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1.
Mol Nutr Food Res ; : e1900550, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675164

RESUMO

Neurological disorders occur in the central and peripheral nervous system and include Alzheimer's disease, stroke, and spinal cord injury. Activation of the innate immune system inevitably occurs in all forms of neurological disorders. The NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome is a multimolecular complex that can sense danger signals associated with neurological disorders. Assembly of the NLRP3 inflammasome promotes caspase-1-mediated interleukin-1ß and interleukin-18 maturation in microglia, where neuroinflammation contributes to neurological disease development and progression. Thus, this review attempts to elucidate the current knowledge regarding NLRP3 inflammasome activation and its crucial role in the pathogenesis of neurological disorders. Recent scientific findings with respect to neuroprotective effects of dietary phytochemicals against NLRP3 inflammasome-mediated neurological disorders summarized in this review suggest that modulation of the NLRP3 inflammasome assembly by plant-derived phytochemicals could be a potential strategy for prevention or treatment of neurological disorders.

2.
J Agric Food Chem ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31735033

RESUMO

Obesity is a global public health issue. Thermogenesis is a novel way to promote anti-obesity by consuming energy as heat rather than storing it as triacylglycerols. The browning program allows mitochondrial biosynthesis and thermogenesis-related gene expression to occur in subcutaneous white adipose tissue, which results in formation of beige adipose tissue. Some phytochemicals have exerted the capability to activate fat browning processing. Resveratrol and oxyresveratrol are both natural stilbenoids that have been reported for their anti-obesity efficacy. However, the comparison between the two as they relate to thermogenesis as well as the differences in their underlying mechanisms are still not widely discussed. Our result reveals that both resveratrol and oxyresveratrol could elevate the expression of thermogenesis-related protein expression including UCP1 (Uncoupling protein-1) and PRDM (PR domain containing 16) via Sirt1/PGC-1α (Sirtuin 1/Peroxisome proliferation gamma coactivator-1 α) activation. However, it is suggested that the transcriptional factor PPARα (Peroxisome proliferator-activator receptor α) was activated by resveratrol (1.38 ± 0.07 fold) but not oxyresveratrol. Conversely, C/EBPß (CCAAT/Enhancer-binding protein ß) was upregulated by oxyresveratrol (1.58 ± 0.05 fold) but not by resveratrol. On the other hand, CPT1 (Carnitine palmitoyltransferase) was found to be significantly activated at lower concentrations of oxyresveratrol up to 1.89 ± 0.04 fold as compared to HFD, and it could be a leading reason for UCP1 activation. Lastly, adiponectin expression was promoted in all experimental groups (1.53 ± 0.08 and 1.49 ± 0.11 fold in RES and HOXY, respectively), which could be an activator for mitochondrial biosynthesis and UCP1 expression.

3.
J Food Biochem ; : e13088, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646682

RESUMO

The seeds of tree peony (Paeonia ostii) are promulgated as emerging edible oil crops. However, biological properties of principal constituents of peony seeds were not well studied. Fifteen main constituents including suffruticosols A and B, trans-ε-viniferin, ampelopsin E, resveratrol, trans-resveratrol-4'-O-ß-d-glucopyranoside, paeoniflorin, luteolin, luteolin-4'-O-ß-d-glucopyranoside, apigenin, kaempferol, oleanic acid, betulinic acid, hederagenin, and caffeic acid were isolated and identified. Their cytotoxicity against human tumor cell lines (COLO205, HT-29, HepG2, AGS, and HL-60) were evaluated. Among them, trans-ε-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 µM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 µM) and HT-29 (IC50 4.2 µM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 µM) and AGS (IC50 5.4 µM) cells. Three enzymes (tyronsinase, α-glucosidase, and acetylcholinesterase) inhibitory activities of 12 compounds were also screened. Stilbene compounds, especially suffruticosols A and B, showed a significant inhibitory activity on all three enzymes. PRACTICAL APPLICATIONS: The cytotoxicity of 15 main constituents from peony seeds against COLO205, HT-29, HepG2, AGS, and HL-60 cells were evaluated. Among them, trans-ε-viniferin showed the most potent cytotoxicity against HL-60 cells (IC50 5.6 µM); ampelopsin E exhibited the most obvious antiproliferative properties on COLO205 (IC50 78.1 µM) and HT-29 (IC50 4.2 µM) cells, and betulinic acid showed the strongest growth inhibitory effects on HepG2 (IC50 6.6 µM) and AGS (IC50 5.4 µM) cells. Collectively, these results suggested that Paeonia ostii seed (POS) extracts are potential candidates for anticancer agents.

4.
Mol Nutr Food Res ; : e1900626, 2019 Oct 01.
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.

5.
J Agric Food Chem ; 67(40): 11119-11128, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31525874

RESUMO

Xanthohumol (Xan) is a prenylated chalcone mainly found in hops; it has been demonstrated to function against hypercholesterolemia, hyperlipidemia, and atherosclerosis. In this study, we focused on the hypocholesterolemic effect of Xan on cholesterol uptake and the underlying molecular mechanisms of Xan in human intestinal Caco-2 cells. The microarray data showed that Niemann-Pick C1-like 1 (NPC1L1), an essential transporter for dietary cholesterol absorption, was significantly downregulated in Xan-treated Caco-2 cells. We demonstrated that Xan (10 and 20 µM) suppressed the mRNA and protein expression of NPC1L1 by 0.65 ± 0.12-fold and 0.54 ± 0.15-fold and 0.72 ± 0.04-fold and 0.44 ± 0.12-fold, respectively, compared to that of the vehicle-treated Caco-2 cells. Moreover, Xan (10 and 20 µM) significantly inhibited cholesterol uptake by approximately 12 and 32% in Caco-2 cells. NPC1L1 promoter activity was significantly suppressed by Xan, and a DNA element within the NPC1L1 promoter involved in Xan-mediated NPC1L1 reduction located between the -120 and -20 positions was identified. Moreover, Xan markedly decreased the mRNA and protein levels of hepatocyte nuclear factor 4α (HNF-4α), a critical activator of NPC1L1 transcription, and subsequently attenuated HNF-4α/NPC1L1 promoter complex formation, resulting in the suppression of NPC1L1 gene expression. Finally, we demonstrated that Xan markedly abolished lovastatin-induced NPC1L1 overexpression in Caco-2 cells. These findings reveal that Xan suppresses NPC1L1 expression via downregulation of HNF-4α and exerts inhibitory effects on cholesterol uptake in the intestinal Caco-2 cells. Our findings suggest Xan could serve as a potential cholesterol-lowering agent and supplement for statin therapy.


Assuntos
Colesterol/metabolismo , Flavonoides/farmacologia , Fator 4 Nuclear de Hepatócito/metabolismo , Proteínas de Membrana/genética , Propiofenonas/farmacologia , Anticolesterolemiantes/farmacologia , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/genética , Humanos , Proteínas de Membrana/metabolismo , Regiões Promotoras Genéticas
6.
J Agric Food Chem ; 67(37): 10321-10329, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31419115

RESUMO

Pterostilbene (PTS) is a phenolic compound with diverse pharmacologic activities. However, its potential for inhibiting obesity-related colorectal cancer (CRC) remains unclear. Our study evaluated the mechanism of inhibitory effects of PTS on adipocyte conditioned-medium (aCM)-induced malignant transformation in HT-29 colorectal adenocarcinoma cells. The results demonstrated that PTS could downregulate the expression of aCM-induced fatty acid-binding protein 5 (FABP5) and prometastatic factors such as vascular endothelial growth factor, matrix metalloproteinase-2 (MMP2), MMP9, and extracellular tumor necrosis factor α via inhibiting aCM-induced nuclear factor-kappa B (NF-κB), ß-catenin, and peroxisome proliferator-activated receptor γ (PPAR-γ). Moreover, PTS can suppress aCM-stimulated phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinases 1/2 (JNK 1/2) signaling pathways activation that are upstream of NF-κB, ß-catenin, and PPAR-γ. Therefore, we suggest that PTS could alleviate adiposity-induced metastasis in CRC via inhibiting cell migration through downregulating FABP5 gene expression.


Assuntos
Adipócitos/metabolismo , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/fisiopatologia , Meios de Cultivo Condicionados/química , Proteínas de Ligação a Ácido Graxo/metabolismo , Estilbenos/farmacologia , Células 3T3 , Animais , Linhagem Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Meios de Cultivo Condicionados/metabolismo , Regulação para Baixo/efeitos dos fármacos , Proteínas de Ligação a Ácido Graxo/genética , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Mol Nutr Food Res ; 63(20): e1900514, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368236

RESUMO

SCOPE: A gut-microbiota-dependent metabolite of L-carnitine, trimethylamine-N-oxide (TMAO), has been recently discovered as an independent and dose-dependent risk factor for cardiovascular disease (CVD). This study aims to investigate the effects of pterostilbene on reducing TMAO formation and on decreasing vascular inflammation in carnitine-feeding mice. METHODS AND RESULTS: C57BL/6 mice are treated with 1.3% carnitine in drinking water with or without pterostilbene supplementation. Using LC-MS/MS, the result shows that mice treated with 1.3% carnitine only significantly increased the plasma TMAO and pterostilbene supplementation group can reverse it. Additionally, pterostilbene decreases hepatic flavin monooxygenase 3 (FMO3) mRNA levels compared to carnitine only group. It appears that pterostilbene can alter host physiology and create an intestinal microenvironment favorable for certain gut microbiota. Gut microbiota analysis reveals that pterostilbene increases the abundance of Bacteroides. Further, pterostilbene decreases mRNA levels of vascular inflammatory markers tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin). CONCLUSION: These data suggest that amelioration of carnitine-induced vascular inflammation after consumption of pterostilbene is partially mediated via modulation of gut microbiota composition and hepatic enzyme FMO3 gene expression.

8.
J Agric Food Chem ; 67(28): 7869-7879, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31287296

RESUMO

Carnitine, a dietary quaternary amine mainly from red meat, is metabolized to trimethylamine (TMA) by gut microbiota and subsequently oxidized to trimethylamine-N-oxide (TMAO) by host hepatic enzymes, flavin monooxygenases (FMOs). The objective of this study aims to investigate the effects of flavonoids from oolong tea and citrus peels on reducing TMAO formation and protecting vascular inflammation in carnitine-feeding mice. The results showed that mice treated with 1.3% carnitine in drinking water significantly (p < 0.05) increased the plasma levels of TMAO compared to control group, whereas the plasma TMAO was remarkedly reduced by flavonoids used. Meanwhile, these dietary phenolic compounds significantly (p < 0.05) decreased hepatic FMO3 mRNA levels compared to carnitine only group. Additionally, oolong tea extract decreased mRNA levels of vascular inflammatory markers such as tissue necrosis factor-alpha (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Polymethoxyflavones significantly lowered the expression of VCAM-1 and showed a decreasing trend in TNF-α and E-selectin mRNA expression compared to the carnitine group. Genus-level analysis of the gut microbiota in the cecum showed that these dietary phenolic compounds induced an increase in the relative abundances of Bacteroides. Oolong tea extract-treated group up-regulated Lactobacillus genus, compared to the carnitine only group. Administration of polymethoxyflavones increased Akkermansia in mice.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Camellia sinensis/química , Carnitina/metabolismo , Citrus/química , Flavonas/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Aterosclerose/genética , Aterosclerose/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biotransformação/efeitos dos fármacos , Feminino , Flavonas/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Metilaminas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
J Agric Food Chem ; 67(22): 6169-6176, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31117553

RESUMO

Dietary choline and its containing foods are biotransformed to trimethylamine (TMA) via gut microbial metabolism. Subsequently, as an intermediate molecule, TMA is quickly transported and oxidized in the liver by hepatic flavin monooxygenases to form trimethylamine oxide (TMAO). TMAO was treated as a waste byproduct from choline metabolism, but recent convincing evidence demonstrated the association between the small molecule TMAO and inflammation-related diseases, including blood vessel inflammation and vascular diseases. The scope of this study is to investigate the preventive effect of nobiletin on TMAO-induced blood vessel inflammation. Our results from Western blot showed that the inhibition of TMAO-induced cardiovascular inflammation was correlated with nobiletin-mediated inhibitory effects on NF-κB and MAPK/ERK related pathways. More specifically, nobiletin prevented the oxidative damage of vascular sites (proximal aorta), inhibited the activity of MAPK/ERK, reduced the expression of NF-κB p65 and phospho-NF-κB p65, and consequently decreased the inflammatory response. Flow cytometry analyses showed that nobiletin decreased TMAO-induced apoptosis of HUVEC cells and counteracted TMAO-induced HUVEC cell proliferation. Results from HE staining and immunohistochemical results also showed that nobiletin reduced the degree of inflammation of the proximal aorta in Sprague-Dawley rats. In summary, nobiletin significantly reduced TMAO-induced vascular inflammation via inhibition of the NF-κB/MAPK pathways.


Assuntos
Flavonas/administração & dosagem , Quinases de Proteína Quinase Ativadas por Mitógeno/imunologia , Fator de Transcrição RelA/imunologia , Doenças Vasculares/prevenção & controle , Animais , Aorta/efeitos dos fármacos , Aorta/imunologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Metilaminas/efeitos adversos , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/genética , Doenças Vasculares/induzido quimicamente , Doenças Vasculares/genética , Doenças Vasculares/imunologia
10.
Phytomedicine ; 57: 377-384, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30831486

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common hereditary neurocutaneous disorders. The malignant peripheral nerve sheath tumor (MPNST), transformed from NF1 related plexiform neurofibroma, is a rapidly growing and highly invasive tumor. No effective chemotherapeutic agent is currently available. Calebin-A is a derivative from turmeric Curcuma longa. Given the anti-inflammatory and anticancer potentials of curcumin, whether Calebin-A also had the tumoricidal effect upon MPNST cells is still elusive. PURPOSE: To determine whether Calebin-A has the potential for anti-MPNST effect. METHODS: The MTT and FACS analysis of normal Schwann (HSC) and MPNST cells have been employed to determine the tumoricidal effect of Calebin-A. The expression of the signal pathway molecules was assessed by Western blotting. The CHIP with quantitative PCR assay was performed to quantify the promoter DNA binding to acetylated histone 3 (acetyl H3). The enzyme activities of histone acetyltransferase (HAT) and deacetylase (HDAC) have been evaluated by commercial kits. The measurements of tumor size of the xenograft mouse model were also performed. RESULTS: Calebin-A inhibited the proliferation of MPNST and primary neurofibroma cells in a dose-dependent manner. The flow cytometry analysis of the MPNST cells after treatment of 25 µm of Calebin-A demonstrated an increase of population in the G0/G1 phase but decrease in G2/M phase. Before treatment, the expression of Axl, Tyro3, and acetyl H3 was significantly higher in MPNST cells when compared to HSC. The expression of phosphorylated-AKT, -ERK1/2, survivin, hTERT, and acetyl H3 proteins were reduced after treatment. The CHIP assay shows the promoter DNA copies of survivin (BRIC5) and hTERT genes are significantly reduced post-treatment. The enzyme activity of HAT was significantly reduced, but not that of HDAC. Two HAT inhibitors, epigallocatechin-3-gallate (EGCG) and anacardic acid (AA) have also demonstrated a significant inhibitory effect on MPNST cells. Finally, the measurements of tumor size showed a significant reduction of the xenograft tumors after treatment of Calebin-A. CONCLUSION: Both in vitro and in vivo studies showed Calebin-A could inhibit the proliferation of MPNST with suppression of survivin and hTERT. The reduced expression of these two factors might be through the epigenetic histone modification resulting from the decreased activity of HAT.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cinamatos/farmacologia , Histona Acetiltransferases/metabolismo , Monoterpenos/farmacologia , Neoplasias da Bainha Neural/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Neoplasias da Bainha Neural/enzimologia , Neoplasias da Bainha Neural/patologia , Neurofibroma Plexiforme/patologia , Neurofibromatose 1/patologia , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Survivina/genética , Survivina/metabolismo , Telomerase/genética , Telomerase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Food Funct ; 10(3): 1767, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30778488

RESUMO

Correction for 'From white to beige adipocytes: therapeutic potential of dietary molecules against obesity and their molecular mechanisms' by Siyu Wang et al., Food Funct., 2019, DOI: 10.1039/c8fo02154f.

12.
Toxins (Basel) ; 11(2)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717134

RESUMO

Aflatoxins are highly toxic and cause disease in livestock and humans. In order to assess Taiwan population exposure to aflatoxin from peanuts and peanut products, a total of 1089 samples of peanut candy, peanut butter, and peanuts etc. were collected in the period from 2011 to 2017 and analyzed using a liquid chromatography/tandem mass spectrometer. The overall mean contamination levels of aflatoxin in peanuts and peanut products were 2.40 µg/kg of aflatoxin B1, 0.41 µg/kg of aflatoxin B2, 0.19 µg/kg of aflatoxin G1, and 0.03 µg/kg of aflatoxin G2. We use margin of exposure (MOE) as a tool to improve food safety management. According to MOE levels of aflatoxins in peanuts and peanut products from China, Indonesia, Thailand, the United States, and the Philippines were above the safe lower limit of 10,000, indicating an absence of public health or safety risk for the majority of the population. However, products from Vietnam were under the MOE safe lower limit, suggesting that regulatory actions must be continued to avoid excessive consumer exposure.

13.
Food Funct ; 10(3): 1263-1279, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30735224

RESUMO

The global incidence of obesity and its complications continue to rise along with a demand for novel therapeutic approaches. In addition to classic brown adipose tissue (BAT), the formation of brown-like adipocytes called beige adipocytes, within white adipose tissue (WAT), has attracted much attention as a therapeutic target due to its inducible features when stimulated, resulting in the dissipation of extra energy as heat. There are various dietary agents that are able to modulate the beige-development process by interacting with critical molecular signaling cascades, leading to the enhancement of thermogenesis. Although challenges still remain regarding the origin of the beige adipocytes, the crosstalk with activation of BAT and induction of the beiging of white fat may provide attractive potential strategies for management of obesity.


Assuntos
Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/fisiologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/fisiologia , Obesidade/prevenção & controle , Animais , Dieta , Metabolismo Energético , Humanos
14.
J Agric Food Chem ; 67(6): 1666-1673, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30629413

RESUMO

The extraction of phenolics from jujube peel (PJP) was optimized using response surface methodology (RSM). A Box-Behnken design was utilized to analyze the effects of NaOH concentration, temperature, and extraction time on the total phenolic content (TPC). The results showed that RSM could be an adequate approach for modeling the extraction of PJP. The optimal extraction condition for the highest TPC was obtained with 3.4 M NaOH concentration for 67 min at 50 °C. Not only PJP but also phenolics from the jujube seed (PJS) contain considerable amounts of phenolics, particularly flavonoids. Quercetin and galangin were found to be the predominant phenolics. PJP markedly down-regulated the levels iNOS and COX-2 proteins in macrophages by inhibiting the activation of NF-κB through interfering with the MAPK signaling pathways. Compared to PJS, PJP presented higher anti-inflammatory activities, reflecting increased amounts of TPC and total flavonoid content (TFC). These findings suggest that PJP could be a potential source of anti-inflammatory agents.


Assuntos
Anti-Inflamatórios/farmacologia , Macrófagos/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Ziziphus/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Ciclo-Oxigenase 2/imunologia , Frutas/química , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
15.
J Food Drug Anal ; 27(1): 184-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30648571

RESUMO

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-ß/Smad signaling in a dose-dependent manner compared with CCl4 treatment alone. CCM111 markedly inhibited TGF-ß, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl4-induced liver fibrosis by the cooperative inhibition of TGF-ß-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.

16.
Mol Nutr Food Res ; : e1800390, 2018 Dec 05.
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 was conducted to investigate the chemopreventive effects of garcinol, a polyisoprenylated benzophenone derivative isolated from the fruit rind of Garcinia indica. We sought to delineate how garcinol protects against obesity in high-fat diet (HFD)-induced mice and determine whether its anti-obesity effects are related to gut microbiota. METHODS AND RESULTS: The results showed that garcinol reduced HFD-fed mice body weight gain and relative visceral adipose tissue fat weight in a dose-dependent manner. Furthermore, garcinol markedly reduced the plasma levels of glutamate pyruvate transaminase, total cholesterol, and triacylglycerol. The 16S rRNA gene sequence data indicated that garcinol not only reversed HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios-but also controlled inflammation by increasing the intestinal commensal bacteria, Akkermansia. In addition, the AMP-activated protein kinase α signaling pathway involved in adipocyte adipogenesis was 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 moderator to prevent HFD-induced gut dysbiosis and obesity-related metabolic disorders. This article is protected by copyright. All rights reserved.

17.
Food Funct ; 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30411763

RESUMO

Freshwater clams (Corbicula fluminea) have long been used as a folk remedy in Chinese tradition. Their hot-water extract has been commercialized as a functional drink for liver protection. The objective of this study was to develop a product of the residual clam meat (FCR) and assess its functional compounds. The ethanol extract of FCR, designated FCRE, was identified to comprise phytosterols, polyunsaturated fatty acids (PUFAs) and carotenoids. FCRE significantly reduced lipid accumulation and cell death in HepG2 cells via decreased fatty acid synthase (FAS) activity and increased activities of carnitine palmitoyltransferase (CPT) and acyl-CoA oxidase (ACO), indicative of suppressed lipogenesis and increased ß-oxidation of fatty acids. In tilapia fed with high-fat diet (HFD), FCRE mitigated nonalcoholic steatohepatitis (NASH), which was evidenced by decreased levels of plasma aspartate transaminase (AST) and alanine transaminase (ALT), in addition to reduced total cholesterol and accumulation of triacylglycerols, particularly those of saturated and monounsaturated fatty acids. FCRE also suppressed stearoyl-CoA desaturase-1 (SCD-1) index, increased the PUFAs' n3/n6 ratio, and reduced prostaglandin E2 (PGE2) and inflammatory infiltrates in tilapia liver. Tilapia fed with HFD for 2 weeks displayed NASH symptoms, while mice took 10 weeks to display NASH symptoms. No previous study has been reported on the potential use of tilapia as an NASH model for pre-screening hepatoprotective-functional foods.

18.
J Agric Food Chem ; 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30415544

RESUMO

Diet-induced obesity is strongly associated with nonalcoholic fatty-liver disease (NAFLD) and insulin resistance. We aimed to investigate the in vivo therapeutic value of tetrahydrocurcumin (THC) intervention in high-fat-diet (HFD)-induced obesity and hepatic steatosis. C57BL/6 mice were fed an HFD for 10 weeks, and then they received 20 or 100 mg/kg THC along with the HFD for another 10 weeks. Mice fed an HFD for 20 weeks experienced obesity, hepatic steatosis, hyperlipidemia, and insulin resistance. Tetrahydrocurcumin (THC) intervention for 10 weeks significantly reduced adiposity (epididymal-fat weights of 6.6 ± 0.4 g for the HFD-only group and 5.3 ± 0.8 and 5.6 ± 0.7 g for the HFD with 20 mg/kg THC and HFD with 100 mg/kg THC groups, respectively; p < 0.05) via downregulation of adipogenic factors. Inflammatory macrophage infiltration and polarization were decreased by THC in mouse epididymal adipose tissues. In the liver, THC markedly alleviated steatosis by approximately 28-37% ( p < 0.05) via the downregulation of lipogenesis, the activation of AMP-activated protein kinase (AMPK), and the increase of fatty acid oxidation. Elevated blood glucose and insulin resistance were also improved by THC, which might be caused by regulation of the hepatic insulin signaling cascade, gene transcription involved in glucose metabolism, and reduced macrophage infiltration in the liver and adipose tissue. Our results demonstrated the beneficial effects of THC-mediated intervention against obesity and NAFLD as well as other metabolic syndromes, revealing a novel therapeutic use of THC in obese populations.

20.
Mol Nutr Food Res ; 62(23): e1800392, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30168668

RESUMO

Starting from the 21st century, breast cancer can be classified as the most common invasive malignancy in women. Among the preventive or therapeutic strategies of breast cancer, combination therapy is the most promising approach. This mode of treatment of breast cancer concurrently maximizes efficacy, overcomes multidrug resistance, and minimizes harmful side effects caused by radiotherapy and chemotherapy alone. The risk of cancer can be reduced by supplementing diets with naturally occurring products known as phytochemicals. These phytochemicals have well-defined roles in the management of every stage of breast carcinogenesis. In this review, the collective data of dietary phytochemicals used to sensitize breast cancer cells to therapeutic approaches are reported and their specific molecular targets through synergistic, additive, and potentiation effects are highlighted. The concept of combining natural agents with medicines to augment therapeutic responses creates an optimal modality, which may facilitate clinical applications of combination regimens in the future.

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