyphenols from jaboticaba were studied using in vitro and in vivo methods. The results indicated that the phenolic compounds contents are different between the two species, and among the different ripening stages. Sabará species presented the highest amounts of proanthocyanidins and total ellagic acid, and the highest antioxidant capacity. For being the most cultivated and consumed, this species was chosen for the in vivo studies. In cell cultures, the jaboticaba extracts inhibited the nitric oxide production in macrophages and hepatocytes, and increased glucose uptake in L6 muscle cells. In streptozotocin induced diabetic animals, treatment with jaboticaba led to improvement in lipid profile, reducing the levels of total cholesterol and triacylglycerol. Reduction in lipid peroxidation and increase in antioxidant capacity were also observed. In high-fat-diet induced diabetic mice, the phenolic fractions improved insulin sensitivity and glucose tolerance, even when mice become obese. The bioavailability study revealed that the ellagic acid derivatives and other jaboticaba polyphenols were metabolized, especially by the colonic microbiota, and their metabolites were detected in plasma, colon, kidneys, liver, brain, muscle, and stomach. These results demonstrated that jaboticaba may be considered an excellent source of bioactive compounds, and its consumption can be related to reduced risk of metabolic disorders caused by diabetes and obesity, such as dyslipidemia and insulin resistance

Influence of foliar nutrients on phenol levels in leaves of Eugenia uniflora

Eugenia uniflora L., Myrtaceae, leaves contain high amounts of phenolic compounds which are responsible for several pharmacological activities. In order to evaluate the phenolics seasonal variation leaves were analysed on a monthly basis during the period of two years for the contents of hydrolysable tannins, total phenols, flavonoids, and nutrients (N, P, K, S, Ca, Mg, Mn, Zn, Cu, and Fe). Results were correlated with climate conditions (rainfall, humidity, and mean temperature) by Principal Component and ClusterAnalysis which allowed four groups to be distinguished with respect to the age of the leaves and the content of some metals. Young leaves were characterised by high levels of Zn and nitrogen whereas old leaves contained high levels of Fe and calcium, and both groups had moderate amounts of phenolics. Adult leaves were divided in two groups and results revealed that while one group had the highest levels of all phenols and lowest amounts of Mn and Cu, the other showed opposite quantities. The Canonical Correlation Analysis confirmed a highly significant negative correlation between phenol contents and Mn and Cu. These facts suggested that flavonoids and tannins production depends of the amounts of foliar nutrients, Cu and Mn in particular, which are cofactors of enzymes involved in phenol degradation and lignin biosynthesis. This knowledge can improve this specie cultivation in order to enhance the phenolic compounds concentration.