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1.
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.

2.
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
3.
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
4.
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
5.
Am J Chin Med ; 47(8): 1833-1851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31795743

RESUMO

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citrus/química , Medicamentos de Ervas Chinesas/farmacologia , Fator 2 Relacionado a NF-E2/genética , Acetaminofen/efeitos adversos , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Flavonoides/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
6.
AAPS J ; 21(5): 86, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292765

RESUMO

Prostate cancer ranks the second in incidence and the fifth in mortality cancer in male globally. Citrus polymethoxyflavonoids (PMFs), such as tangeretin (PMF1), have been found to exhibit various biological activities. Here, we evaluated the inhibitory effects and mechanism of synthetic 5,4'-didemethyltangeretin (PMF2) on human prostate cancer LNCaP cells. We found that PMF2 inhibited the growth of LNCaP cells (GI50 14.6 µM) more strongly than PMF1, and it was less cytotoxic against the normal human prostate RWPE-1 cells. PMF2 upregulated Bad and Bax, downregulated Bcl-2, and activated caspase-3 and PARP in the LNCaP cells, thereby inducing apoptosis. PMF2 also suppressed the anchorage-independent growth of the LNCaP cells. It triggered p21 gene expression by demethylation of the p21 promoter region, and inhibited the protein expressions of DNMT 3B and HDACs 1, 2, and 4/5/9 by epigenetic regulations. We further found that PMF2 showed interactions with DNMTs 1, 2, and 3A ex vivo, which might inhibit DNMT activity. Additionally, PMF2 decreased the anchorage-independent growth of isolated LNCaP cancer stem-like cells (CSLCs) with high CD166 mRNA expression. These results indicated that PMF2 might inhibit the growth of human prostate cancer cells through different mechanisms, suggesting that PMF2 could be an innovative agent for prostate cancer therapy and prevention.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Flavonas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Epigênese Genética , Flavonas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
7.
Food Funct ; 10(3): 1767, 2019 03 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.

8.
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
9.
Food Funct ; 9(6): 3363-3373, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29855643

RESUMO

Polymethoxyflavones (PMFs) and hydroxyl PMFs (HOPMFs) are mainly found in citrus peel and have shown anti-obesity potential in in vitro and in vivo studies. Herein, we have investigated the anti-obesity effects of two citrus peel extracts obtained via supercritical fluid extraction: PMF A, with a lower content of PMFs and HOPMFs, and PMF B, with a higher content of PMFs and HOPMFs. PMF A and PMF B were administered orally for 16 weeks to mice with high fat diet (HFD)-induced obesity. The results showed that PMF B decreased the lipid content more statistically significantly (p < 0.05) than PMF A in 3T3-L1 preadipocytes, reduced the adipocyte size, decreased the adipose tissue weight and alleviated the total body weight in the HFD mice. Both PMF A and PMF B reduced the adipocyte size in the perigonadal fat by markedly decreasing the levels of lipid droplets (LD) and perilipin 1 protein and Sterol regulatory element binding protein 1 (SREBP-1) expression. Compared to the case of the HFD group, PMF B altered the gut microbiota by increasing Prevotella and decreasing rc4-4 bacteria. The change in the composition of gut microbiota, the community of symbiotic and pathogenic microorganisms, may determine the metabolic health and be responsible for the anti-obesity mechanism. Our results indicate that the citrus peel extracts decrease lipid accumulation both in vivo and in vitro and should be considered for the management of overweight and obesity conditions.


Assuntos
Bactérias/efeitos dos fármacos , Citrus/química , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Extratos Vegetais/administração & dosagem , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
J Food Drug Anal ; 25(1): 100-110, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911527

RESUMO

Dietary phytochemicals from food and herbs have been studied for their health benefits for a long time. The incidence of obesity has seen an incredible increase worldwide. Although dieting, along with increased physical activity, seems an easy method in theory to manage obesity, it is hard to apply in real life. Obesity treatment drugs and surgery are not successful or targeted for everyone and can have significant side effects. This low rate of success is the major reason that the overweight as well as the pharmaceutical industry seek alternative methods, including phytochemicals. Therefore, more and more research has focused on the role of phytochemicals to alleviate lipid accumulation or enhance energy expenditure in adipocytes. This review discusses selected phytochemicals from food and herbs and their effects on adipogenesis, lipogenesis, lipolysis, oxidation of fatty acids, and browning in 3T3-L1 preadipocytes.


Assuntos
Alimentos , Adipogenia , Animais , Humanos , Metabolismo dos Lipídeos , Obesidade , Compostos Fitoquímicos , Extratos Vegetais , Plantas Medicinais
11.
J Food Drug Anal ; 25(1): 62-70, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911544

RESUMO

Black garlic is obtained from fresh garlic (Allium sativum L.) that has been fermented for a period of time at a controlled high temperature (60-90°C) under controlled high humidity (80-90%). When compared with fresh garlic, black garlic does not release a strong offensive flavor owing to the reduced content of allicin. Enhanced bioactivity of black garlic compared with that of fresh garlic is attributed to its changes in physicochemical properties. Studies concerning the fundamental findings of black garlic, such as its production, bioactivity, and applications, have thus been conducted. Several types of black garlic products are also available in the market with a fair selling volume. In this article, we summarize the current knowledge of changes in the components, bioactivity, production, and applications of black garlic, as well as the proposed future prospects on their possible applications as a functional food product.


Assuntos
Alho , Temperatura Alta , Umidade , Extratos Vegetais
12.
Food Funct ; 8(9): 3276-3287, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28831484

RESUMO

Theasinensins have been identified as a major group of unique catechin dimers mainly found in oolong tea and black tea. Among several types of theasinensins, theasinensin A (TSA), an epigallocatechin gallate (EGCG) dimer with an R-biphenyl bond, is the most abundant theasinensin prevalent in oolong tea. Previous studies have reported that TSA exhibits antioxidative, anti-inflammatory and anti-cancer activities in vitro and in vivo. However, little is known about the hepatoprotective effect of TSA. Thus, the aim of this study was to investigate the inhibitory effect of TSA on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. After intraperitoneal injection of CCl4 for eight weeks, histological lesions in the liver tissue and elevated serum levels of alanine aminotransferase and alkaline phosphatase were found in mice. Conversely, oral administration of TSA relieved CCl4-induced liver injury as well as ameliorated liver functions. Our immunohistochemical staining results revealed that collagen deposition was profoundly reduced due to supplementation with TSA. In addition, we also found that hepatic α-smooth muscle actin (α-SMA) and matrix metallopeptidase 9 (MMP-9) expression was suppressed through the inhibition of transforming growth factor ß (TGF-ß). Taken together, our current findings suggest that TSA may serve as a potent bioactive constituent from oolong tea that acts against liver fibrosis through the inhibition of hepatic stellate cell (HSC) activation.


Assuntos
Benzopiranos/administração & dosagem , Cirrose Hepática/prevenção & controle , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Benzopiranos/química , Camellia sinensis/química , Tetracloreto de Carbono/efeitos adversos , Modelos Animais de Doenças , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Fenóis/química , Chá/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
13.
Food Funct ; 7(11): 4481-4491, 2016 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-27722362

RESUMO

Obesity is a serious health problem in adults and children worldwide. However, the basic strategies for the management of obesity (diet, exercise, drugs and surgery) have limitations and side effects. Therefore, many researchers have sought to identify bioactive components in food. Tea and coffee are the most frequently consumed beverages in the whole world. Their health benefits have been studied for decades, especially those of green tea. The anti-obesity effect of tea and coffee has been studied for at least ten years. The results have shown decreased lipid accumulation in cells via the regulation of the cell cycle during adipogenesis, changes in transcription factors and lipogenesis-related proteins in the adipose tissue of animal models, and decreased body weight and visceral fat in humans. Tea and coffee also influence the gut microbiota in obese animals and humans. Although the anti-obesity mechanism of tea and coffee still needs further clarification, they may have potential as a new strategy to prevent or treat obesity.


Assuntos
Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Café/química , Chá/química , Adipogenia/efeitos dos fármacos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos
14.
Molecules ; 21(11)2016 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-27792146

RESUMO

Obesity is a global health concern. Piceatannol (Pic), an analog of resveratrol (Res), has many reported biological activities. In this study, we investigated the anti-obesity effect of Pic in a high-fat diet (HFD)-induced obese animal model. The results showed that Pic significantly reduced mouse body weight in a dose-dependent manner without affecting food intake. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) levels, and blood glucose (GLU) were significantly lowered in Pic-treated groups. Pic significantly decreased the weight of liver, spleen, perigonadal and retroperitoneal fat compared with the HFD group. Pic significantly reduced the adipocyte cell size of perigonadal fat and decreased the weight of liver. Pic-treated mice showed higher phosphorylated adenosine 5'-monophosphate-activated protein kinase (pAMPK) and phosphorylated acetyl-CoA carboxylase (pACC) protein levels and decreased protein levels of CCAAT/enhancer-binding protein C/EBPα, peroxisome proliferator-activated receptor PPARγ and fatty acid synthase (FAS), resulting in decreased lipid accumulation in adipocytes and the liver. Pic altered the composition of the gut microbiota by increasing Firmicutes and Lactobacillus and decreasing Bacteroidetes compared with the HFD group. Collectively, these results suggest that Pic may be a candidate for obesity treatment.


Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Estilbenos/administração & dosagem , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Obesidade/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estilbenos/farmacologia
15.
J Agric Food Chem ; 64(16): 3196-205, 2016 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-27041493

RESUMO

Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs), such as nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob), are unique flavonoids that are found exclusively in citrus peels. Nobiletin has been shown to suppress adipogenesis in vitro, but the antiadipogenic activity of 5-OH-Nob has not been investigated. Both nobiletin and 5-OH-Nob have poor aqueous solubility and low oral bioavailability. We employed chemical modification to produce the acetyl derivative of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), to improve its bioavailability and bioactive efficiency. We found that 5-Ac-Nob reduced triacylglycerol (TG) content to a greater extent than 5-OH-Nob in 3T3-L1 preadipocytes. Orally administered 5-Ac-Nob resulted in a significant reduction in body weight, intra-abdominal fat, plasma and liver TG levels, and plasma cholesterol level in high fat diet-induced obese male C57BL/6J mice. The 5-Ac-Nob treatment decreased lipid accumulation by triggering the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway to alter transcriptional factors or lipogenesis-related enzymes in vivo and in vitro.


Assuntos
Adenilato Quinase/metabolismo , Dieta Hiperlipídica , Flavonas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Células 3T3-L1 , Animais , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
16.
J Agric Food Chem ; 63(20): 5008-16, 2015 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-25943382

RESUMO

Selenomethionine (SeMet) and Se-methyl-L-selenocysteine (MSeC) are natural organoselenium compounds found in garlic, onion, and broccoli. In addition, these compounds have lower toxicity and better anticancer activities than inorganic Se. This study investigated the effects of MSeC treatment on the growth of COLO 205 human colorectal adenocarcinoma cells and evaluated the mechanisms related to the MSeC-induced effects. When COLO 205 cells were treated with 200 µM MSeC for 24 h, MSeC caused 80% apoptosis in cells. MSeC increased the expression of Fas and FasL, followed by the cleavage of caspase-3, caspase-8, DNA fragmentation factor (DFF45), and poly(ADP-ribose) polymerase (PARP). MSeC also increased the levels of Bax protein and decreased the levels of Bid and Bcl-2 proteins. However, MSeC did not cause apoptosis through reactive oxygen species (ROS) stress but instead through endoplasmic reticulum (ER) stress. The cleavage of caspase-12 and caspase-9 was shown to increase the growth arrest and protein levels of DNA-damage inducible genes (GADD) 153 and 45. MSeC also downregulated the ERK1/2 and PI3K/AKT protein levels and upregulated the p38 and JNK protein levels in COLO 205 cells. These results showed that the mechanism by which MSeC induced apoptosis in COLO 205 cells involved caspase activation, the extrinsic apoptotic pathway, and the regulation of ER-stress-induced apoptosis.


Assuntos
Adenocarcinoma/fisiopatologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/fisiopatologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Selenocisteína/análogos & derivados , Adenocarcinoma/tratamento farmacológico , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Humanos , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Selenocisteína/farmacologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
17.
J Tradit Complement Med ; 2(2): 145-53, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24716127

RESUMO

Hepatoma is a leading cause of death in the world. SK-Hep-1 and HA22T/VGH cells are poorly differentiated human hepatocellular carcinoma cell lines with invasive and migratory abilities. Agaricus blazei (AB) is a mushroom with many biological effects and active ingredients, and the ethanolic extract of AB fermentation product (AB-pE) was demonstrated to inhibit the growth of hepatoma Hep3B and HepG2 cells in our previous study. In this study, we further investigated the anticancer and anti-invasive abctivities of the AB-pE. Results showed that the AB-pE inhibited the growth of SK-Hep1 and HA22T/VGH cells (with IC50 values of 26.8 and 28.7 µg/mL, respectively) and led cells toward apoptosis after 48 h of treatment. Activation of caspase-3 by AB-pE (12.5~200 µg/mL) in a dose-dependent manner was observed in both cell lines using fluorescence microscopy and flow cytometry. The apoptosis triggered by the AB-pE was regulated by the increased expression of Bax, the activation of caspase-3, caspase-9, and PARP, and the decreased expression of Bcl-2. Additionally, the AB-pE showed the potential ability to inhibit invasion of SK-Hep1 and HA22T/VGH cells according to the results of a Matrigel invasion assay. Our results suggested that the AB-pE may be a further developed for its potential against hepatoma due to its antiproliferative (via apoptosis) and anti-invasive activities in hepatoma cells.

18.
J Agric Food Chem ; 59(9): 5109-16, 2011 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-21417302

RESUMO

Currently, liver cancer is a leading cause of cancer-related death in the world. Hepatocellular carcinoma is the most common type of liver cancer. Previously, it was reported that blazeispirol A (BA) is the most active antihepatoma compound in an ethanolic extract of Agaricus blazei fermentation product. The aim of this study was to understand the antihepatoma mechanism of BA in human liver cancer Hep 3B cells. The results showed that BA inhibited the growth of Hep 3B cells and increased the percentage of cells in sub-G1 phase in a concentration- and time-dependent manner. In addition, BA treatment resulted in DNA fragmentation, caspase-9 and caspase-3 activations, poly(ADP-ribose)polymerase (PARP) degradation, down-regulation of Bcl-2 and Bcl-xL expressions, up-regulation of Bax expression, and disruption of the mitochondrial membrane potential (MMP) in Hep 3B cells. Furthermore, z-VAD-fmk, a caspase inhibitor, did not enhance the viability of BA-treated Hep 3B cells, and BA induced the release of HtrA2/Omi and apoptosis-inducing factor (AIF) from mitochondria into the cytosol. These findings suggested that BA with novel chemopreventive and chemotherapeutic potentials causes both caspase-dependent and caspase-independent cell death in Hep 3B cells.


Assuntos
Agaricus/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fatores Biológicos/farmacologia , Carcinoma Hepatocelular/enzimologia , Caspases/metabolismo , Neoplasias Hepáticas/enzimologia , Agaricus/química , Antineoplásicos/metabolismo , Fatores Biológicos/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Inibidores de Caspase , Caspases/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fermentação , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia
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