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1.
Mol Nutr Food Res ; : e2100434, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506670

RESUMO

SCOPE: A causal relationship between circadian misalignment and microbiota dysbiosis has been discussed recently, due to their association to pathogenesis. Herein, the possible impact of pterostilbene (PSB) and resveratrol (RES) on the gut microbiota brought by chronic jet-lag in mice is investigated. METHODS AND RESULTS: Dietary supplement of RES and PSB (0.25%) are given to 16 week-jetlagged mice to examine the effects on microbiota and physiological functions. Jetlag significantly induces weight gained that could be effectively prevented by PSB. Both supplements also retain oscillation patterns that found to be lost in jetlag induced (JLG) group, including serum biochemical parameters and gut microbiota. The results of beta diversity suggest the supplementations efficiently lead to distinct gut microbial composition as compared to JLG group. Besides, the supplementation forestalls some microbial elevation, such as Eubacterium ventriosum and Acetitomaculum. Growth of health beneficial bacteria like Blautia and Lachnospiraceae UCG-001 is facilitated and abundance of these bacteria could be correlated to oscillation of biochemical parameters. Result of KEGG indicates distinct effect brought by microbial re-shaping. CONCLUSION: The result suggests that supplementation of RES and PSB could potentially dampen some adverse effects of gut microbiota dysbiosis, and at the same time, re-composite and facilitate the growth of health beneficial microbiota.

2.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443472

RESUMO

Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart has been previously; and in this study, its anticancer efficacy is investigated. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and the upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rose to 36.9 and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anticancer effect, and FER showed a greater proapoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Curcumina/farmacologia , Mitocôndrias/efeitos dos fármacos , Estirenos/farmacologia , Antineoplásicos/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Curcumina/química , Curcumina/metabolismo , Ciclina B1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/agonistas , Fase G2/efeitos dos fármacos , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Fenol/química , Fenol/farmacologia , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Estirenos/química , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/agonistas
3.
J Agric Food Chem ; 69(35): 10036-10057, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460268

RESUMO

Biological targeting or molecular targeting is the main strategy in drug development and disease prevention. However, the problem of "off-targets" cannot be neglected. Naturally derived drugs are preferred over synthetic compounds in pharmaceutical markets, and the main goals are high effectiveness, lower cost, and fewer side effects. Single-target drug binding may be the major cause of failure, as the pathogenesis of diseases is predominantly multifactorial. Naturally derived drugs are advantageous because they are expected to have multitarget effects, but not off-targets, in disease prevention or therapeutic actions. The capability of phytochemicals to modulate molecular signals in numerous diseases has been widely discussed. Among them, stilbenoids, especially resveratrol, have been well-studied, along with their potential molecular targets, including AMPK, Sirt1, NF-κB, PKC, Nrf2, and PPARs. The analogues of resveratrol, pterostilbene, and hydroxylated-pterostilbene may have similar, if not more, potential biological targeting effects compared with their original counterpart. Furthermore, new targets that have been discussed in recent studies are reviewed in this paper.


Assuntos
Estilbenos , Resveratrol
4.
Food Funct ; 12(17): 7805-7815, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231603

RESUMO

Liver fibrosis is a progression of chronic liver disease characterized by excess deposition of fibrillary collagen. The aim of this study was to investigate the protective effect of a triterpenoid-enriched extract (TEE) from bitter melon leaves against carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. Male ICR mice received TEE (100 or 150 mg kg-1) by daily oral gavage for one week before starting CCl4 administration and throughout the entire experimental period. After intraperitoneal injection of CCl4 for nine weeks, serum and liver tissues of the mice were collected for biochemical, histopathological and molecular analyses. Our results showed that TEE supplementation reduced CCl4-induced serum aspartate aminotransferase and alanine aminotransferase activities. Histopathological examinations revealed that CCl4 administration results in hepatic fibrosis, while TEE supplementation significantly suppressed hepatic necroinflammation and collagen deposition. In addition, TEE supplementation decreased α-smooth muscle actin (α-SMA)-positive staining and protein levels of α-SMA and transforming growth factor-ß1. TEE-supplemented mice had lower mRNA expression levels of interleukin-6, tumor necrosis factor-α, and toll-like receptor 4. Moreover, TEE (150 mg kg-1) supplementation significantly reduced intrahepatic inflammatory Ly6C+ monocyte infiltration. We demonstrated that TEE could ameliorate hepatic fibrosis by regulating inflammatory cytokine secretion and α-SMA expression in the liver to reduce collagen accumulation.

5.
Mol Nutr Food Res ; 65(17): e2100410, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34245224

RESUMO

SCOPE: Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer can be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. This study investigates the potential role of garcinol supplementation in ameliorating obesity-induced colon cancer development. METHODS AND RESULTS: An animal model to investigate the effect of high-fat-diet (HFD)-induced obesity on promoting colitis-associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)-induced) is designed. The results show that HFD can promote colitis-associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet can significantly ameliorate obesity-promoted colon carcinogenesis. The results also reveals that the microbiota composition of each group is significantly different and clustered. The most representative genera are Alistipes, Romboutsia, and Ruminococcus. The RNA-sequencing results show that the administration of garcinol can regulate genes and improve obesity-promoting colitis-associated colon carcinogenesis. CONCLUSION: The study results suggest that garcinol can prevent obesity-promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents.

6.
Food Chem Toxicol ; 155: 112380, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216713

RESUMO

The intake of common polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), is strongly correlated to the initiation of colon cancer. BaP is a well-known pro-carcinogen that is metabolically activated by xenobiotic-metabolizing enzymes. Studies indicate that polymethoxyflavones, including 5-demethylnobiletin (5-DMNB), exhibit anti-inflammatory and anti-carcinogenic properties. However, the effects of 5-DMNB on xenobiotic-metabolizing enzymes and BaP-induced carcinogenesis remain unclear. The combination of BaP and a promoting agent-dextran sulfate sodium (DSS)-has been demonstrated to induce tumors in mouse models. Thus, this study aimed to determine the protective effect of 5-DMNB on carcinogen biotransformation and BaP/DSS-induced colon carcinogenesis. Our results showed that 5-DMNB had a substantial inhibitory effect on CYP1B1 induced by BaP and upregulated the detoxification enzymes UDP-glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs). Furthermore, subsequent analyses confirmed that the dietary administration of 5-DMNB markedly ameliorated tumor formation in BaP/DSS-treated mice. Exposure to BaP/DSS also significantly elevated TNF-α levels, and the administration of 5-DMNB reversed this increase. Taken together, we determined that 5-DMNB attenuates BaP/DSS-induced colon cancer through the regulation of inflammation and xenobiotic-metabolizing enzymes. These results indicate that 5-DMNB has significant potential as a novel chemopreventive agent for preventing carcinogen activation and inflammation-associated carcinogenesis.

7.
J Agric Food Chem ; 69(25): 7093-7103, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34152136

RESUMO

The worldwide prevalence of obesity has significantly increased over the past few decades. It is currently believed that obesity is a risk factor for developing inflammatory bowel disease. Pterostilbene (PTS), a naturally occurring stilbene from blueberries, is known to have anticancer, anti-inflammation, antifibrosis, and antiobesity effects. The preventive effect of PTS on the susceptibility of high-fat diet (HFD) to dextran sulfate sodium (DSS)-induced colitis in mice was investigated. Beginning at 5 weeks of age, C57BL/6J mice were fed a normal diet, 50% HFD alone, or containing PTS, and DSS (2.5%, w/v) was given in drinking water at week 9 and week 11. The results demonstrated that PTS significantly attenuated HFD and DSS-induced plasma interleukin-6 accumulation. Moreover, PTS suppressed HFD/DSS-induced formation of aberrant crypt foci and reduced the colon weight-to-length ratio in HFD/DSS-induced colitis mice. Furthermore, PTS inhibited interleukin-1ß (IL-1ß), the C/EBP homologous protein (CHOP), cyclooxygenase-2, and transforming growth factor beta-1 (TGF-ß1)/mothers against decapentaplegic homolog 2 expression and maintained mucin2 (Muc2) and E-cadherin expressions. In addition, post-treatment with PTS also decreased the colon weight-to-length ratio and loss of Muc2. Moreover, the CHOP, IL-1ß, matrix metalloproteinase-2, and TGF-ß1 expressions were significantly decreased in HFD/DSS-induced colitis mice after post-treatment with PTS. In conclusion, the results of the present study suggest that PTS is of significant interest for the prevention of HFD/DSS-induced colitis in C57BL/6J mice.


Assuntos
Colite , Estilbenos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo/patologia , Sulfato de Dextrana , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fibrose , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Metaloproteinase 2 da Matriz , Camundongos , Camundongos Endogâmicos C57BL
8.
J Agric Food Chem ; 69(16): 4745-4754, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33848157

RESUMO

The overweight and obese population has skyrocketed, resulting in a high incidence of metabolic disorders. Agardhiella subulata (AS) contains a variety of beneficial components, such as sulfur-containing polysaccharides (dietary fiber) and astaxanthin, which is considered to have anti-obesity potential. In this study, we investigated the effects and possible mechanisms of dietary AS on high-fat diet (HFD)-induced obesity in mice. AS supplementation significantly reduced HFD-induced weight gain (19%) and the visceral adiposity index (4.1%). In addition, the level of total cholesterol, triglyceride, and low-density lipoprotein was significantly decreased; adiponectin was significantly increased in serum and fecal triglyceride excretion was significantly higher in mice fed AS compared with mice on an HFD. Preadipocyte factor 1 and Sry-box transcription factor 9 that were significantly higher than the levels found for the HFD group lead to reduced adipogenesis. Moreover, accompanying the lipolysis and fatty acid ß-oxidation that occur in the AS group, the concentration of non-esterified fatty acids was lowered to 0.4 ± 0.1 mEq/L. In addition, peroxisome proliferator-activated receptor γ and phosphorylation acetyl-CoA carboxylase increased 1.5- and 1-fold, thus increasing the expression of adiponectin and the activation of AMPK and ultimately resulting in lower blood glucose levels. The results of this study suggest that AS supplementation increases lipid excretion and improves energy metabolism to prevent obesity in mice fed a HFD.


Assuntos
Fármacos Antiobesidade , Dieta Hiperlipídica , Adipogenia , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica/efeitos adversos , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética
9.
J Food Sci ; 86(6): 2491-2498, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33929043

RESUMO

The interaction mechanism between liposomes (Lips) and whey protein isolates (WPI) with different mass ratios was explored in this paper. After binding with different concentration of Lips, the changes in hydrophilic and hydrophobic regions of WPI were investigated with fluorescein isothiocyanate (FITC) and pyrene fluorescence probes. The spatial structure changes of WPI were further characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and circular dichroism. The results indicated that the structure of WPI was changed due to binding with Lips in hydrophilic and hydrophobic groups. The binding process might result in the migration, recombination, and alignment of WPI and Lip groups. Moreover, the oil-water interfacial tension with WPI decreased from 9.20 mN/m to 3.29 mN/m upon increasing the Lip-to-WPI ratio. This work suggests that the physiochemical properties of Lip-WPI complexes could be manipulated by adjusting the Lip-to-WPI ratio. This study shed some light on the mechanism explanation of the WPI structural changes due to the interaction with Lips during food processing.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Lipossomos/metabolismo , Proteínas do Soro do Leite/metabolismo , Varredura Diferencial de Calorimetria , Lipossomos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tensão Superficial , Proteínas do Soro do Leite/química
10.
Food Res Int ; 142: 110143, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33773654

RESUMO

Obesity is related to energy imbalance and energy metabolism. In this study, we investigated the anti-obesity effects of Garcinia indica extract (GIE), Coleus forskohlii extract (CFE), and the combinations of these two extracts in a 3T3-L1 cells and high-fat diet (HFD)-induced obese mice. In vitro, GIE showed better effect on TG content than CFE, CFE showed better effect on glycerol released than GIE, and the combinations of GIE and CFE showed both effects compared with GIE and CFE alone. In vivo, GIE, LMIX (0.005% GIE + 0.025% CFE), and HMIX (0.01% GIE + 0.025% CFE) down-regulated adipogenesis-related transcription factors PPARγ and C/EBPα protein expression, CFE promoted lipolysis by up-regulated p-HSL and p-PKA protein expression, and four supplementations promoted fatty acid ß-oxidation by up-regulating CPT-1A and PPARα protein expression to decrease lipid accumulation in adipose tissue. Moreover, we found that CFE, LMIX and HMIX, except GIE exert increasing the abundance of Bacteroides caccae compared with HFD group. Overall, GIE, CFE, and the combinations of GIE and CFE were able to decrease body weight and adipocyte size by promoting fatty acid ß-oxidation and modulating gut microbiota in HFD-induced obese mice.


Assuntos
Garcinia , Microbioma Gastrointestinal , Plectranthus , Animais , Bacteroides , Metabolismo Energético , Lipídeos , Camundongos , Camundongos Obesos , Extratos Vegetais/farmacologia
11.
Environ Sci Pollut Res Int ; 28(22): 28381-28390, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33543437

RESUMO

Cadmium (Cd) is a toxic pollutant that is widely spread through industrial production and agricultural practices. Epidemiological data has revealed that lifetime exposure to environmentally relevant levels of Cd increases the risk of developing various organ diseases, including chronic kidney, heart, and lung diseases, as well as nervous tissue disorders. This study assessed Cd levels in rice to determine the health risks associated with rice consumption in various age-gender subgroups in Taiwan. The distribution of Cd concentration, the lifetime average daily dose (LADD), and the hazard index (HI) were estimated by Monte Carlo simulation. In the general population, the 50th percentile LADD of Cd for male rice consumers between the ages of 19-65 years was 0.06 µg/kg body weight per day, and the hazard index (HI) 50th, 90th, and 95th percentiles were 0.16, 0.69, and 1.54, respectively. According to the HI heat map for the exposure of the general population to Cd from rice in Taiwan, the highest exposure to Cd was noted in the Yilan area (HI 0.64). Therefore, rice production in the Yilan area should be further monitored to evaluate the levels of Cd contamination.


Assuntos
Metais Pesados , Oryza , Poluentes do Solo , Adulto , Idoso , Cádmio/análise , Contaminação de Alimentos/análise , Humanos , Masculino , Metais Pesados/análise , Pessoa de Meia-Idade , Medição de Risco , Poluentes do Solo/análise , Taiwan , Adulto Jovem
12.
Phytomedicine ; 81: 153432, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310310

RESUMO

BACKGROUND: A natural pterostilbene analogue isolated from the herb Sphaerophysa salsula, 3'-hydroxypterostilbene (HPSB), exhibits antiproliferative activity in several cancer cell lines; however, the inhibitory effects of HPSB on skin carcinogenesis remains unclear. PURPOSE: The aim of this study was to evaluate the inhibitory effects of HPSB on two-stage skin carcinogenesis in mice and its potential mechanism. STUDY DESIGN AND METHODS: This study investigated the anti-inflammatory and anti-tumor effects of HPSB in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated acute skin inflammation and 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced two-stage skin carcinogenesis model. In addition, the effects of HPSB on the modulation of the phase I and phase II metabolizing enzymes in the DMBA-induced HaCaT cell model were investigated. RESULTS: The results provide evidence that topical treatment with HPSB significantly inhibits TPA-induced epidermal hyperplasia and leukocyte infiltration through the down-regulation of cyclooxygenase-2 (COX-2), matrix metalloprotein-9 (MMP-9), and ornithine decarboxylase (ODC) protein expression in mouse skin. Furthermore, HPSB suppresses DMBA/TPA-induced skin tumor incidence and multiplicity via the inhibition of proliferating cell nuclear antigen (PCNA), Cyclin B1 and cyclin-dependent kinase 1 (CDK1) expression in the two-stage skin carcinogenesis model. In addition, pretreatment with HPSB markedly reduces DMBA-induced cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) gene expression in human keratinocytes; however, HPSB does not significantly affect the gene expression of the phase II enzymes. CONCLUSION: This is the first study to show that topical treatment with HPSB prevents mouse skin tumorigenesis. Overall, our study suggests that natural HPSB may serve as a novel chemopreventive agent capable of preventing carcinogen activation and inflammation-associated tumorigenesis.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Anticarcinógenos/farmacologia , Neoplasias Cutâneas/prevenção & controle , Estilbenos/farmacologia , Acetato de Tetradecanoilforbol/toxicidade , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Anticarcinógenos/administração & dosagem , Carcinógenos/toxicidade , Ciclo-Oxigenase 2/metabolismo , Erupção por Droga/etiologia , Erupção por Droga/prevenção & controle , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Camundongos Endogâmicos ICR , Ornitina Descarboxilase/metabolismo , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Estilbenos/administração & dosagem
13.
J Agric Food Chem ; 68(49): 14513-14522, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33231468

RESUMO

Obesity is an important health issue nowadays. 3'-Hydroxydaidzein (OHD) is a metabolite of daidzein (DAI) that can be found in fermented soybean products, such as miso. DAI has been known to affect lipid accumulation, but the effect of OHD on lipid accumulation still needs to be investigated. In this study, we investigated the effects of OHD on mice with obesity induced by a high-fat diet (HFD). The results showed that mice treated with 0.1% OHD (HOHD) significantly reduced their body weight and inguinal fat without altering their food intake compared with the HFD group. The HOHD and DAI groups' hyperlipidemia were alleviated through decreased serum triacylglycerols and total cholesterol levels. The adipocyte sizes in inguinal fat were significantly smaller in the HOHD and DAI groups compared with the HFD group. Both the HOHD and DAI groups had increased PRDM16, C/EBP ß, p-p38, SIRT1, PGC1 α, and UCP1 protein expression in their inguinal adipose tissue compared with the HFD group. Moreover, the OHD and DAI groups had significantly lower amounts of Lachnospira and GCA_900066225 compared with the HFD group. Collectively, OHD can ameliorate HFD-induced obesity in mice by stimulating the browning of the white adipose tissue and modulating gut microbiota.


Assuntos
Tecido Adiposo Bege/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Isoflavonas/administração & dosagem , Obesidade/tratamento farmacológico , Tecido Adiposo Bege/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
14.
Food Funct ; 11(9): 7545-7560, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32815965

RESUMO

NAFLD (non-alcoholic fatty liver disease) is a multifactorial liver disease related to multiple causes or unhealthy conditions, including obesity and chronic inflammation. The accumulation of excess triglycerides, called steatosis, is known as a hallmark of an imbalance between the rates of hepatic fatty acid uptake/synthesis and oxidation/export. Furthermore, occurrence of NAFLD may lead to a cocktail of disease consequences caused by the altered metabolism of glucose, lipids, and lipoproteins, for instance, insulin resistance, type II diabetes, nonalcoholic steatohepatitis (NASH), liver fibrosis, and even hepatocarcinogenesis. Due to the complexity of the occurrence of NAFLD, a multi-targeting strategy is highly recommended to effectively address the issue and combat the causal loop. Ethanol extracts of legumes are popular supplements due to their richness and diversity in phytochemicals, especially isoflavones and anthocyanins. Although many of them have been reported to have efficacy in the treatment of different metabolic syndromes and obesity, there have not been many studies on them as a supplemental mixture. In this study, the alleviative effects of selected legume ethanol extracts (CrE) on high-fat-diet- and fructose-induced obesity, liver steatosis, and hyperglycemia are discussed. As revealed by the findings, CrE not only ameliorated obesity in terms of weight gained and enlargement of adipose tissue, but also significantly reduced the incidence of steatosis via phosphorylation of AMPK, resulting in inhibition of the downstream SREBP-1c/FAS pathway and an increase in an indicator of ß-oxidation (carnitine palmitoyl transferase 1a, CPT1A). Furthermore, CrE dramatically alleviated inflammatory responses, including both plasma and hepatic TNF-α, IL-6, and MCP-1 levels. CrE also had attenuating effects on hyperglycemia and insulin resistance and significantly reduced the fasting glucose level, fasting insulin level, and plasma leptin, and it exhibited positive effects in the Oral glucose tolerance test (OGTT) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). At the molecular level, CrE could activate the PI3K/Akt/Glut2 pathway, which indicated an increase in insulin sensitivity and glucose uptake. Taken together, these results suggest that ethanol extracts of legumes could be potential supplements for metabolic syndromes, and their efficacy and effectiveness might facilitate the multi-targeting strategy required to mitigate NAFLD.


Assuntos
Fabaceae/química , Frutose/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Suplementos Nutricionais/análise , Frutose/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/isolamento & purificação , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
J Agric Food Chem ; 68(35): 9345-9357, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32786868

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease due to lipid accumulation in the hepatocyte. Diet, especially a high-fat diet, is one risk factor that leads to NAFLD. Many natural compounds such as isoflavones have antiobesity effects. Therefore, intake of these functional compounds through daily dietary choices is a method of improving health. Miso is a kind of fermented soy paste, which is rich in isoflavones and has a different biological activity. In this study, we investigated the effects of different concentrations of fermented soy paste on NAFLD in high-fat-diet (HFD)-fed Sprague-Dawley (SD) rats. The results showed that 2% fermented soy paste decreased serum triacylglycerol (TG) and alanine aminotransferase (ALT) and reduced lipid accumulation in the liver through induced fatty acid oxidation by activating the adenosine 5'-monophosphate -activated protein kinase (AMPK) pathway and increasing PGC1α and CPT1α protein expression. Furthermore, we found that 2% fermented soy paste increased the abundance of Prevotellaceae NK3B31 and Desulfovibrio. Taken together, fermented soy paste improved HFD-induced lipid accumulation in the liver by activating fatty acid oxidation and modulating gut microbiota.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Alimentos de Soja/análise , Proteínas Quinases Ativadas por AMP/genética , Alanina Transaminase/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Humanos , Fígado/enzimologia , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Ratos Sprague-Dawley , Alimentos de Soja/microbiologia , Triglicerídeos/metabolismo
16.
Front Cell Dev Biol ; 8: 436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582712

RESUMO

Chronic kidney disease (CKD) is recognized as a global public health problem. NLRP3 inflammasome activation has been characterized to mediate diverse aspect mechanisms of CKD through regulation of proinflammatory cytokines, tubulointerstitial injury, glomerular diseases, renal inflammation, and fibrosis pathways. Autophagy is a characterized negative regulation mechanism in the regulation of the NLRP3 inflammasome, which is now recognized as the key regulator in the pathogenesis of inflammation and fibrosis in CKD. Thus, autophagy is undoubtedly an attractive target for developing new renal protective treatments of kidney disease via its potential effects in regulation of inflammasome. However, there is no clinical useful agent targeting the autophagy pathway for patients with renal diseases. Pterostilbene (PT, trans-3,5-dimethoxy-4-hydroxystilbene) is a natural analog of resveratrol that has various health benefits including autophagy inducing effects. Accordingly, we aim to investigate underlying mechanisms of preventive and therapeutic effects of PT by reducing NLRP3 inflammasome activation and fibrosis through autophagy-inducing effects. The renal protective effects of PT were evaluated by potassium oxonate (PO)-induced hyperuricemia and high adenine diet-induced CKD models. The autophagy induction mechanisms and anti-fibrosis effects of PT by down-regulation of NLRP3 inflammasome are investigated by using immortalized rat kidney proximal tubular epithelial NRK-52E cells. To determine the role of autophagy induction in the alleviating of NLRP3 inflammasome activation and epithelial-mesenchymal transition (EMT), NRK-52E with Atg5 knockdown [NRK-Atg5-(2)] cells were applied in the study. The results indicated that PT significantly reduces serum uric acid levels, liver xanthine oxidase activity, collagen accumulation, macrophage recruitment, and renal fibrosis in CKD models. At the molecular levels, pretreatment with PT downregulating TGF-ß-triggered NLRP3 inflammasome activation, and subsequent EMT in NRK-52E cells. After blockage of autophagy by treatment of Atg5 shRNA, PT loss of its ability to prevent NLRP3 inflammasome activation and EMT. Taken together, we suggested the renal protective effects of PT in urate nephropathy and proved that PT induces autophagy leading to restraining TGF-ß-mediated NLRP3 inflammasome activation and EMT. This study is also the first one to provide a clinical potential application of PT for a better management of CKD through its autophagy inducing effects.

17.
Biomolecules ; 10(6)2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32486019

RESUMO

In recent decades, cancer has been one of the leading causes of death worldwide. Despite advances in understanding the molecular basis of tumorigenesis, diagnosis, and clinical therapies, the discovery and development of effective drugs is an active and vital field in cancer research. Tetrahydrocurcumin is a major curcuminoid metabolite of curcumin, naturally occurring in turmeric. The interest in tetrahydrocurcumin research is increasing because it is superior to curcumin in its solubility in water, chemical stability, bioavailability, and anti-oxidative activity. Many in vitro and in vivo studies have revealed that tetrahydrocurcumin exerts anti-cancer effects through various mechanisms, including modulation of oxidative stress, xenobiotic detoxification, inflammation, proliferation, metastasis, programmed cell death, and immunity. Despite the pharmacological similarities between tetrahydrocurcumin and curcumin, the structure of tetrahydrocurcumin determines its distinct and specific molecular mechanism, thus making it a potential candidate for the prevention and treatment of cancers. However, the utility of tetrahydrocurcumin is yet to be evaluated as only limited pharmacokinetic and oral bioavailability studies have been performed. This review summarizes research on the anti-cancer properties of tetrahydrocurcumin and describes its mechanisms of action.


Assuntos
Antineoplásicos/uso terapêutico , Curcumina/análogos & derivados , Neoplasias/tratamento farmacológico , Curcumina/uso terapêutico , Humanos
18.
Am J Cancer Res ; 10(4): 1170-1181, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368393

RESUMO

Lactobacillus spp., a common probiotic used as a dietary supplement, is good for the digestive system. However, its anti-cancer activity still remains unclear. In this study, we aim to examine the effect of Lactobacillus fermentum, Lactobacillus acidophilus and Lactobacillus rhamnosus on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer. Male ICR mice were injected with 10 mg/kg AOM and 2.5% DSS via drinking water, and then fed with different Lactobacillus (1 × 108 CFU/day) for 14 weeks. The colonic tissues were collected for biomedical analysis, and gut microbiota profiling was detected by next generation high-throughput sequencing comparing to the 16S rRNA gene. We found that pretreatment with Lactobacillus fermentum (Lac.ferm) significantly inhibits colonic tumor formation (P < 0.05) and markedly decreases pro-inflammatory cytokines in AOM/DSS-induced mice. Furthermore, 16S rRNA sequencing data showed that Lac.ferm altered the composition of gut microbiota by reducing the percentage of Bacteroides. Moreover, linear discriminant analysis scores revealed that Lactobacillus fermentum within phylum Firmicutes was the prominent species existing in the Lac.ferm-treated group. Overall, the above findings suggest that dietary Lac.ferm could modulate the gut microbial community, which might be beneficial to alleviating colon cancer progression.

19.
J Sci Food Agric ; 100(13): 4776-4781, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32458424

RESUMO

BACKGROUND: In Taiwan, nearly 90% of apples and raw ingredients for apple-based products are imported. Apple juices (137 samples) and apple-containing beverages (35 samples) were collected in Taiwan from imported food and analyzed for patulin content. RESULTS: The results revealed that the incidence levels of patulin for apple juice and apple-containing beverages are 5.84% and 5.71%. The mean contamination levels were 1.7 and 1.4 µg kg-1 for apple juice and apple-containing beverages. One sample exceeded 50 µg kg-1 , the maximum permissible limit according to the Taiwan Sanitation Standard for the Tolerance of Mycotoxins in Foods. The estimated intake of patulin for consumers ranged from 5.4 to 18.0 ng kg-1 body weight per day for apple juice and between 6.1 and 11.2 ng kg-1 body weight for apple-containing beverages. The highest average patulin intake was observed among infants aged 0-3 years, followed by children aged 4-12 years old. Finally, the hazard index (HI) for the 50th, 90th, and 95th percentiles are 0.0186, 0.1201, and 0.2048, respectively, for infants aged 0-3 years. CONCLUSION: The dietary intake of patulin from imported apple juices and apple-containing beverages is well below the safety levels and does not present a risk for adult and children consumers. However, it is important to point out that we only analyzed imported apple juices and apple-containing beverages. More studies are necessary to establish if the HI for patulin will still remain below 1 when other foods and beverages are included in the risk calculations. © 2020 Society of Chemical Industry.


Assuntos
Sucos de Frutas e Vegetais/análise , Malus/química , Patulina/análise , Criança , Pré-Escolar , Qualidade de Produtos para o Consumidor , Feminino , Contaminação de Alimentos/análise , Humanos , Lactente , Masculino , Medição de Risco , Taiwan
20.
J Agric Food Chem ; 68(19): 5365-5374, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32316726

RESUMO

Epidemiological surveys show that obesity and the western diet increase the risk of colitis. Studies have also confirmed that the high-fat-diet (HFD) promoted the deterioration of colitis-related indicators in mice. Compared with stilbenoids, the results showed that 3'-hydroxypterostilbene (HPSB) was found to be the most effective inhibitor for the antiadipogenesis and anti-inflammation. However, its role in ameliorating obesity-promoted colitis is still unknown. We intend to investigate the protective effect and related molecular mechanisms of HPSB on HFD promoted dextran sodium sulfate (DSS)-induced colitis in mice. The results indicate that colitis in the HFD+DSS group tends to be more apparent in the DSS-only group, while feeding 0.025% of HPSB at different stages can improve the colitis induced by HFD+DSS. HPSB significantly reduced the levels of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) induced by HFD+DSS in mice. Furthermore, the Western blotting revealed that the administration of HPSB significantly downregulated cyclooxygenase-2 (COX-2), plasmalemma vesicle-associated protein-1 (PV-1), and phospho-signal transducer and activator of transcription 3 (p-STAT3) expressions in HFD+DSS treated mice. Presented results reveal that HPSB is a novel functional agent capable of preventing HFD exacerbated colitis.


Assuntos
Colite/tratamento farmacológico , Obesidade/complicações , Estilbenos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Sulfato de Dextrana/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Obesidade/imunologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia
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