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1.
Int J Mol Sci ; 23(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36499253

RESUMO

Previous research showed that canary seed (Phalaris canariensis L.) peptides (CSP) possess robust in vitro antiobesity properties via inhibition of pancreatic lipase (PL). Nevertheless, no studies have yet explored their antiobesity properties in vivo. Consequently, we investigated the effects of CSP in C57BL/6J mice under a Western diet (WD). Mice were assigned into groups and fed a normal diet (ND) or a WD accompanied by an oral dose of CSP (250 or 500 mg/kg/day), orlistat (40 mg/kg/day), or distilled water. The results showed that consuming CSP can provide metabolic benefits, including preventing weight gain by up to 20%, increasing glucose tolerance, and reducing insulin, leptin, and LDL/VLDL levels in plasma. Conversely, total ghrelin was unaffected by CSP-500, but decreased by CSP-250, and amplified by orlistat. Surprisingly, CSP-250 was more effective in preventing weight gain and promoting satiety than CSP-500. Parallel to this, protein absorption in CSP-500 was decreased, supported by a rise in fecal crude protein (+3.5%). Similarly, fecal fat was increased by orlistat (38%) and was unaffected by CSP-250 (3.0%) and CSP (3.0%), comparatively to WD (2.5%). Despite this, both CSP treatments were equally effective in decreasing hepatic steatosis and avoiding hyperlipidemia. Furthermore, the enzymatic analysis showed that CSP-PL complexes dissociated faster (15 min) than orlistat-PL complexes (41 min). Lastly, CSP did not affect expression of hepatic lipid oxidation genes ACO and PPAR-α, but reduced the expression of the hydrolase gene LPL, and lipogenesis related genes FAS and ACC. Taken together, these results suggest that CSP antiobesity mechanism relies on lipid metabolism retardation to increase fat transit time and subsequently suppress hunger.


Assuntos
Intolerância à Glucose , Phalaris , Animais , Camundongos , Dieta Hiperlipídica , Dieta Ocidental , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/prevenção & controle , Intolerância à Glucose/metabolismo , Lipase/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/prevenção & controle , Orlistate/farmacologia , Sementes/metabolismo , Aumento de Peso
2.
J Stroke Cerebrovasc Dis ; 29(4): 104618, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31973907

RESUMO

BACKGROUND: Metabolome profiling is used to identify biomarkers for acute ischemic stroke (AIS). Previous studies compared metabolite profiles in AIS and healthy controls, which did not account for factors that affect metabolome (genetics, medications). This pilot project evaluates the change in metabolite concentrations between the acute and chronic stage of stroke in the same cohort in order to minimize other factors impact. METHODS: We performed global metabolome profile on serum of 20 and urine of 12 stroke patients in acute (72 hours) and chronic (3-5.2 months) stage and compared relative peak values using Wilcoxon and orthogonal partial least squares discriminant analysis methods. Chronic stage metabolite concentrations were considered baseline. We performed analysis to identify significantly overrepresented pathways using MetaboAnalyst. RESULTS: Three serum metabolites asparagine (P = .045), tyrosine (P = .015), and xylose (P = .003) had significantly higher concentrations in acute stage. Seven out of top 10 serum metabolites ranked by Wilcoxon test P value were related to amino acid (AA) metabolism. Two urine metabolites glycine (P = .03) and acetylcarnitine (P = .05) had significantly different concentrations in the acute stage. Five of the top 10 urine metabolites related to AA metabolism. We identified 6 significant pathways after false discovery rate correction that were upregulated in the acute stage: (1) Aminoacyl-tRNA synthesis, (2) nitrogen, (3) alanine, aspartate, and glutamate, (4) branched-chain AA, (5) arginine and proline, and (6) phenylalanine metabolism. CONCLUSION: Longitudinal study design confirms that AA metabolism heavily involved in the pathophysiology of acute brain ischemia. Prospective longitudinal studies with a higher number of participants are needed to establish useful stroke biomarkers.


Assuntos
Aminoácidos/sangue , Aminoácidos/urina , Isquemia Encefálica/diagnóstico , Metabolômica , Acidente Vascular Cerebral/diagnóstico , Doença Aguda , Biomarcadores/sangue , Biomarcadores/urina , Isquemia Encefálica/sangue , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/urina , Doença Crônica , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/urina
3.
Int J Mol Sci ; 20(10)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137777

RESUMO

Ulcerative colitis (UC), which is a major form of inflammatory bowel disease (IBD), is a chronic relapsing disorder of the gastrointestinal tract affecting millions of people worldwide. Alternative natural therapies, including dietary changes, are being investigated to manage or treat UC since current treatment options have serious negative side effects. There is growing evidence from animal studies and human clinical trials that diets rich in anthocyanins, which are pigments in fruits and vegetables, protect against inflammation and increased gut permeability as well as improve colon health through their ability to alter bacterial metabolism and the microbial milieu within the intestines. In this review, the structure and bioactivity of anthocyanins, the role of inflammation and gut bacterial dysbiosis in UC pathogenesis, and their regulation by the dietary anthocyanins are discussed, which suggests the feasibility of dietary strategies for UC mitigation.


Assuntos
Antocianinas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/metabolismo , Animais , Antocianinas/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/etiologia , Suplementos Nutricionais , Humanos
4.
Crit Rev Food Sci Nutr ; 58(17): 2867-2881, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28662339

RESUMO

Grain sorghum is an important staple food crop grown globally while sweet sorghum is increasingly considered as a promising biofuel feedstock. Biofuels are the major economic products from the processing of large quantities of biomass, which is currently being utilized to make value-added products in the biorefinery approach. To date, these value-added products are typically commodity chemicals and waste materials used in agriculture. However, there are opportunities to generate high-value bioactive compounds from sorghum grain and biomass. Chronic diseases, such as cancers, are the top causes for morbidity and mortality in developed nations and are promoted by inflammation and oxidative stress. Globally, colorectal cancer results in approximately one-half million deaths annually. It is estimated that as much as 80% of colorectal cancer cases can be attributed to environmental and dietary factors. The sorghum grain and ligno-cellulosic biomass generated for biofuel production has been reported to be high in bioactive compounds, including phenolic acids and flavonoids, with antioxidant and anti-inflammatory properties. This review focuses on the bioactive compounds of grain and sweet sorghum (Sorghum bicolor L. Moench), for their anti-inflammatory, antioxidant, anti-colon cancer, and immune modulator functions. The review summarizes previous efforts to identify and quantify bioactive compounds in sorghum and documents their anti-cancer biological activities. Finally, this review discusses bioactive compound extraction methodologies and technologies as well as considerations for incorporating these technologies into current biorefining practices.


Assuntos
Grão Comestível/química , Compostos Fitoquímicos/farmacologia , Sorghum/fisiologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/química
5.
BMC Complement Altern Med ; 16: 278, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27506388

RESUMO

BACKGROUND: We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known. METHODS: We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo. RESULTS: RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear ß-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed - proliferation, sphere formation, nuclear translocation of ß-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/ß-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE. CONCLUSION: The suppression of Wnt/ß-catenin signaling and elevated mitochondrial-mediated apoptosis in colon CSCs support potential clinical testing/application of grape bioactives for colon cancer prevention and/or therapy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/metabolismo , Extrato de Sementes de Uva/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Vitis/química , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Extrato de Sementes de Uva/química , Masculino , Camundongos , Células-Tronco Neoplásicas/metabolismo , Resveratrol , Transdução de Sinais/efeitos dos fármacos , Estilbenos/química , Estilbenos/farmacologia , beta Catenina/metabolismo
6.
Gastroenterology ; 146(6): 1470-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24631493

RESUMO

Recent advances that allow us to collect more data on DNA sequences and metabolites have increased our understanding of connections between the intestinal microbiota and metabolites at a whole-systems level. We can also now better study the effects of specific microbes on specific metabolites. Here, we review how the microbiota determines levels of specific metabolites, how the metabolite profile develops in infants, and prospects for assessing a person's physiological state based on their microbes and/or metabolites. Although data acquisition technologies have improved, the computational challenges in integrating data from multiple levels remain formidable; developments in this area will significantly improve our ability to interpret current and future data sets.


Assuntos
Bactérias/metabolismo , Intestinos/microbiologia , Metaboloma , Metabolômica , Microbiota , Fatores Etários , Envelhecimento/metabolismo , Animais , Bactérias/classificação , Humanos , Lactente , Recém-Nascido , Mucosa Intestinal/metabolismo , Metabolômica/métodos , Biologia de Sistemas
7.
Plant Environ Interact ; 5(1): e10128, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38323132

RESUMO

The use of arbuscular mycorrhizal fungi (AMF) as biofertilizers has proven successful in boosting the yield and nutritional quality of a variety of crops. AMF associate with plant roots and exchange soil nutrients for photosynthetically derived C in the form of sugars and lipids. Past research has shown that not all AMF species are equal in their benefit to nutrient uptake and crop health, and that the most beneficial AMF species appear to vary by host species. Although an important human food staple, especially in developing regions where nutrient deficiency is a prevalent threat to public health, little work has been done to test the effectiveness of AMF in enhancing the nutritional quality of common bean (Phaseolus vulgaris L.). Therefore, our objective was to determine the most beneficial AMF species for inoculation of this important crop. We inoculated black beans (Phaseolus vulgaris black turtle beans) with eight individual AMF species and one mixed species inoculum in an outdoor pot trial over 3 months and assessed the extent to which they altered yield, mineral nutrient and anthocyanin concentration of seeds and leaf tissues. Despite seeing no yield effects from inoculation, we found that across treatments percent root length colonized by AMF was positively correlated with plant tissue P, Cu, and Zn concentration. Underlying these broad benefits, seeds from plants inoculated with three AMF species, Claroideoglomus claroideum (+15%), Funneliformis mosseae (+13%), and Gigaspora rosea (+11%) had higher P concentration than non-mycorrhizal plants. C. claroideum also increased seed potassium (K) and copper (Cu), as well as leaf aluminum (Al) concentration making it a promising candidate to further test the benefit of individual AMF species on black bean growth in field trials.

8.
Nutrients ; 16(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38613113

RESUMO

The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The variability in responses to soy has been partly attributed to differences in the metabolism of soy isoflavones, compounds with structural similarities to estrogen. Approximately one-third of humans possess gut bacteria capable of converting soy isoflavone daidzein into equol, a metabolite produced exclusively by gut microbiota with significant estrogenic potency. In contrast, lab-raised rodents are efficient equol producers, except for those raised germ-free. This discrepancy raises concerns about the applicability of traditional rodent models to humans. Herein, we designed a gnotobiotic mouse model to differentiate between equol producers and non-producers by introducing synthetic bacterial communities with and without the equol-producing capacity into female and male germ-free mice. These gnotobiotic mice display equol-producing phenotypes consistent with the capacity of the gut microbiota received. Our findings confirm the model's efficacy in mimicking human equol production capacity, offering a promising tool for future studies to explore the relationship between endogenous equol production and health outcomes like cardiometabolic health and fertility. This approach aims to refine dietary guidelines by considering individual microbiome differences.


Assuntos
Equol , Isoflavonas , Humanos , Feminino , Masculino , Animais , Camundongos , Modelos Animais de Doenças , Cetonas , Fenótipo
9.
Foods ; 12(9)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37174384

RESUMO

Isolated anthocyanins have limited colonic bioavailability due to their instability as free forms. Thus, many methods have been fabricated to increase the stability of anthocyanins. Complexation, encapsulation, and co-pigmentation with other pigments, proteins, metal ions, and carbohydrates have been reported to improve the stability and bioavailability of anthocyanins. In this study, anthocyanins extracted from purple potatoes were complexed with four different polysaccharides and their mixture. The anthocyanin-polysaccharide complexes were characterized using a zeta potential analyzer, particle size analyzer, scanning electron microscopy, and Fourier-transform infrared spectroscopy. Complexes were subjected to simulated digestion for assessing the stability of anthocyanins. Furthermore, complexes were subjected to different pH conditions and incubated at high temperatures to monitor color changes. A Caco-2 cell monolayer was used to evaluate the colonic concentrations of anthocyanins. In addition, the bioactivity of complexes was assessed using LPS-treated Caco-2 cell monolayer. Results show that pectin had the best complexation capacity with anthocyanins. The surface morphology of the anthocyanin-pectin complex (APC) was changed after complexation. APC was more resistant to the simulated upper gastrointestinal digestion, and high pH and temperature conditions for a longer duration. Furthermore, APC restored the lipopolysaccharide (LPS)-induced high cell permeability compared to isolated anthocyanins. In conclusion, complexation with pectin increased the stability and colonic bioavailability and the activity of anthocyanins.

10.
Gut Microbes ; 15(1): 2221095, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305942

RESUMO

Impacts of dietary fiber on intestinal inflammation are complex, but some specific semi-purified fibers, particularly psyllium, can protect humans and rodents against colitis. Mechanisms underlying such protection are not fully understood but may involve activation of the FXR bile acid receptor. Obesity and its associated consequences, referred to as metabolic syndrome, are associated with, and promoted by, low-grade inflammation in a variety of tissues including the intestine. Hence, we examined whether psyllium might ameliorate the low-grade intestinal inflammation that occurs in diet-induced obesity and, moreover, the extent to which it might ameliorate adiposity and/or dysglycemia in this disease model. We observed that enriching a high-fat diet with psyllium provided strong protection against the low-grade gut inflammation and metabolic consequences that were otherwise induced by the obesogenic diet. Such protection was fully maintained in FXR-deficient mice, indicating that distinct mechanisms mediate psyllium's protection against colitis and metabolic syndrome. Nor did psyllium's protection associate with, or require, fermentation or IL-22 production, both of which are key mediators of beneficial impacts of some other dietary fibers. Psyllium's beneficial impacts were not evident in germfree mice but were observed in Altered Schaedler Flora mice, in which psyllium modestly altered relative and absolute abundance of the small number of taxa present in these gnotobiotic mice. Thus, psyllium protects mice against diet-induced obesity/metabolic syndrome by a mechanism independent of FXR and fermentation but nonetheless requires the presence of at least a minimal microbiota.


Assuntos
Colite , Microbioma Gastrointestinal , Síndrome Metabólica , Psyllium , Humanos , Animais , Camundongos , Síndrome Metabólica/prevenção & controle , Dieta Ocidental , Obesidade/prevenção & controle , Fibras na Dieta , Inflamação
11.
Food Funct ; 14(21): 9606-9616, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37814601

RESUMO

The rising incidence of inflammatory bowel disease (IBD) has necessitated the search for safe and effective novel therapeutic strategies. Dietary flavonoids exhibited antioxidant, antiproliferative, and anticarcinogenic activities in several model systems with proven abilities to reduce inflammation and oxidative stress, thus they could be promising therapeutic agents for IBD prevention/treatment. However, understanding the role of a specific class of compounds in foods that promote health is difficult because of the chemically complex food matrices. This study aimed to utilize four maize near-isogenic lines to determine the anti-colitis effects of specific classes of flavonoids, anthocyanins and/or phlobaphenes, in a whole-food matrix. Results showed that the intake of anthocyanin and phlobaphene-enriched maize diets effectively alleviated dextran sodium sulfate (DSS)-induced colitis in mice via reducing the intestinal permeability and restoring the barrier function. Anthocyanin diets were more effective in maintaining the crypt structure and muc2 protein levels and reducing inflammation. Bacterial communities of mice consuming diets enriched with anthocyanins and phlobaphenes were more similar to the healthy control compared to the DSS control group, suggesting the role of flavonoids in modulating the gut microbiota to retrieve intestinal homeostasis. Microbiota depletion rendered these compounds ineffective against colitis. Lower serum concentrations of several phenolic acids were detected in the microbiota-depleted mice, indicating that gut microbiota plays a role in flavonoid metabolism and bioavailability.


Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Camundongos , Antocianinas/farmacologia , Zea mays , Dextranos , Promoção da Saúde , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Flavonoides/efeitos adversos , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismo
12.
Cell Mol Gastroenterol Hepatol ; 15(6): 1421-1442, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36828279

RESUMO

BACKGROUND & AIMS: Fiber-rich foods promote health, but mechanisms by which they do so remain poorly defined. Screening fiber types, in mice, revealed psyllium had unique ability to ameliorate 2 chronic inflammatory states, namely, metabolic syndrome and colitis. We sought to determine the mechanism of action of the latter. METHODS: Mice were fed grain-based chow, which is naturally rich in fiber or compositionally defined diets enriched with semi-purified fibers. Mice were studied basally and in models of chemical-induced and T-cell transfer colitis. RESULTS: Relative to all diets tested, mice consuming psyllium-enriched compositionally defined diets were markedly protected against both dextran sulfate sodium- and T-cell transfer-induced colitis, as revealed by clinical-type, histopathologic, morphologic, and immunologic parameters. Such protection associated with stark basal changes in the gut microbiome but was independent of fermentation and, moreover, maintained in mice harboring a minimal microbiota (ie, Altered Schaedler Flora). Transcriptomic analysis revealed psyllium induced expression of genes mediating bile acids (BA) secretion, suggesting that psyllium's known ability to bind BA might contribute to its ability to prevent colitis. As expected, psyllium resulted in elevated level of fecal BA, reflecting their removal from enterohepatic circulation but, in stark contrast to the BA sequestrant cholestyramine, increased serum BA levels. Moreover, the use of BA mimetics that activate the farnesoid X receptor (FXR), as well as the use of FXR-knockout mice, suggested that activation of FXR plays a central role in psyllium's protection against colitis. CONCLUSIONS: Psyllium protects against colitis via altering BA metabolism resulting in activation of FXR, which suppresses pro-inflammatory signaling.


Assuntos
Colite , Psyllium , Camundongos , Animais , Psyllium/efeitos adversos , Ácidos e Sais Biliares , Promoção da Saúde , Colite/induzido quimicamente , Colite/prevenção & controle , Colite/metabolismo , Inflamação , Camundongos Knockout
13.
Plant Foods Hum Nutr ; 67(2): 111-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22477645

RESUMO

Obesity is closely associated with increased incidence of cardiovascular diseases, cancer, insulin resistance, and immune dysfunction, and thus obesity-mitigation strategies should take into account these secondary pathologies in addition to promoting weight loss. Recent studies indicate that black cumin (Nigella sativa) has cardio-protective, anti-cancer, anti-diabetic, antioxidant, and immune-modulatory properties. While black cumin and/or its major bioactive constituent, thymoquinone have demonstrated bioactivity in a variety of disease models, the mechanisms of action are largely unknown. Given the growing interest in and the use of functional foods and nutraceuticals, as well as the increase in obesity and chronic diseases worldwide, further research into the therapeutic/preventive effects of black cumin may be beneficial.


Assuntos
Benzoquinonas/farmacologia , Nigella sativa/química , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/prevenção & controle , Quimiorradioterapia Adjuvante/métodos , Humanos , Resistência à Insulina , Neoplasias/complicações , Neoplasias/prevenção & controle , Nigella sativa/toxicidade , Obesidade/complicações , Redução de Peso
14.
Nutrients ; 14(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35745145

RESUMO

During oxidative stress, degenerative diseases such as atherosclerosis, Alzheimer's, and certain cancers are likely to develop. Recent research on canary seed (Phalaris canariensis) peptides has demonstrated the high in vitro antioxidant potential. Thus, this study aimed to assess the cellular and in vivo antioxidant capacity of a low-molecular-weight (<3 kDa) canary seed peptide fraction (CSPF) using Caco-2 cells and the Caenorhabditis elegans model. The results show that the CSPF had no cytotoxicity effect on Caco-2 cells at any tested concentration (0.3−2.5 mg/mL). Additionally, the cellular antioxidant activity (CAA) of the CSPF was concentration-dependent, and the highest activity achieved was 80% by the CSPF at 2.5 mg/mL. Similarly, incubation with the CSPF significantly mitigated the acute and chronic oxidative damage, extending the lifespan of the nematodes by 88 and 61%, respectively. Furthermore, it was demonstrated that the CSPF reduced the accumulation of reactive oxygen species (ROS) to safe levels after sub-lethal doses of pro-oxidant paraquat. Quantitative real-time PCR revealed that the CSPF increased the expression of oxidative-stress-response-related gene GST-4. Overall, these results show that the CSPFs relied on GST-4 upregulation and scavenging of free radicals to confer oxidative stress protection and suggest that a CSPF can be used as a natural antioxidant in foods for health applications.


Assuntos
Caenorhabditis elegans , Phalaris , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Células CACO-2 , Humanos , Longevidade , Estresse Oxidativo , Peptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sementes/metabolismo
15.
Biomed Pharmacother ; 146: 112486, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34891113

RESUMO

BACKGROUND AND AIMS: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10-/-] mouse model. METHODS: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. RESULTS: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. CONCLUSIONS: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.


Assuntos
Ampicilina/efeitos adversos , Antibacterianos/efeitos adversos , Colite/induzido quimicamente , Interleucina-10/genética , Neomicina/efeitos adversos , Animais , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Feminino , Hipersensibilidade Alimentar , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Knockout , Mucina-2/metabolismo , Permeabilidade
16.
Proteome Sci ; 9(1): 49, 2011 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-21849056

RESUMO

BACKGROUND: We and others have previously reported that resveratrol (RSV) suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or in vivo, however molecular mechanisms are not fully elucidated. Particularly, little information is available on RSV's effects on metabolic pathways and the cell-extra cellular matrix (ECM) communication that are critical for cancer cell growth. To identify important targets of RSV, we analyzed whole protein fractions from HT-29 advanced human colon cancer cell line treated with solvent control, IGF-1 (10 nM) and RSV (150 µM) using LC/MS/MS-Mud PIT (Multidimensional Protein Identification Technology). RESULTS: Pentose phosphate pathway (PPP), a vital metabolic pathway for cell cycle progression, was elevated and suppressed by IGF-1 and RSV, respectively in the HT-29 cell line. Enzymatic assays confirmed RSV suppression of glucose-6 phosphate dehydrogenase (rate limiting) and transketolase, key enzymes of the PPP. RSV (150 µM) suppressed, whereas IGF-1 (10 nM) elevated focal adhesion complex (FAC) proteins, talin and pFAK, critical for the cell-ECM communication. Western blotting analyses confirmed the suppression or elevation of these proteins in HT-29 cancer cells treated with RSV or IGF-1, respectively. CONCLUSIONS: Proteomic analysis enabled us to establish PPP and the talin-pFAK as targets of RSV which suppress cancer cell proliferation and induce apoptosis in the colon cancer cell line HT-29. RSV (150 µM) suppressed these pathways in the presence and absence of IGF-1, suggesting its role as a chemo-preventive agent even in obese condition.

17.
Foods ; 10(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34681345

RESUMO

With entomophagy gaining popularity in the Western hemisphere as a solution for future food insecurity, research on alternative protein sources, such as edible insects, has become relevant. Most of the research performed on insects has been on their nutritional qualities; however, little is known regarding bioactive compounds, such as polyphenols, that, if present in the insect, could provide additional benefits when the insect is consumed. In this study, methanolic extracts of Acheta domesticus from two farms and their corresponding feeds were obtained using a microwave-assisted extraction. Targeted phenolic characterization was accomplished through LC-MS/MS leading to the identification of 4-hydroxybenzoic acid, p-coumaric acid, ferulic acid, and syringic acid as major phenolic compounds in both A. domesticus extracts. Furthermore, the in vitro antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical cation (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical assays demonstrating the superior quenching activity of the A. domesticus extracts compared to the feeds. The discovery of phenolic compounds in A. domesticus implies the ability of this insect species to sequester and absorb dietary phenolics leading to possible added health benefits when consumed.

18.
Mol Nutr Food Res ; 65(24): e2100152, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34633750

RESUMO

SCOPE: Anthocyanin-containing potatoes exert anti-inflammatory activity in colitic mice. Gut bacterial dysbiosis plays a critical role in ulcerative colitis. This study examined the extent to which the anti-colitic activity of anthocyanin-containing red/purple-fleshed potatoes depends on the gut bacteria using a chemically-induced rodent model of colitis with the intact and antibiotic-ablated microbiome. METHODS AND RESULTS: Four-week-old male mice (C57BL6) are randomly assigned to the control diet or 20% purple-/red-fleshed potatoes supplemented diet group. The microbiota-ablated group received an antibiotic cocktail in drinking water. At week nine, colitis is induced by 2% dextran sulfate sodium (DSS) in drinking water for five days. Administration of antibiotics resulted in a 95% reduction in gut bacterial load and fecal SCFAs. DSS-induced elevated gut permeability and body weight loss are more pronounced in antibiotic mice compared to non-antibiotic mice. Purple- or red-fleshed potato supplementation (20% w/w) ameliorated DSS-induced reduction in colon length and mucin 2 expression levels, and increase in permeability, spleen weight, myeloperoxidase (MPO) activity, and inflammatory cytokines (IL-6, IL-17, and IL1-ß) expression levels in non-antibiotic mice, but not in gut microbiota ablated mice. CONCLUSIONS: Anthocyanin-containing potatoes are potent in alleviating colitis, and the gut microbiome is critical for the anti-colitic activity of anthocyanin-containing potatoes.


Assuntos
Colite , Microbioma Gastrointestinal , Solanum tuberosum , Animais , Antocianinas/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
19.
J Nutr Biochem ; 93: 108616, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33705951

RESUMO

Ulcerative colitis (UC), a major form of inflammatory bowel disease (IBD), is on the rise worldwide. Approximately three million people suffer from IBD in the United States alone, but the current therapeutic options (e.g., corticosteroids) come with adverse side effects including reduced ability to fight infections. Thus, there is a critical need for developing effective, safe and evidence-based food products with anti-inflammatory activity. This study evaluated the antiinflammatory potential of purple-fleshed potato using a dextran sodium sulfate (DSS) murine model of colitis. Mice were randomly assigned to control (AIN-93G diet), P15 (15% purple-fleshed potato diet) and P25 (25% purple-fleshed potato diet) groups. Colitis was induced by 2% DSS administration in drinking water for six days. The results indicated that purple-fleshed potato supplementation suppressed the DSS-induced reduction in body weight and colon length as well as the increase in spleen and liver weights. P15 and P25 diets suppressed the elevation in the intestinal permeability, colonic MPO activity, mRNA expression and protein levels of pro-inflammatory interleukins IL-6 and IL-17, the relative abundance of specific pathogenic bacteria such as Enterobacteriaceae, Escherichia coli (E. coli) and pks+ E. coli, and the increased flagellin levels induced by DSS treatment. P25 alone suppressed the elevated systemic MPO levels in DSS-exposed mice, and elevated the relative abundance of Akkermansia muciniphila (A. muciniphila) as well as attenuated colonic mRNA expression level of IL-17 and the protein levels of IL-6 and IL-1ß. Therefore, the purple-fleshed potato has the potential to aid in the amelioration of UC symptoms.


Assuntos
Antocianinas/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Solanum tuberosum/química , Ração Animal , Animais , Antocianinas/química , Bactérias/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Solanum tuberosum/metabolismo
20.
Cell Mol Gastroenterol Hepatol ; 12(3): 983-1000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33940221

RESUMO

BACKGROUND & AIMS: Nourishment of gut microbiota via consumption of fermentable fiber promotes gut health and guards against metabolic syndrome. In contrast, how dietary fiber impacts type 1 diabetes is less clear. METHODS: To examine impact of dietary fibers on development of type 1 diabetes in the streptozotocin (STZ)-induced and spontaneous non-obese diabetes (NOD) models, mice were fed grain-based chow (GBC) or compositionally defined diets enriched with a fermentable fiber (inulin) or an insoluble fiber (cellulose). Spontaneous (NOD mice) or STZ-induced (wild-type mice) diabetes was monitored. RESULTS: Relative to GBC, low-fiber diets exacerbated STZ-induced diabetes, whereas diets enriched with inulin, but not cellulose, strongly protected against or treated it. Inulin's restoration of glycemic control prevented loss of adipose depots, while reducing food and water consumption. Inulin normalized pancreatic function and markedly enhanced insulin sensitivity. Such amelioration of diabetes was associated with alterations in gut microbiota composition and was eliminated by antibiotic administration. Pharmacologic blockade of fermentation reduced inulin's beneficial impact on glycemic control, indicating a role for short-chain fatty acids (SCFA). Furthermore, inulin's microbiota-dependent anti-diabetic effect associated with SCFA-independent restoration of interleukin 22, which was necessary and sufficient to ameliorate STZ-induced diabetes. Inulin-enriched diets significantly delayed diabetes in NOD mice. CONCLUSIONS: Fermentable fiber confers microbiota-dependent increases in SCFA and interleukin 22 that, together, may have potential to prevent and/or treat type 1 diabetes.


Assuntos
Bactérias/classificação , Diabetes Mellitus Tipo 1/tratamento farmacológico , Fibras na Dieta/administração & dosagem , Ácidos Graxos Voláteis/metabolismo , Interleucinas/metabolismo , Inulina/administração & dosagem , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/microbiologia , Fibras na Dieta/farmacologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Inulina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/fisiopatologia , Estreptozocina/efeitos adversos , Resultado do Tratamento , Interleucina 22
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