RESUMEN
Red ginseng has been widely used in health-promoting supplements in Asia and is becoming increasingly popular in Western countries. However, its therapeutic mechanisms against most diseases have not been clearly elucidated. The aim of the present study was to provide the biological mechanisms of red ginseng against various metabolic diseases. We used a systems biological approach to comprehensively identify the component-target and target-pathway networks in order to explore the mechanisms underlying the therapeutic potential of red ginseng against metabolic diseases. Of the 23 components of red ginseng with target, 5 components were linked with 37 target molecules. Systematic analysis of the constructed networks revealed that these 37 targets were mainly involved in 9 signaling pathways relating to immune cell differentiation and vascular health. These results successfully explained the mechanisms underlying the efficiency of red ginseng for metabolic diseases, such as menopausal symptoms in women, blood circulation, diabetes mellitus, and hyperlipidemia.
Asunto(s)
Suplementos Dietéticos , Panax/química , Extractos Vegetales/farmacología , Biología de Sistemas/métodos , Animales , Biomarcadores , Bases de Datos Factuales , Susceptibilidad a Enfermedades , Humanos , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Estructura Molecular , Redes Neurales de la Computación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Transducción de SeñalRESUMEN
Chronic intestinal inflammation is critical risk factor of colorectal cancer. Triticum aestivum sprouts have been reported to provide a number of health benefits and used as a dietary supplement. In this study, the authors investigated the regulatory effects of T. aestivum sprouts ethanol extract (TAEE) on experimental colorectal carcinogenesis in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model. Oral administration of TAEE significantly attenuated crypt destruction and tumor formation in AOM/DSS-treated mice. Levels of inflammatory mediators involved in colorectal carcinogenesis, that is, tumor necrosis factor-α, interkeukin (IL)-1ß, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase, were lower in the colons of 200 mg/kg TAEE-treated mice than in AOM/DSS controls (p < 0.05). Immunohistochemical staining showed that levels of nuclear factor-kappa B p65 and ß-catenin were attenuated by TAEE in the colon tissues of AOM/DSS-treated mice. Furthermore, levels of ß-catenin-related genes (cyclin D1 and c-Myc), which are known to contribute to cell cycle regulation, were decreased in the colon tissues of TAEE-treated mice versus AOM/DSS controls (p < 0.01). These results showed TAEE inhibited colon inflammation and neoplasm formation caused by AOM/DSS treatment, suggesting that TAEE could be useful for the prevention and treatment of colitis-associated colon cancer.
Asunto(s)
Neoplasias del Colon/prevención & control , Extractos Vegetales/uso terapéutico , Triticum , Animales , Azoximetano , Neoplasias del Colon/inducido químicamente , Sulfato de Dextran , Mediadores de Inflamación/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Factor de Transcripción ReIA/análisis , Triticum/química , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/análisis , beta Catenina/fisiologíaRESUMEN
Atopic dermatitis (AD) is a common chronic, recurring, inflammatory skin disease. A number of researchers have been seeking safe AD therapies for a long time. Triticum aestivum sprouts (TAEE), known as wheatgrass, are one of the most widely used health foods worldwide. They show numerous beneficial effects, including anticancer, antiinflammatory, antioxidant, antiobesity, anticolitis and antiallergy effects; however, their effect on AD is unknown. In the present study, the antiAD effects of a 70% ethanol extract of TAEE were investigated in 2,4dinitrochlorobenzene (DNCB)treated mice with ADlike skin lesions and in tumor necrosis factor (TNF)α and interferon (IFN)γstimulated human keratinocytes (HaCaT cells). Oral administration of 200 mg/kg TAEE for 10 days significantly decreased the skin thickness, transepidermal water loss and serum immunoglobulin E levels in DNCBtreated mice. In addition, TAEE reduced the secretion of inflammatory chemokines via regulation of the signal transducer and activator of transcription 1 and suppressor of cytokine signaling pathways in TNFα and IFNγstimulated HaCaT cells. These results indicate that TAEE may have beneficial effects in the treatment and prevention of AD and associated skin diseases.
Asunto(s)
Quimiocinas/genética , Dermatitis Atópica/etiología , Dermatitis Atópica/patología , Regulación de la Expresión Génica/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Extractos Vegetales/farmacología , Plantones/química , Triticum/química , Animales , Células Cultivadas , Quimiocinas/inmunología , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/efectos adversos , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Queratinocitos/inmunología , Ratones , Extractos Vegetales/química , Factor de Transcripción STAT1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
C1q is known to perform several functions in addition to the role it plays in complement activation. C1q contains a collagen-like portion and DDR1 (discoidin domain receptor 1) is a well-known collagen receptor. Accordingly, we hypothesized C1q might be a novel ligand of DDR1. This study shows for the first time C1q directly induces the activation and upregulation of DDR1, and that this leads to enhanced migration and invasion of HepG2 cells. In addition, C1q was found to induce the activations of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signaling, and to increase the expressions of matrix metalloproteinases (MMP2 and 9). Our results reveal a relationship between C1q and DDR1 and suggest C1q-induced DDR1 activation signaling may be involved in the progression of hepatocellular carcinoma.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Complemento C1q/metabolismo , Receptor con Dominio Discoidina 1/metabolismo , Neoplasias Hepáticas/metabolismo , Carcinogénesis , Carcinoma Hepatocelular/patología , Movimiento Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Regulación hacia ArribaRESUMEN
The present study was undertaken to investigate the antiobesity effect of a 50% ethanol extract of Euphorbia supina (ESEE) in highfatdiet (HFD)induced obese C57BL/6J mice. Mice were fed a HFD with or without ESEE (2, 10, or 50 mg/kg) or with Garcinia cambogia (positive control) for 6 weeks. ESEE supplementation significantly reduced body, epididymal white adipose tissue (eWAT), and organ weights (P<0.05). ESEE also reduced hepatic steatosis and improved serum lipid profiles. In addition, ESEE significantly reduced serum leptin levels and increased adiponectin levels, and significantly downregulated the mRNA and protein levels of proliferatoractivated receptor γ (PPARγ) and CCAAT/enhancerbinding protein alpha (C/EPBα) in eWAT and liver tissues (all P<0.05). These results suggested that ESEE supplementation protects against HFDinduced obesity by downregulating PPARγ and C/EPBα, and that ESEE may be beneficial for the prevention and treatment of obesity and associated diseases.
Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Euphorbia , Obesidad/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Adipogénesis/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/patología , Animales , Fármacos Antiobesidad/química , Peso Corporal/efectos de los fármacos , Euphorbia/química , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Obesidad/sangre , Obesidad/patología , Extractos Vegetales/químicaRESUMEN
Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adipogénesis/efectos de los fármacos , Chrysanthemum/química , Dieta Alta en Grasa/efectos adversos , Obesidad/metabolismo , Obesidad/prevención & control , Fitoterapia , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Células 3T3-L1 , Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Leptina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Obesidad/etiología , Tamaño de los Órganos/efectos de los fármacos , PPAR gamma/metabolismo , Extractos Vegetales/administración & dosificación , Aumento de Peso/efectos de los fármacosRESUMEN
Triticum aestivum sprouts (TA) contain significant amounts of chlorophyll, minerals, enzymes, and other functional entities. Furthermore, TA extracts have been shown to possess anti-obesity, anti-diabetic and hepatoprotective effects and are believed to help blood flow, digestion, and general detoxification of the body. In this study, the mechanism underlying the anti-cancer effects of a dichloromethane fraction of TA (TDF) was investigated in vitro and in vivo. In vitro study was done by examining cancer cells growth, morphological changes, cell cycles, expressions of death receptors and apoptosis-linked proteins in wide range of human cancer cell lines. To investigate the effect of TDF in vivo, C57BL/6 mice were injected with B16 melanoma cells and orally administered TDF. TDF markedly inhibited cancer cell growth and induced cellular morphological alterations, cell cycle arrest and apoptosis, and enhanced the expressions of death receptors (DR)-4, 5, and 6 in cell lines. In addition, TDF regulated the expressions mitochondrial apoptosis-linked proteins and induced caspase-dependent cell death. It also significantly enhanced phosphorylation of ERK1/2 and JNK, but not p38, whereas inhibited the activation of NF-κB in cancer cells. In our mouse model, TDF significantly suppressed B16 melanoma growth, to an extent similar to cisplatin (reference control) and augmented immunomodulatory cytokines. In brief, this study presents the mechanism responsible for the anti-cancer effects of TDF in vitro and in vivo.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Cloruro de Metileno/uso terapéutico , Extractos Vegetales/uso terapéutico , Plantones , Triticum , Células A549 , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Cloruro de Metileno/farmacología , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
Triticum aestivum sprout-derived polysaccharide (TASP) has anti-diabetic properties, but no information is available in regards to its protective effect against ethanol-induced hepatic injury. This study aimed to investigate the mechanism behind the protective role of TASP against ethanol-induced liver injury in vivo. Male C57BL/6 mice were administered ethanol with or without TASP for 10 consecutive days by oral gavage. Silymarin was administered in the same manner as a positive control. TASP reduced ethanol-induced hepatic lipid accumulation and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. TASP also prevented glutathione (GSH) depletion and increased the superoxide dismutase (SOD) in liver tissue. In addition, TASP significantly inhibited ethanol-induced cytochrome P450 2E1 (CYP2E1) activation, and upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and downregulated NADPH oxidase genes in ethanol fed mice. Furthermore, the upregulation of Nrf2 was found to be regulated by a phosphatidylinositol 3-kinase (PI3K)/Akt pathway. TASP also attenuated hepatic injury by modulation of caspase-3 and apoptosis-associated mitochondrial proteins including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) in liver tissues of mice. The study demonstrated that TASP treatment protects against ethanol-induced hepatic injury via multiple pathways by inhibiting steatosis and improving antioxidant marker levels during hepatic injury. Such properties provide a basis for therapeutic agents against alcohol-induced liver injury.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Polisacáridos/farmacología , Sustancias Protectoras/farmacología , Triticum/química , Alanina Transaminasa/genética , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/aislamiento & purificación , Aspartato Aminotransferasas/genética , Aspartato Aminotransferasas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Etanol/administración & dosificación , Regulación de la Expresión Génica , Glutatión/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Extractos Vegetales/química , Polisacáridos/aislamiento & purificación , Sustancias Protectoras/aislamiento & purificación , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Plantones/química , Silimarina/farmacología , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Triticum aestivum sprouts are small shoots that germinate from seeds and are consumed as a dietary supplement. The present study aimed to determine whether a dichloromethane fraction isolated from Triticum aestivum sprouts (TDF) suppressed the allergic immune response in ovalbumin (OVA)sensitized mice. In vivo experiments were performed by administering TDF or vehicle to mice during the sensitization and this was immediately followed by an intradermal injection of OVA into the ears. Splenocytes isolated from OVAsensitized mice were pretreated with TDF and rechallenged with OVA for ex vivo evaluation. Results demonstrated that TDF suppressed the inflammatory response in ear tissues and levels of total immunoglobulin (Ig)E and OVAspecific IgE in serum. TDF inhibited the production of interleukin (IL)4 and expression of GATAbinding protein3 (GATA3) transcription factor which regulates the differentiation of naïve T helper (Th) cells into Th2 cells in OVAstimulated splenocytes. TDF inhibited Th1associated cytokine interferonγ and IL12 production and downregulated the expression of Th1 specific transcription factor Tbox 21 in OVAstimulated splenocytes. Overall, these results indicated that TDF attenuates OVAinduced allergic immune response by suppressing the production of Th2 specific cytokine IL4, through inhibiting transcription factor GATA3, and suggests that TDF may exhibit the potential to regulate the immune response in allergic diseases.
Asunto(s)
Hipersensibilidad/inmunología , Inmunidad , Inmunización , Cloruro de Metileno/química , Ovalbúmina/inmunología , Células Th2/inmunología , Triticum/química , Animales , Diferenciación Celular , Separación Celular , Citocinas/metabolismo , Femenino , Inmunoglobulinas/sangre , Ratones Endogámicos BALB C , Piel/inmunología , Bazo/patología , Células TH1/inmunología , Factores de Transcripción/metabolismoRESUMEN
Hepatic injury occurs frequently during sepsis, and polysaccharides isolated from plants have been reported to have antiinflammatory and antioxidant effects in various models. However, the effect of wheatgrass-derived polysaccharide (WGP) has not been previously studied. In the present study, we investigated the effect of WGP on lipopolysaccharide (LPS)-induced hepatic injury in mice. Mice were pre-treated with WGP (100 or 200 mg/kg daily for 2 days) and then challenged with LPS (1 mg/kg, intraperitoneal), and sacrificed after 12 h. Wheatgrass-derived polysaccharide decreased serum aminotransferase levels and histological changes as compared with LPS-challenged mice. Wheatgrass-derived polysaccharide also significantly inhibited LPS-induced pro-inflammatory cytokine up-regulation and improved the oxidative status of liver tissues. Furthermore, these effects were found to be mediated by the suppression of the transcriptional activity of nuclear factor-kappa B (NF-κB), due to inhibitions of transforming growth factor beta (TGF-ß)-activated kinase (TAK)-1 phosphorylation and inhibition of kappa B (IκB)-α degradation. In addition, WGP inhibited the activations of mitogen-activated protein kinases (MAPKs). Wheatgrass-derived polysaccharide also attenuated hepatic cell death by modulating caspase-3 and apoptosis associated mitochondrial proteins, such as, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). Taken together, WGP possesses antiinflammatory, anti-oxidant and anti-apoptotic activity and ameliorates LPS-induced liver injury in mice. Copyright © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Polisacáridos/farmacología , Triticum/química , Animales , Caspasa 3/metabolismo , Citocinas/metabolismo , Lipopolisacáridos , Hígado/efectos de los fármacos , Hígado/patología , Quinasas Quinasa Quinasa PAM/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Non-small cell lung cancer (NSCLC) is the major cancer-related death worldwide with only 14% five-year survival rate. Triticumoside, a phenolic compound present in Triticum aestivum sprout extract, has been recognized to have antiobesity and anti-inflammatory effects. However, the effect of triticumoside on cancer cell proliferation and migration has not been studied. In order to elucidate whether triticumoside exhibits an anticancer effect, cells were incubated with different doses of triticumoside, and apoptosis was assessed by observing cell viability, cellular morphological changes, and annexin-V-fluorescein isothiocyanate/propidium iodide staining. Cell cycle analysis, western blotting, wound healing assay, and quantitative-polymerase chain reaction were also performed. Triticumoside exhibited marked cytotoxicity in the cells in dose- and time-dependent manner. Triticumoside caused morphological changes, including cellular rounding, nuclear condensation, and shrinkage. Likewise, triticumoside enhanced the sub-G1 proportion of cells. Additionally, triticumoside regulated expression of apoptosis-associated proteins, such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, and procaspase-3/9. Triticumoside also inhibited migration of the cells through downregulation of matrix metalloproteinase-2/9 (MMP2/9). Collectively, these results suggest that triticumoside induces apoptosis through caspase-dependent mitochondrial pathway and suppresses migration via inhibition of MMP2/9 in NSCLC A549 cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Caspasas/metabolismo , Flavonas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Fenoles/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Flavonas/química , Células HEK293 , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fenoles/química , Transducción de Señal/efectos de los fármacos , Triticum/químicaRESUMEN
Obesity is a common disease worldwide that often results in serious conditions including hypertension, diabetes, and hyperlipidemia. Many herbal medicines have been examined with regard to ameliorating obesity. We investigated the anti-obesity effects of 50% EtOH extract of Triticum aestivum sprout (TAEE) in high-fat-diet (HFD)-induced obese mice. TAEE administration (10, 50, or 200 mg/kg) for 6 weeks significantly decreased the body weights, serum total cholesterol (TC), and low-density lipoprotein cholesterol levels in HFD-fed mice. TAEE treatment reduced lipid accumulation in epididymal white adipose tissue (EWAT) and liver. Moreover, TC and lipid levels were decreased by TAEE treatment in liver. Serum leptin and adiponectin concentrations were reduced by TAEE treatment. TAEE-treated mice showed decreases in peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid synthase expression in EWAT. Furthermore, TAEE administration elevated levels of PPARα protein in the liver of HFD-induced obese mice. These results suggest that TAEE supplementation might be beneficial for the treatment and prevention of obesity and related diseases.
Asunto(s)
Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa/efectos adversos , Obesidad/dietoterapia , Extractos Vegetales/farmacología , Triticum/química , Adiponectina/sangre , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Suplementos Dietéticos , Ingestión de Alimentos/efectos de los fármacos , Leptina/sangre , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/etiología , Extractos Vegetales/análisis , Extractos Vegetales/química , Triticum/crecimiento & desarrolloRESUMEN
The present study aimed to compare the potential anti-adipogenic effects and underlying mechanisms of the luteolin, isoscoparin and isoorientin flavonoids, purified from Triticum aestivum sprout (TA) in 3T3-L1 cells. The cells were treated with different concentrations of flavonoids for 8 days and the lipid accumulation was assessed using Oil-Red-O staining. The expression levels of the transcription factors and the genes involved in adipogenesis in the cells were assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that 10 µM luteolin, isoscoparin or isoorientin inhibited lipid deposition in the cells by 74, 63 and 65%, respectively. The flavonoids also significantly inhibited the transcriptional regulators of adipogenesis, including peroxisome proliferator-activated receptor-γ, CAAT/enhancer binding protein-α and sterol regulatory element binding protein (SREBP)-1c, compared with the control cells. Similarly, there was a significant downregulation of the adipocyte specific markers associated with lipid metabolism, including activating protein-2, fatty acid synthase, hormone-sensitive lipase and lipoprotein lipase, in the flavonoid treated cells. Notably, the cells treated with the flavonoids demonstrated increased expression levels of the insulin-induced genes, insig-1 and insig-2, which may have inhibited the activation of the adipogenic transcription factor, SREBP, eventually leading to the inhibition of adipogenesis. Taken together, these results revealed that the flavonoids from TA possessed an inhibitory effect on adipogenesis through downregulation of adipogenic transcription factors and genes associated with lipid metabolism, and the upregulation of insig 1 and 2, suggesting that the flavonoids from TA may be potential therapeutic agents for the prevention and treatment of obesity.
Asunto(s)
Adipocitos/efectos de los fármacos , Diterpenos/farmacología , Luteolina/farmacología , Proteínas de la Membrana/agonistas , Triticum/química , Células 3T3-L1 , Adipocitos/citología , Adipocitos/metabolismo , Adipogénesis/efectos de los fármacos , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Diferenciación Celular , Diterpenos/aislamiento & purificación , Ácido Graso Sintasas/genética , Ácido Graso Sintasas/metabolismo , Regulación de la Expresión Génica , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Luteolina/aislamiento & purificación , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , PPAR gamma/genética , PPAR gamma/metabolismo , Transducción de Señal , Esterol Esterasa/genética , Esterol Esterasa/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismoRESUMEN
Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)- alpha, interleukin (IL)-1 beta and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF-alpha on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF- alpha inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF- alpha production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF-alpha therapeutics for several inflammatory diseases.
Asunto(s)
Colágeno Tipo I/farmacología , Células Dendríticas/inmunología , Factores Reguladores del Interferón/biosíntesis , Interleucina-12/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Diferenciación Celular/genética , Células Cultivadas , Regulación hacia Abajo , Femenino , Interleucina-1beta , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , Regulación hacia ArribaRESUMEN
In this report, we investigated the anti-obesity effect of wheat sprouts and their component compounds. Twenty compounds (1-20) were isolated from Triticum aestivum. Among them, glycolipids 1-5 were determined for the first time from T. aestivum and its sprouts. The HPLC analysis demonstrated that compounds 1-3, 5, 8, 12, and 14 were major peak in the HPLC chromatogram of the active fraction. The effects of the compounds on lipid accumulation were assessed at concentrations ranging from 1.0 to 100 µM. At concentration of 10.0 µM, compounds 1-7, 10-15, and 17-19 significantly decreased lipid accumulation in 3T3-L1 preadipocytes. Glycolipids 1, 2, and phenolic 17 significantly reduced lipid accumulation in the differentiated adipocytes in a concentration-dependent manner. Quantitative analysis based on measurement of the optical density of Oil Red O indicated that, at 100 µM, compounds 1, 2, and 17 reduced lipid accumulation by 41, 37, and 48%, respectively, compared with the positive control.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Triticum/química , Células 3T3 , Animales , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Glucolípidos/aislamiento & purificación , Glucolípidos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Ratones , Fenoles/aislamiento & purificación , Fenoles/farmacología , PlantonesRESUMEN
Dioscin (DS) is a steroidal saponin present in a number of medicinal plants and has been shown to exert anticancer, antifungal and antiviral effects. The present study aimed to deternube the effects DS on the regulation of adipogenesis and to elucidate the underlying mechanisms. In vitro experiments were performed using differentiating 3T3-L1 cells treated with various concentrations (0-4 µM) of DS for 6 days. A cell viability assay was performed on differentiating cells following exposure to DS. Oil Red O staining and triglyceride content assay were performed to evaluate the lipid accumulation in the cells. We also carried out the following experiments: i) flow cytometry for cell cycle analysis, ii) quantitative reverse transcription polymerase chain reaction for measuring adipogenesis-related gene expression, and iii) western blot analysis to measure the expression of adipogenesis transcription factors and AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase (MAPK) phosphorylation. In vivo experiements were performed using mice with obesity induced by a high-fat diet (HFD) that were treated with or without DS for 7 weeks. DS suppressed lipid accumulation in the 3T3-L1 cells without affecting viability at a dose of up to 4 µM. It also delayed cell cycle progression 48 h after the initiation of adipogenesis. DS inhibited adipocyte differentiation by the downregulation of adipogenic transcription factors and attenuated the expression of adipogenesis-associated genes. In addition, it enhanced the phosphorylation of AMPK and its target molecule, ACC, during the differentiation of the cells. Moreover, the inhibition of adipogenesis by DS was mediated through the suppression of the phosphorylation of MAPKs, such as extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). DS significantly reduced weight gain in the mice with HFD-induced obesity; this was evident by the suppression of fat accumulation in the abdomen. the present study reveals an anti-adipogenic effect of DS in vitro and in vivo and highlights AMPK/MAPK signaling as targets for DS during adipogenesis.
Asunto(s)
Adipogénesis/efectos de los fármacos , Diosgenina/análogos & derivados , Transducción de Señal , Aumento de Peso/efectos de los fármacos , Células 3T3-L1 , Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Composición Corporal/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Diosgenina/farmacología , Regulación hacia Abajo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Triglicéridos/metabolismoRESUMEN
The present study investigated the role of extracellular signal-regulated kinase (ERK) activation in the migratory phenotype of human U2OS osteosarcoma (OS) cells in a collagen matrix. The activation of ERK was inhibited by PD98059, a specific inhibitor of ERK kinase. Additionally, no significant differences were observed in the adhesion and proliferation of the cells with or without PD98059 treatment in collagen-coated dishes. The migratory capacity of the U2OS cells was then examined in non-coated and collagen-coated dishes, and the results depicted that collagen I enhanced the migration of the U2OS cells, the effect of which was significantly blocked by the treatment of the cells with PD98059. Furthermore, enhanced gene and protein expression of matrix metalloproteinase 9 (MMP9), but not MMP2, was observed to be involved in the enhanced migratory phenotype of the U20S cells in the collagen-coated plates. This effect was partially abolished by the treatment of the cells in the collagen-coated dishes with ERK inhibitor. Collectively, the data demonstrate that ERK signaling is important for the migration of U2OS cells through the extracellular matrix (ECM), which is comprised mostly of collagen, by enhancing MMP9 production. These results may contribute to the regulation of MMP9 production in metastatic OS.
RESUMEN
We investigated the mechanism involving discoidin domain receptor 2 (DDR2) mediated production of interleukin 12 (IL-12). When compared to control, collagen I upregulated the IL-12 luciferase activity on DDR2 expressing cells. Collagen I induced the phosphorylation of DDR2 and enhanced the phosphorylation of mitogen activated protein kinase (MAPK) kinases. In addition, NF-κB binding activity was enhanced when the cells expressing NF-κB reporter were exposed to collagen I. Moreover, when IL-12 reporter transfected cells were treated with biochemical inhibitors of c-Jun N-terminal kinase (JNK) and NF-κB, collagen-induced IL-12 promoter activity was significantly downregulated in comparison to non-treated cells. Similarly, confirmatory experiments on murine dendritic cells revealed that IL-12 promoter activity is dose dependently downregulated upon NF-κB and JNK inhibitor treatment on collagen I stimulation. In summary, DDR2 is involved in the collagen I-induced IL-12 production via NF-κB and JNK pathway.