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1.
Mol Nutr Food Res ; 65(21): e2100434, 2021 Nov.
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.
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.

3.
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
4.
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
5.
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
6.
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
7.
Mol Nutr Food Res ; 63(23): e1900626, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31574574

RESUMO

SCOPE: Obesity is a chronic condition resulting in excessive fat accumulation in adipose tissues. Adipose tissue is now considered as an immune organ, at the crossroads between metabolism and immunity. Thus, this study investigates the effects of adzuki beans on obesity and gut microbiota in high fat diet-induced mice. METHODS AND RESULTS: In this study, adzuki bean hot water extract (AWE) is determined to have the most significant anti-adipogenic effect; it is able to inhibit lipid accumulation in 3T3-L1 adipocytes and reduces body weight and adipose tissue weight in a dose-dependent manner. AWE treatment also decreases M1-polarized adipose tissue macrophages (ATMs) while inducing M2-polarized ATMs. The number and size of fat vacuoles in liver lesions are significantly reduced, indicating that AWE could ameliorate steatosis in high fat diet-induced mice. The results also demonstrate that AWE-treated groups inhibit adipogenesis via activating the Wnt/ß-catenin pathway and reduce peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding proteins α expression. Moreover, the studies confirm that AWE decreases obesity through modulating gut microbiota. CONCLUSION: The results demonstrate that AWE supplementation ameliorates high fat diet-induced obesity and gut microbiota composition and suggests that AWE may have the potential to be developed into a functional food to improve metabolic disorders.


Assuntos
Fármacos Antiobesidade/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vigna , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Animais , Polaridade Celular/efeitos dos fármacos , Dieta Hiperlipídica , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Via de Sinalização Wnt/efeitos dos fármacos
8.
Mol Nutr Food Res ; 63(2): e1800390, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30516329

RESUMO

SCOPE: Obesity has become a major health problem worldwide and is associated with low-grade chronic inflammation and intestinal dysbiosis. This study is conducted to investigate the chemopreventive effects of garcinol, a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica. How garcinol protects against obesity in high-fat diet (HFD)-induced mice is delineated and whether its anti-obesity effects are related to gut microbiota has been determined. METHODS AND RESULTS: The results show that garcinol reduces HFD-fed mice body weight gain and relative visceral adipose tissue fat weight in a dose-dependent manner. Furthermore, garcinol markedly reduces the plasma levels of glutamate pyruvate transaminase, total cholesterol, and triacylglycerol. The 16S rRNA gene sequence data indicate that garcinol not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios-but also controls inflammation by increasing the intestinal commensal bacteria, Akkermansia. In addition, the AMP-activated protein kinase α signaling pathway involved in adipocyte adipogenesis is also affected by garcinol. CONCLUSION: Taken together, these results demonstrate for the first time that garcinol can prevent HFD-induced obesity and may be used as a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/prevenção & controle , Terpenos/farmacologia , Adenilato Quinase/fisiologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/patologia , Animais , Dieta Hiperlipídica , Disbiose/induzido quimicamente , Endocanabinoides/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
10.
J Agric Food Chem ; 66(4): 773-779, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29295622

RESUMO

Current views support the concept that obesity is linked to a worsening of the course of inflammatory bowel diseases (IBDs). Gut microbiota and adipose tissue macrophage (ATM) are considered key mediators or contributors in obesity-associated intestinal inflammation. Dietary components can have direct or indirect effects on "normal" or "healthy" microbial composition and participate in adiposity and metabolic status with gut inflammation. In this perspective, we highlight food-derived bioactives that have a potential application in the prevention of obesity-exacerbated IBD, targeting energy metabolism, M1 (classical activated)-M2 (alternatively activated) macrophage polarization, and gut microbiota.


Assuntos
Dieta , Doenças Inflamatórias Intestinais/prevenção & controle , Obesidade/complicações , Compostos Fitoquímicos/administração & dosagem , Tecido Adiposo/fisiopatologia , Adiposidade/fisiologia , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Obesidade/microbiologia , Obesidade/fisiopatologia
11.
Biofactors ; 44(1): 26-35, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29220106

RESUMO

Epigenetic mechanisms are essential in regulating normal cellular functions and play an important role during the disease developmental stages. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cancer, neurological disorders, bone and skeletal diseases, cardiovascular dysfunction, and metabolic syndrome. The molecular mechanisms of epigenetic modification include DNA methylation, histone modification (acetylation, methylation and phosphorylation), and microRNAs (miRNAs). Unlike genetic modifications, epigenetic states of genes are reversible and can be altered by certain intrinsic and extrinsic factors. In the past few decades, accumulated evidence shows that dietary phytochemicals with chemopreventive effects are also potent epigenetic regulators. Resveratrol and pterostilbene are stilbenoids, which have been reported to have anti-cancer, anti-inflammatory, anti-lipid, and anti-diabetic properties. Stilbenoids are also reported to improve cardiovascular disease. By altering DNA methylation and histone modification or by modulating miRNA expression, resveratrol, and pterostilbene become potent epigenetic modifiers. In this review, we summarize these studies and underlying mechanisms of resveratrol and pterostilbene and their influence on epigenetic mechanisms. © 2017 BioFactors, 44(1):26-35, 2018.


Assuntos
Anti-Inflamatórios/farmacologia , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Epigênese Genética/efeitos dos fármacos , Estilbenos/farmacologia , Doenças Ósseas/genética , Doenças Ósseas/metabolismo , Doenças Ósseas/patologia , Doenças Ósseas/prevenção & controle , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , Quimioprevenção , Metilação de DNA/efeitos dos fármacos , Histonas/genética , Histonas/metabolismo , Humanos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/prevenção & controle , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/prevenção & controle , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Resveratrol
12.
J Agric Food Chem ; 65(44): 9655-9664, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29032686

RESUMO

3'-Hydroxypterostilbene (trans-3,5-dimethoxy-3',4'-hydroxystilbene) presents in Sphaerophysa salsula, Pterocarpus marsupium, and honey bee propolis and has been reported to exhibit several biological activities. Herein, we aimed to explore the chemopreventive effects of dietary 3'-hydroxypterostilbene and underlying molecular mechanisms on colitis-associated cancer using the azoxymethane (AOM)/dextran sodium sulfate (DSS) model. 3'-Hydroxypterostilbene administration effectively ameliorated the colon shortening and number of tumors in AOM/DSS-treated mice (3.2 ± 1.2 of the high-dose treatment versus 13.8 ± 5.3 of the AOM/DSS group, p < 0.05). Molecular analysis exhibited the anti-inflammatory activity of 3'-hydroxypterostilbene by a significant decrease in the levels of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6 (IL-6) (p < 0.05). Moreover, dietary 3'-hydroxypterostilbene also significantly diminished IL-6/signal transducer and activator of transcription signaling and restored colonic suppressor of cytokine signaling 3 levels in the colonic tissue of mice (p < 0.05). Collectively, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary 3'-hydroxypterostilbene against colitis-associated colonic tumorigenesis.


Assuntos
Anticarcinógenos/administração & dosagem , Carcinogênese/efeitos dos fármacos , Colite/complicações , Neoplasias do Colo/prevenção & controle , Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Estilbenos/administração & dosagem , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Colite/genética , Colite/metabolismo , Neoplasias do Colo/etiologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Humanos , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos
13.
J Med Food ; 19(9): 830-5, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27542074

RESUMO

We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55-60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15-20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo/metabolismo , Fármacos Antiobesidade/farmacologia , Citrus/química , Flavonas/farmacologia , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Células 3T3-L1 , Acetil-CoA Carboxilase , Monofosfato de Adenosina/metabolismo , Adipócitos , Animais , Fármacos Antiobesidade/uso terapêutico , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Flavonas/uso terapêutico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Frutas/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Obesidade/tratamento farmacológico , PPAR gama/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas Quinases/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo
14.
J Med Food ; 19(7): 663-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27200471

RESUMO

Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1ß) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging. The natural vitamin K2-menaquinone-7 (MK-7) added to the cell culture of human monocyte-derived macrophages (hMDMs) at the same time as toll-like receptor (TLR) agonists did not influence the production of TNF-α. When the cells were pretreated up to 6 h with MK-7 before treatment with TLR agonists, MK-7 did not inhibit significantly the production of TNF-α after the TLR activation. However, 30 h pretreatment of hMDMs with at least 10 µM of MK-7 effectively and dose dependently inhibited the proinflammatory function of hMDMs. Pretreatment of hMDMs with 10 µM of MK-7 for 30 h resulted in 20% inhibition of TNF-α production after lipopolysaccharide (LPS) activation (P < .05) and 43% inhibition after macrophage-activating lipopeptide (MALP) activation (P < .001). Pathogen-associated molecular pattern (PMPP) activation was inhibited by 20% with MK-7 pretreatment; however, this inhibition was not statistically significant. The 30 h pretreatment of a THP-1-differentiated monocyte cell line with MK-7 resulted in a dose-dependent downregulation of TNFα, IL-1α, and IL-1ß gene expression as evaluated by RNA semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MK-7 is able to modulate immune and inflammatory reactions in the dose-response inhibition of TNF-α, IL-1α, and IL-1ß gene expression and protein production by the healthy hMDMs in vitro.


Assuntos
Interleucina-1alfa/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Macrófagos/efeitos dos fármacos , Receptores Toll-Like/agonistas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vitamina K 2/análogos & derivados , Anti-Inflamatórios , Linhagem Celular , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1alfa/genética , Interleucina-1beta/genética , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/genética , Vitamina K 2/farmacologia
15.
J Agric Food Chem ; 64(4): 821-30, 2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26777574

RESUMO

Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Adipogenesis is a key process that is required in adipocyte hypertrophy in the development of obesity. Curcumin (Cur) has been reported to inhibit adipocyte differentiation, but the inhibitory effects of other curcuminoids present in turmeric, such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), on adipogenesis have not been investigated. Here, we investigated the effects of curcuminoids on adipogenesis and the molecular mechanisms of adipocyte differentiation. Among three curcuminoids, BDMC was the most effective suppressor of lipid accumulation in adipocytes. BDMC suppressed adipogenesis in the early stage primarily through attenuation of mitotic clonal expansion (MCE). In BDMC-treated preadipocytes, cell cycle arrest at the G0/G1 phase was found after initiation of adipogenesis and was accompanied by downregulation of cyclin A, cyclin B, p21, and mitogen-activated protein kinase (MAPK) signaling. The protein levels of the adipogenic transcription factors peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding proteins (C/EBP)α were also reduced by BDMC treatment. Furthermore, 0.5% dietary BDMC (w/w) significantly lowered body weight gain and adipose tissue mass in high-fat diet (HFD)-fed mice. The results of H&E staining showed that dietary BDMC reduced hypertrophy in adipocytes. These results demonstrate for the first time that BDMC suppressed adipogenesis in 3T3-L1 adipocytes and prevented HFD-induced obesity. Our results suggest that BDMC has the potential to prevent obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Curcumina/análogos & derivados , Obesidade/tratamento farmacológico , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Diarileptanoides , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo
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