Bioactive compounds of peanut skin in prevention and adjunctive treatment of chronic non-communicable diseases.

The global prevalence of cancer continues to increase, so does its mortality. Strategies that can prevent/treat this condition are therefore required, especially low-cost and low-toxicity strategies. Bioactive compounds of plant origin have been presented as a good alternative. In this scenario, due to its abundant polyphenolic content (around 60 to 120 times greater than that of the grain), peanut skin by-products stand out as a sustainable source of food bioactives beneficial to human health. Investigated studies highlighted the importance of peanut skin for human health, its phytochemical composition, bioactivity and the potential for prevention and/or adjuvant therapy in cancer, through the advanced search for articles in the Virtual Health Library (VHL), Science direct and the Mourisco platform of the FioCruz Institute, from 2012 to 2022. Using the keywords, "peanut skin" AND "cancer" AND NOT "allergy", the words "peanut testa" and "peanut peel" were included replacing "peanut skin". 18 articles were selected from Plataforma Mourisco, 26 from Science Direct and 26 from VHL. Of these, 7 articles evaluated aspects of cancer prevention and/or treatment. Promising benefits were found in the prevention/treatment of chronic non-communicable diseases in the use of peanut and peanut skin extracts, such as cholesterolemia and glucose control, attenuation of oxidative stress and suppressive action on the proliferation and metabolism of cancer cells.

Effects of Branched-Chain Amino Acids on the Inflammatory Response Induced by LPS in Caco-2 Cells.

Branched-chain amino acids (BCAA) are essential for maintaining intestinal mucosal integrity. However, only a few studies have explored the role of BCAA in the modulation of intestinal inflammation. In this study, we investigated in vitro effects of BCAA on the inflammatory response induced by lipopolysaccharide (LPS) (1 µg/mL) in Caco-2 cells. Caco-2 cells were assigned to six groups: control without BCAA (CTL0), normal BCAA (CTL; 0.8 mM leucine, 0.8 mM isoleucine, and 0.8 mM valine); leucine (LEU; 2 mM leucine), isoleucine (ISO; 2 mM isoleucine), valine (VAL; 2 mM valine), and high BCAA (LIV; 2 mM leucine, 2 mM isoleucine, and 2 mM valine). BCAA was added to the culture medium 24 h before LPS stimulation. Our results indicated that BCAA supplementation did not impair cell viability. The amino acids leucine and isoleucine attenuated the synthesis of IL-8 and JNK and NF-kB phosphorylation induced by LPS. Furthermore, neither BCAA supplementation nor LPS treatment modulated the activity of glutathione peroxidase or the intracellular reduced glutathione/oxidized glutathione ratio. Therefore, leucine and isoleucine exert anti-inflammatory effects in Caco-2 cells exposed to LPS by modulating JNK and NF-kB phosphorylation and IL-8 production. Further in vivo studies are required to validate these findings and gather valuable information for potential therapeutic or dietary interventions.

Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications. / Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais.

BACKGROUND: While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. OBJECTIVE: To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. METHODS: Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. RESULTS: The RBC n-6/n-3 ratio was associated with increased LDL(-) (ß = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (ß = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (ß = -1.032; 95% CI = -1.585 - -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. CONCLUSION: RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

FUNDAMENTO: Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. OBJETIVO: Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. MÉTODOS: Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. RESULTADOS: A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (ß = 4,064; IC de 95% = 1,381 ­ 6,748) e sdLDL-c (ß = 1,905; IC de 95% = 0,863 ­ 2,947), e redução do tamanho das partículas de LDL (ß = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. CONCLUSÃO: O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk. / Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular.

BACKGROUND: Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. OBJECTIVE: To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. METHODS: Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. RESULTS: Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. CONCLUSION: Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

FUNDAMENTO: Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. OBJETIVOS: Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. MÉTODOS: Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos ­ lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) ­ e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. RESULTADOS: O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. CONCLUSÃO: O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.

In Vitro Digestion of Peanut Skin Releases Bioactive Compounds and Increases Cancer Cell Toxicity.

Peanut skin is a rich source of bioactive compounds which may be able to reduce the risk factors associated with metabolic syndromes. This study aimed to characterize bio-compounds from peanut skin (Arachis hypogaea) and their bioactivity (antioxidant activity, inhibition of lipase, and carbohydrase enzymes) and to evaluate their anti-proliferative properties in colorectal cancer cells (HCT116) upon in vitro digestion. Peanut skin was digested in two sequential phases, and the final content, named phase-1 (P1) and phase-2 (P2) extracts, was evaluated. Several bioactive compounds were positively identified and quantified by liquid chromatography, including quinic acid, released especially after in vitro digestion. The total phenolic content and, regardless of the method, the antioxidant activity of P1 was higher than P2. P1 also showed a lower enzyme inhibitory concentration IC50 than P2, lipase, and α-glucosidase. For cell viability in HCT116 cells, lower concentrations of P1 were found for IC50 compared to P2. In conclusion, bioactive compounds were released mainly during the first phase of the in vitro digestion. The digested samples presented antioxidant activity, enzyme inhibitory activity, and cancer cell cytotoxicity, especially those from the P1 extract. The potential applications of such a by-product in human health are reported.

Concentration and potential health risk of polycyclic aromatic hydrocarbons for consumers of chocolate in Brazil.

Chocolate is widely consumed worldwide and its market grows every year, with emerging demands for new high-quality products. However, this product is susceptible to contamination with polycyclic aromatic hydrocarbons (PAHs), representing a risk for humans. In this study, a methodology for the evaluation of benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene and chrysene in chocolate by high performance liquid chromatography was validated. The occurrence, dietary exposure, and health risks of 4 PAHs in 38 commercial chocolate samples was investigated. The methodology demonstrated adequate accuracy and precision, with recovery (95.25 %-108.12 %) and relative standard deviation (0.14 %-5.83 %). Benzo[a]pyrene and the ∑4 PAHs concentrations varied between 1.09 and 10.42 µg/kg and 8.38-41.58 µg/kg, respectively. The results of risk assessment suggest low potential health risk for chocolate consumers, considering the margin of exposure (MOE) and the incremental life cancer risk (ILCR) values.

Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais / Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications

Resumo Fundamento Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. Objetivo Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. Métodos Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (β = 4,064; IC de 95% = 1,381 - 6,748) e sdLDL-c (β = 1,905; IC de 95% = 0,863 - 2,947), e redução do tamanho das partículas de LDL (β = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. Conclusão O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Abstract Background While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. Objective To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. Methods Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. Results The RBC n-6/n-3 ratio was associated with increased LDL(-) (β = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (β = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (β = -1.032; 95% CI = -1.585 − -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. Conclusion RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

Ácido Esteárico (mas não o Ácido Palmítico) está Associado a Biomarcadores Inflamatórios e de Disfunção Endotelial em Indivíduos em Risco Cardiovascular / Stearic Acid, but not Palmitic Acid, is Associated with Inflammatory and Endothelial Dysfunction Biomarkers in Individuals at Cardiovascular Risk

Resumo Fundamento Vários estudos têm associado o consumo de ácidos graxos saturados (AGSs) com risco cardiovascular, mas ainda existem muitas controvérsias. A maioria desses estudos avaliou os efeitos do ácido palmítico sobre lipídios circulantes. O ácido esteárico geralmente apresenta um efeito neutro sobre os lipídios sanguíneos, mas faltam estudos clínicos avaliando sua relação com marcadores de inflamação e de disfunção endotelial. Objetivos Avaliar a associação de AGSs das hemácias (ácido palmítico e ácido esteárico) com biomarcadores inflamatórios e de disfunção endotelial circulantes. Métodos Estudo transversal que incluiu 79 adultos de ambos os sexos com pelo menos um fator de risco cardiovascular, mas sem eventos prévios (infarto agudo do miocárdio ou acidente vascular cerebral). Biomarcadores plasmáticos - lipídios, marcadores glicometabólicos, proteína C ultrassensível (PCR-us), Interleucina 6 (IL-6), Interleucina 10 (IL-10), Fator de Necrose Tumoral-α (TNF-α), Proteína quimioatraente de Monócitos 1 (MCP-1) - e ácidos graxos das hemácias (ácidos palmítico e esteárico) foram analisados. As associações foram avaliadas por análises de correlações e regressões lineares múltiplas, com significância estatística estabelecida em p<0,05. Resultados O ácido palmítico não apresentou associações com fatores de risco cardiovasculares ou com marcadores inflamatórios. Por outro lado, o ácido esteárico foi inversamente correlacionado com PCR-us, IL-6 e TNF-α, mas independentemente associado com PCR-us, IL-6, e TNF-α. Conclusão O ácido esteárico está associado com biomarcadores inflamatórios e disfunção endotelial em indivíduos com um ou mais fatores de risco cardiovascular.

Abstract Background Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers. Objective To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers. Methods Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05. Results Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α. Conclusion Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.

Effect of guarana seed powder on cholesterol absorption in vitro and in Caco-2 cells.

Cardiovascular disease risk is related to oxidative stress and hypercholesterolemia. Guarana seed powder contains flavanols that possess antioxidant properties and cholesterol-lowering effects. However, the molecular mechanism through which guarana seed powder may decrease cholesterol uptake from the intestinal lumen remains unclear. Thus, this study aimed to investigate the effect of guarana powder aqueous extract on cholesterol absorption mechanisms. After simulated gastrointestinal digestion, we performed assays to determine enzymatic inhibitory capacity, bile acid binding capacity, and cholesterol micellar solubilization. Caco-2 cells were used for permeation and protein identification assays. Digested guarana powder extract inhibited pancreatic lipase in a dose-dependent manner (half-maximal inhibitory capacity: 1.033 µg/mL) and, at a concentration of 1 mg/mL, bound 45.63 % of sodium taurocholate and decreased cholesterol micellar solubilization by 10.14 %. Moreover, incubation with the extract reduced cholesterol absorption by Caco-2 cells and decreased intracellular cholesterol transporter levels. These results indicate that guarana seed powder have potential applications for blood cholesterol management, presenting hypocholesterolemic effects owing to the presence of bioacessible polyphenols.

Vitamin C and Phenolic Antioxidants of Jua (Ziziphus joazeiro M.) Pulp: A Rich Underexplored Brazilian Source of Ellagic Acid Recovered by Aqueous Ultrasound-Assisted Extraction.

Jua (juá in Portuguese) is an underexplored fruit from Brazil's northeast. This fruit is rich in antioxidant substances. However, there is a dearth of information about jua's bioactive potential. The present study evaluated two extraction methods (continuous agitation and ultrasound-assisted extraction-UAE) and employed three different solvents (water, ethanol, and acetone) to efficiently recover soluble phenolic compounds. Aqueous extracts obtained by UAE showed the highest total phenolic content (TPC) and antiradical activity. Besides being an eco-friendly procedure, extraction and/or solubility in an aqueous medium is also important for food application. Ellagic acids were the predominant phenolics (80%) found in aqueous jua pulp extract obtained by UAE, as determined by HPLC, while its TPC was 405.8 gallic acid equivalent per gram of fruit. This extract also exhibited a higher scavenging activity towards peroxyl radicals when compared to that of several other fruits from the literature, including grape, strawberry, cranberry, and walnuts, which are known references in terms of antioxidants. This is the first report that demonstrates jua pulp's potential as an alternative source of ellagic acid and other phenolic acids and flavonoids. Therefore, the outcome of this study provides new information that can be useful for functional food and nutraceutical industries.

Omega-3 Fatty Acids in Erythrocyte Membranes as Predictors of Lower Cardiovascular Risk in Adults without Previous Cardiovascular Events.

Background: This study investigated the association of omega-3 polyunsaturated fatty acids (n-3 PUFA) within erythrocyte membranes and cardiovascular risk assessed by three different estimates. Methods: Inclusion criteria were individuals of both sexes, 30 to 74 years, with at least one cardiovascular risk factor, and no previous cardiovascular events (n = 356). Exclusion criteria were individuals with acute or chronic severe diseases, infectious diseases, pregnant, and/or lactating women. Plasma biomarkers (lipids, glucose, and C-reactive protein) were analyzed, and nineteen erythrocyte membrane fatty acids (FA) were identified. The cardiovascular risk was estimated by Framingham (FRS), Reynolds (RRS), and ACC/AHA-2013 Risk Scores. Three patterns of FA were identified (Factor 1, poor in n-3 PUFA), (Factor 2, poor in PUFA), and (Factor 3, rich in n-3 PUFA). Results: Total cholesterol was inversely correlated with erythrocyte membranes C18:3 n-3 (r = -0.155; p = 0.004), C22:6 n-3 (r = -0.112; p = 0.041), and total n-3 (r = -0.211; p < 0.001). Total n-3 PUFA was associated with lower cardiovascular risk by FRS (OR = 0.811; 95% CI= 0.675-0.976). Regarding RRS, Factor 3 was associated with 25.3% lower odds to have moderate and high cardiovascular risk (OR = 0.747; 95% CI = 0.589-0.948). The ACC/AHA-2013 risk score was not associated with isolated and pooled FA. Conclusions:n-3 PUFA in erythrocyte membranes are independent predictors of low-risk classification estimated by FRS and RRS, which could be explained by cholesterol-lowering effects of n-3 PUFA.

The anticholesterol oxidation effects of garlic (Allium sativum L.) and leek (Allium ampeloprasum L.) in frozen fish burgers submitted to grilling.

This study determined the total phenolic content and antioxidant capacity of garlic (Allium sativum L.) and leek (Allium ampeloprasum L.), as well as evaluated their anticholesterol oxidation potential in fish burgers. The total phenolic contents were 1.1 ± 0.1 mg GAE/g FW to garlic and 1.3 ± 0.4 mg GAE/g FW for leek. Leek extract showed antioxidant activity index (1.3 ± 0.01) in DPPH and ß-carotene/linoleic acid assay (66.5 ± 1.6%); however, in ORAC assay, no statistic differences were observed (P > 0.05). Besides that, bioactive compounds of garlic and leek extracts were identified by ultra-high performance liquid chromatography-electrospray by ionization-mass spectrometry (UHPLC-ESI-MS). Fish burgers were prepared using different concentrations of leek and garlic and stored at -18 °C for 90 days. Thus, at days 0, 30, 60, and 90, the samples were grilled and analyzed as to their cholesterol and cholesterol oxidation products contents. Storage and grilling led to an increase in cholesterol oxidation products; however, addition of garlic and leek minimized cholesterol oxidation products formation. After 90 days, samples containing 3% leek + 0.5% garlic ware the most effective in inhibiting the cholesterol oxides formation during storage and showed the lowest increase in cholesterol oxidation products content (21.16%). Thus, the findings of this research indicate the potential application of garlic and leek as natural inhibitors of cholesterol oxidation in food. PRACTICAL APPLICATION: Garlic and leek have a set of bioactive compounds with a wide antioxidant capacity when used in meat foods such as fish burgers. Garlic and leek used as natural antioxidants perform well in the shelf life of fish burgers and can be substitutes for synthetic antioxidants in this type of product. The presence of both vegetables reduced the formation of prejudicial products to human health generated during the shelf life of the food.

Identification and action of phenolic compounds of Jatobá-do-cerrado (Hymenaea stignocarpa Mart.) on α-amylase and α-glucosidase activities and flour effect on glycemic response and nutritional quality of breads.

This study investigated the phenolic profile of jatobá-do-cerrado (Hymenaea stignocarpa Mart.) extracts submitted to in vitro digestion, the inhibition of α-amylase and α-glucosidase activities; and the effect of jatobá-do-cerrado flour addition on the nutritional quality, glycemic index (GI) and acceptability of breads. The phenolic composition was determined by UPLC-MS. Bread formulations were developed adding the jatobá-do-cerrado flour at 10, 20 and 30% (w/w) to replace wheat flour. Phenolic compounds of biological relevance such as caffeic acid, kaempferol, quercetin-3-rutinoside and quercetin-3-rhamnoside were present in jatobá-do-cerrado. The phenolic extracts after in vitro digestion significantly inhibited the α-amylase and α-glucosidase activities. Breads with 20% jatobá-do-cerrado flour addition promoted significant reduction (22%) in GI from 70 (control) to 54.3, while 30% addition presented GI of 57.4 and 10% addition a GI of 62.5. The replacement of refined wheat flour by jatobá-do-cerrado flour reduced glycemic response of breads in a non-dose dependent manner. The dietary fibers and the phenolic compounds of jatobá-do-cerrado exerted a synergetic modulation of glucose metabolism by inhibiting sugar metabolic enzymes and glucose absorption. Thus, jatobá-do-cerrado can be included in the diet of healthy individuals and chronic diseases patients, such as diabetics, as an alternative to improve glycemic control.

Peptides from Chia Present Antibacterial Activity and Inhibit Cholesterol Synthesis.

In previous studies, it has not been reported that protein isolated from chia interferes favorably with antibacterial activity, and reduces cholesterol synthesis. The objective of this study was to determine whether commonly used commercial microbial proteases can be utilized to generate chia protein-based antibacterial and hypocholesterolemic hydrolysates/peptides, considering the effects of protein extraction method. Alcalase, Flavourzyme and sequential Alcalase-Flavourzyme were used to produce hydrolysates from chia protein (CF), protein-rich fraction (PRF) and chia protein concentrates (CPC1 and CPC2). These hydrolysates were evaluated for their antimicrobial activity against Gram-positive (G+) and Gram-negative (G-) microorganisms. The protein hydrolysates were purified by ultrafiltration through a membrane with 3 kDa nominal molecular weight, for evaluation of hypocholesterolemic activity. An inhibition zone was observed when the hydrolysate was tested against S. aureus, and minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were obtained. Peptides from chia protein with molecular mass lower than 3 kDa reduced up to 80.7% of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) enzymatic reaction velocity. It was also observed that, independent of the method used to obtain chia proteins, the fractions showed relevant bioactivity. Moreover, the intensity of the bioactivity varied with the method for obtaining the protein and with the enzyme used in the hydrolysis process. This is the first report to demonstrate that chia peptides are able to inhibit cholesterol homeostasis.

Avaliação de biodisponibilidade e mecanismos de ação hipocolesterolemizante de peptídeos do amaranto (Amaranthus cruentus L. BRS-Alegria) / Evaluation of bioavailability and hypocholesterolemic mechanisms of peptides from Amaranth (Amaranthus cruentus L. BRS-Alegria)

Introdução: Doenças cardiovasculares constituem importante causa de morte em todo mundo e a hipercolesterolemia está diretamente relacionada a este problema de saúde pública. A dieta desempenha papel importante neste processo e alguns alimentos, como o amaranto (Amaranthus cruentus L. BRSAlegria), têm mostrado capacidade de redução do colesterol plasmático. Estudos sugerem que este efeito está relacionado a peptídeos liberados durante a digestão das proteínas, os quais atuam na modulação do metabolismo lipídico. Considerando-se que os efeitos da digestão gastrointestinal e da absorção destes peptídeos são claramente complexos torna-se importante a realização de estudos visando avaliar bioacessibilidade e mecanismos de ação destes peptídeos nos locais alvo do organismo. Objetivo: Analisar a biodisponibilidade de peptídeos em modelos animais após ingestão de isolado proteico de amaranto e relacioná-la com parâmetros ligados ao metabolismo do colesterol. Métodos: O amaranto teve sua proteína isolada. Os peptídeos da proteína do amaranto foram analisados após digestão in vitro. Dois experimentos in vivo foram conduzidos: um de fase aguda e outro de média duração. No primeiro, o isolado proteico de amaranto foi administrado a ratos e os peptídeos no sangue foram monitorados por 2 horas para verificação de fragmentos que resistissem à digestão gastrointestinal. O experimento in vivo 2 consistiu na alimentação de 3 grupos de hamster, um com dieta recomendada pela AIN93 (grupo N) e dois com dietas hipercolesterolêmicas por 21 dias, contendo a proteína de amaranto como única proteína da ração (grupo I), comparada ao controle de caseína (grupo H). Neste experimento foram analisados no plasma: peptídeos, colesterol total e frações; nas fezes: colesterol total e ácidos biliares; no fígado: colesterol, lipídeos totais, ácidos graxos, atividade enzimática da Hmgcr, expressão de Hmgcr, Srebf2, Lxr, Abca1, Abcg8 e Ampk. Resultados e discussão: Foram identificados fragmentos peptídicos provenientes da digestão in vitro do isolado proteico de amaranto, e outras dezenas de sequencias peptídicas em ratos após administração aguda de amaranto foram analisadas. Destaca-se a identificação do peptídeo ALGV, presente em proteína do amaranto de acordo com banco de dados, e similar a fragmentos com ação hipocolesterolemizante. No sangue de hamsters foram encontrados seis peptídeos com 100 por cento de cobertura e similaridade a base de dados de proteínas de amaranto, merecendo investigação sobre seus efeitos. Verificou-se que o isolado proteico de amaranto foi capaz de suprimir a hipercolesterolemia quando a dieta hipercolesterolemizante foi introduzida em paralelo a este ingrediente, com valores inferiores em 72 por cento (triglicerídeos), 64 por cento (colesterol total), 80 por cento (LDL-c) do grupo I em relação ao grupo H. Foi observada ainda menor concentração de colesterol e lipídeos totais no fígado dos animais do grupo I em relação ao grupo H (177 x 464 mg de colesterol/100 g de tecido; 2,06 x 2,86 g de lipídeos/100 g de tecido, respectivamente). Parâmetros lipídicos do sangue, das fezes e do fígado foram similares aos do grupo N, cuja dieta seguiu a preconização para roedores. Foi observada maior excreção de colesterol total no grupo I em relação ao grupo H, mas não houve maior excreção de ácidos biliares nas fezes. Não houve mudança na expressão dos genes analisados neste estudo, mas o amaranto reduziu a atividade da enzima Hmgcr. Postulase que parâmetros como expressão de Ldlr e atividade da Acat sejam alterados pela ingestão de amaranto. O perfil de ácidos graxos também foi modificado de forma a se assimilar ao grupo N, porém deve-se verificar parâmetros inflamatórios devido à maior proporção de ácido araquidônico em relação aos demais grupos estudados. Conclusão: Verifica-se biodisponibilidade dos peptídeos do amaranto e ação hipocolesterolemizante e hipolipemiante em diversas vias metabólicas, promovendo proteção cardiovascular

Introduction: Cardiovascular diseases are important causes of death worldwide, and hypercholesterolemia is directly related to this public health problem. Diet plays an important role in this process and some foods such as amaranth (Amaranthus cruentus L. BRS-Alegria) have been shown to reduce plasma cholesterol. Studies suggest that this effect is related to peptides released during the digestion of proteins, which would play an important role in the modulation of lipid metabolism. Considering that the effects of gastrointestinal digestion and the absorption of these peptides are clearly complex, it is important to carry out studies aiming to evaluate their bioaccessibility and evaluation of the mechanisms of action of these peptides in the target sites of the organism. Objective: To analyze the bioavailability of peptides in animal models after ingestion of amaranth protein isolate and to relate it to parameters associated to cholesterol metabolism. Methods: The amaranth was crushed, the flour was defatted and its protein isolated. Amaranth peptides were analysed after in vitro digestion. Two in vivo experiments were conducted: one of acute phase and one of medium duration. In the first, the amaranth protein isolate was administered to rats and the peptides in the blood were monitored for 2 hours to check for fragments that resisted gastrointestinal digestion. The in vivo experiment 2 consisted of feeding three groups of hamsters, one with a diet recommended by AIN93 (group N) and two with hypercholesterolemic diets for 21 days, containing amaranth protein as the only dietary protein (group I), compared to casein control (group H). In this experiment were analyzed in the plasma: peptides, total cholesterol and fractions; In feces: total cholesterol and bile acids; In the liver: cholesterol, total lipids, fatty acids, Hmgcr enzymatic activity, Hmgcr expression, Srebf-2, Lxr, Abca1, Abcg8 and Ampk. Results and discussion: Peptide fragments from the in vitro digestion of amaranth protein isolate were identified and other dozens of peptide sequences were found in rats after acute amaranth administration. A higher number of peptides were found in the serum in relation to the plasma of the animals. Remarkably, ALGV peptide was found in serum of rats. This peptide is present in amaranth protein, according to databases, and is similar to fragments that present hypocholesterolemic action. In the blood of hamsters it could be found six peptides with 100 per cent coverage and similarity to the database of amaranth proteins, deserving investigation about their effects. Amaranth protein was able to suppress hypercholesterolemia when the hypercholesterolemic diet was introduced in parallel with this ingredient, with values lower for group I in 72 per cent (triglycerides), 64 per cent (total cholesterol), 80 per cent (LDL-c) in relation to the H group. A lower concentration of cholesterol and total lipids were observed in the liver of the group I compared to the H group (177 x 464 mg cholesterol / 100 g of tissue, 2.06 x 2,86 g lipids / 100 g of tissue, respectively). Lipid parameters of blood, faeces and liver were similar to those of group N, whose diet followed the recommendation for rodents. There was greater excretion of total cholesterol in group I in relation to group H, but there was no greater excretion of bile acids in feces, indicating that the effect of amaranth protein may be due to increased transintestinal cholesterol excretion, decreased micellar solubilization of cholesterol and / or modification in the expression of cholesterol transport related proteins in the intestine. There was no change in the expression of the genes analyzed in this study, but amaranth reduced the activity of the Hmgcr enzyme. It is postulated that parameters such as Ldlr expression and Acat activity are altered by amaranth intake. The fatty acid profile was also modified in order to assimilate to the N group, but inflammatory parameters related to amaranth intake should be verified due to the higher proportion of arachidonic acid in relation to the higher proportion of arachidonic acid in relation to the other groups studied. Conclusion: The bioavailability of amaranth peptides and hypocholesterolemic and hypolipidemic activity in several metabolic pathways is verified, therefore promoting cardiovascular protection

Peptides from cowpea present antioxidant activity, inhibit cholesterol synthesis and its solubilisation into micelles.

In previous studies, it was reported that the protein isolated from the cowpea interferes favourably in lipid metabolism, and reduces cholesterol synthesis. The present study investigated the role of cowpea peptide fractions in the micellar solubilisation of cholesterol, in the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) activity, and in the in vitro antioxidant capacity, considering the effects of thermal processing. The protein was isolated from the raw and cooked beans and digested to simulate human digestion. The peptides from the protein isolate of raw bean with molecular mass lower than 3kDa reduced 89% of the HMGCR enzymatic reaction velocity. The cooked cowpeas were more effective in inhibiting the micellar solubility of cholesterol than the raw ones but not the antioxidant activity. This is the first report that cowpea peptides inhibit cholesterol homeostasis in vitro in two distinct routes, and act as an antioxidant.

Apoptosis induction by (+)alpha-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells.

We analyzed the effect of (+)alpha-tocopheryl succinate (alpha-TOS) alone or associated with arsenic trioxide (ATO) or all-trans retinoid acid (ATRA) in acute promyelocytic leukemia (APL). alpha-TOS-induced apoptosis in APL clinical samples and in ATRA-sensitive (NB4) and ATRA-resistant (NB4-R2) APL cell lines. The effective dose 50% (ED-50) was calculated to be 71 and 58muM, for NB4 and NB4-R2, respectively. alpha-TOS neither induced nor modified ATRA-induced differentiation of APL cells, and did not affect the proliferation and differentiation of normal CD34(+) hematopoietic progenitors in methylcellulose assays. alpha-TOS exerted a moderate antagonistic effect to ATO-induced apoptosis when treatment was done simultaneously but when alpha-TOS was added 24h after ATO, an additive effect was observed. Our results support the concept of alpha-TOS as an anti-leukemic compound which spares normal hematopoiesis.