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1.
Plants (Basel) ; 9(12)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287317

RESUMO

Toona sinensis has been traditionally used to treat dysentery, enteritis, flatulence, and itchiness. However, the existence of anti-inflammatory effects of T. sinensis on Propionibacterium acnes-induced skin disease is unknown. In vitro cultures of plant cells and tissues produced under controlled conditions offer a continuous production platform for plant natural products including pigments and anti-inflammatory agents. In this study, we determine the anti-inflammatory activities of an extract of in vitro grown adventitious shoots of T. sinensis on P. acnes, the etiologic agent of skin inflammation. The extract of T. sinensis showed antioxidant and anti-inflammatory activity in LPS-treated RAW264.7 cells. It also had antibacterial activity and anti-inflammatory effects on P. acnes-treated HaCaT cells. In addition, these effects were regulated by suppression of the mitogen-activated protein kinase (MAPK) pathways. These results suggesting the potential application of adventitious shoots of T. sinensis grown with an in vitro proliferation system as a medicine for treating P. acnes-induced inflammatory skin disease.

2.
Nat Prod Res ; : 1-3, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419489

RESUMO

To enhance the skin whitening effect, tyrosinase activity and melanin biosynthesis needs to be suppressed in the skin. To achieve this goal, we examined the extract of Thymus quinquecostatus flowers, and identified a functional ingredient, galuteolin. Galuteolin effectively inhibited melanin biosynthesis in B16/F10 cells, partially suppressing tyrosinase activity. Therefore, this study suggests that galuteolin can be used as a cosmetic ingredient for skin whitening.

4.
Nutrients ; 11(10)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614689

RESUMO

Chronic and extensive exposure of ultraviolet (UV)-irradiation causes human skin sunburn, inflammation, or photoaging, which is associated with downregulated collagen synthesis. This study investigated the effects of fermented blackberry (Rubus fruticosus B., FBB) by Lactobacillus plantarum JBMI F5 (LP) on UVB-induced photoaging in human foreskin fibroblast (Hs68) as well as in SKH-1 hairless mice. FBB pretreatment inhibited UVB-mediated type-1 procollagen degradation, matrix metalloproteinase (MMP)-1 and MMP-2 protein expression, and suppressed nuclear factor-κB (NF-κB) activation as well as mitogen-activated protein kinase (MAPK) phosphorylation in Hs68. In addition, FBB administration diminished the wrinkle formation in dorsal skin and epidermal thickening in UVB-irradiated hairless mice. Moreover, UVB-induced Type-1 procollagen reduction and antioxidant enzyme inactivation were reversed by FBB administration. These results suggest that FBB may have antiphotoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of reactive oxygen species and related MAPK and NF-κB signaling. Therefore, FBB can be a potential candidate for protecting skin aging against UV irradiation.


Assuntos
Fibroblastos/efeitos dos fármacos , Lactobacillus plantarum/metabolismo , Extratos Vegetais/farmacologia , Rubus/química , Envelhecimento da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Fermentação , Fibroblastos/efeitos da radiação , Prepúcio do Pênis/citologia , Frutas/química , Masculino , Camundongos , Camundongos Pelados , Extratos Vegetais/química , Envelhecimento da Pele/efeitos da radiação
7.
Nat Prod Res ; 33(22): 3283-3286, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29726712

RESUMO

In this study, Auricularia auricula-judae (Bull.) extract (AAE) had potent antioxidant activity in vitro and promoted the biosynthesis of procollagen, a precursor of collagen in HaCaT cells. In addition, the expression of HAS-3 (hyaluronic acid synthase), which is a moisturizing factor, was increased in HaCaT cells in response to AAE. Therefore, this work suggests that AAE has the potential to exhibit antioxidant activity and promote procollagen biosynthesis in HaCaT cells.


Assuntos
Agaricales/química , Antioxidantes/isolamento & purificação , Pró-Colágeno/biossíntese , Antioxidantes/química , Antioxidantes/farmacologia , Basidiomycota , Linhagem Celular , Humanos , Hialuronan Sintases/efeitos dos fármacos , Hialuronan Sintases/metabolismo , Pró-Colágeno/efeitos dos fármacos , Pele/citologia , Pele/enzimologia , Pele/metabolismo
8.
Nutr Res Pract ; 12(1): 20-28, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29399293

RESUMO

BACKGROUND/OBJECTIVES: Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced ß-cell damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS: Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS: The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS: Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.

9.
Nutrients ; 9(3)2017 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-28300786

RESUMO

Growing evidence has indicated that supplementation with probiotics improves lipid metabolism. We aimed to investigate the beneficial effects of a probiotics mixture (PM) of three strains belonging to the species Bifidobacterium (B. longum, B. lactis, and B. breve) and two strains belonging to the species Lactobacillus (L. reuteri and L. plantarum) on cholesterol-lowering efficacy in hypercholesterolemic rats. A hypercholesterolemic rat model was established by feeding a high-cholesterol diet for eight weeks. To test the effects of PM on hypercholesterolemia, hypercholesterolemic rats were assigned to four groups, which were treated daily with low (1.65 × 108 cfu/kg), medium (5.5 × 108 cfu/kg), or high (1.65 × 1010 cfu/kg) doses of probiotic mixture or simvastatin for eight weeks. Significant reductions of serum total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein (LDL)-cholesterol levels, but increases of high-density lipoprotein (HDL)-cholesterol were observed after supplementation of PM in hypercholesterolemic rats. In PM-supplemented hypercholesterolemic rats, hepatic tissue contents of TC and TG also significantly decreased. Notably, the histological evaluation of liver tissues demonstrated that PM dramatically decreased lipid accumulation. For their underlying mechanisms, we demonstrated that PM reduced expressions of cholesterol synthesis-related proteins such as sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in the liver. Taken together, these findings suggest that PM has beneficial effects against hypercholesterolemia. Accordingly, our PM might be utilized as a novel therapeutic agent for the management of hypercholesterolemia.


Assuntos
Hipercolesterolemia/terapia , Probióticos/administração & dosagem , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bifidobacterium/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Ácido Graxo Sintases/metabolismo , Hipercolesterolemia/sangue , Lactobacillus/metabolismo , Fígado , Masculino , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/sangue
10.
Biomed Res Int ; 2015: 283630, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26357651

RESUMO

The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. In a continuing search for compounds with antibacterial activity against several microorganisms including S. aureus and MRSA, an n-hexane extract of Magnolia officinalis was found to contain magnolol. This compound exhibited potent activity against S. aureus, standard methicillin-susceptible S. aureus (MSSA), and MRSA as well as clinical MRSA isolates. When combined with oxacillin, the antibacterial activities of magnolol and honokiol against the MRSA strain were increased compared to single treatment without antibiotics at 10 µg/mL and 25 µg/mL, respectively. These activities of magnolol and honokiol were dose dependent. Also, magnolol showed synergistic effects with oxacillin against 13 clinical isolates of MRSA. It was determined that magnolol and honokiol had a synergistic effect with oxacillin against MRSA strain. Furthermore, the magnolol inhibited the expression of the resistant genes, mecA, mecI, femA, and femB, in mRNA. We concluded that the antibacterial activity of magnolol against MRSA strain is more related to the mecI's pathway and components of the cell wall than mecR1. Therefore, the results obtained in this study suggest that the combination of magnolol and antibiotics could lead to the development of new combination antibiotics against MRSA infection.


Assuntos
Anti-Infecciosos/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Hexanos/química , Testes de Sensibilidade Microbiana/métodos , Oxacilina/farmacologia , Extratos Vegetais/farmacologia
11.
FEBS Lett ; 589(7): 836-41, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25728277

RESUMO

Tmem173 was identified as a growth inhibitor associated with major histocompatibility complex (MHC) class II and a potential stimulator for IFN-ß, an innate immune inducer and a negative feedback controller for RANKL-induced osteoclast differentiation of monocytic macrophage cells. In this study, we confirmed that transmembrane protein 173 (Tmem173) overexpression inhibited the expression of osteoclast-specific genes, tartrate-resistant acid phosphatase (TRAP), cathepsin K, and matrix metalloproteinase-9 (MMP-9), as well as bone resorption pit formation in RANKL-treated RAW 264.7 cells. Activation of osteoclast-specific transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic-1 (NFATc1), and RANKL-induced activation of ERK were also down-regulated by Tmem173 overexpression. Collectively, these results suggest that Tmem173 plays a regulatory role in RANKL-RANK-mediated signaling in osteoclastogenesis.


Assuntos
Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Regulação da Expressão Gênica , Camundongos , Osteoclastos/citologia , Osteoprotegerina/metabolismo , Ligante RANK/genética , Transdução de Sinais
12.
J Med Food ; 18(4): 421-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25658580

RESUMO

Red ginseng (Panax ginseng C.A. Meyer) is the most widely recognized medicinal herb due to its remedial effects in various disorders, such as cancers, diabetes, and heart problems. In this study, we investigated the anticancer effect of fermented red ginseng extract (f-RGE; provided by Jeonju Biomaterials Institute, Jeonju, South Korea) in a parallel comparison with the effect of nonfermented red ginseng extract (nf-RGE; control) on several cancer cell lines--MCF-7 breast cancer cells, HepG2 hepatocellular carcinoma cells, and reprogrammed MCF-7 cells (mimicking cancer stem cells). Cells were cultured at various concentrations of RGE (from 0.5 up to 5 mg/mL) and their viabilities and proliferative properties were examined. Our data demonstrate the following: (1) nf-RGE inhibited cell viability at ≥1 mg/mL for MCF-7 cells and ≥2 mg/mL for HepG2 cells, (2) in the presence of a carcinogenic agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), nf-RGE treatment in combination with paclitaxel synergistically decreased MCF-7 as well as HepG2 cell viability, (3) f-RGE (which contained a greater level of Rg3 content) more effectively decreased the viability of MCF-7 and HepG2 cells compared to nf-RGE, and (4) f-RGE appeared more potent for inhibiting cancerous differentiation of reprogrammed MCF-7 cells in a synergistic fashion with paclitaxel, especially in the presence of TPA, compared to nf-RGE. These findings suggest that f-RGE treatment may be more effective for decreasing cancer cell survival by inducing apoptotic cell death and also presumably for preventing cancer stem cell differentiation compared to nf-RGE.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lactobacillus rhamnosus/metabolismo , Panax/química , Panax/microbiologia , Extratos Vegetais/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Fermentação , Células Hep G2 , Humanos , Panax/metabolismo , Extratos Vegetais/química , Extratos Vegetais/metabolismo , República da Coreia
13.
J Biosci Bioeng ; 119(4): 433-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25454694

RESUMO

Biosorption of heavy metals and dyes is a promising technology that involves the removal of toxic metals from industrial wastes. The present study aims to screen the bacterial strains isolated from soils and polluted pond for their potential biosorption of both cationic dye and cadmium. Bacillus catenulatus JB-022 strain removed 58% and 66% of cationic basic blue 3 (BB3) and cadmium (Cd(II)) at the respective concentrations of 2000 mg/L and 150 mg/L. The biosorption equilibrium data were well fitted by the Langmuir adsorption isotherm, and the kinetic studies indicated that the biosorption followed the pseudo-second-order model. The biosorption kinetics showed that the equilibrium was reached within 10 min and 5 min for BB3 and Cd(II), respectively. According to the Langmuir model, the maximum uptakes of BB3 and Cd(II) by the JB-022 biomass were estimated to be 139.74 and 64.28 mg/g, respectively. To confirm the surface morphology and functional groups, field emission scanning electron microscope, energy-dispersive X-ray spectrometer, X-ray diffraction, and Fourier transform infrared spectroscopy analyses were carried out, and the results revealed that the biomass of JB-022 has carboxyl and phosphonate groups as potential surface functional groups capable of binding to cationic pollutants. In conclusion, B. catenulatus JB-022 is proposed as an excellent biosorbent with potentially important applications in removal of cationic pollutants from wastewaters.


Assuntos
Bacillus/metabolismo , Cádmio/isolamento & purificação , Cádmio/metabolismo , Corantes/metabolismo , Adsorção , Bacillus/classificação , Biomassa , Cádmio/toxicidade , Cátions/isolamento & purificação , Cátions/metabolismo , Cátions/toxicidade , Corantes/química , Precipitação Fracionada , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Águas Residuárias/química , Difração de Raios X
14.
Life Sci ; 108(2): 94-103, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-24880074

RESUMO

AIMS: We studied that a potent antifibrotic effect of decursin on in vivo liver damage model and the mechanism in inhibiting which transforming growth factor (TGF)-ß1-induced human hepatic stellate cells (HSCs) activation. MAIN METHODS: Liver injury was induced in vivo by intraperitoneal injection of carbon tetrachloride (CCl4) with or without decursin for 4weeks in mice. Human hepatic stellate cell line, an immortalized human HSC line, was used in in vitro assay system. The effects of decursin on HSC activation were measured by analyzing the expression of α-smooth muscle actin (α-SMA) and collagen I in liver tissue and human HSCs. KEY FINDINGS: Decursin treatment significantly reduced the ratio of liver/body weight, α-SMA activation, and type I collagen overexpression in CCl4 treated mice liver. The elevated serum levels, including ALT, AST, and ALP, were also decreased by decursin treatment. Treatment of decursin markedly proved the generation of reactive oxygen species, NAD(P)H oxidase (NOX) protein (1, 2, and 4) upregulation, NOX activity, and superoxide anion production in HSCs by TGF-ß1. It also significantly reduced TGF-ß1-induced Smad 2/3 phosphorylation, nuclear translocation of Smad 4, and association of Smad 2/3-Smad 4 complex. Consistent with in vitro results, decursin treatment effectively blocked the levels of NOX protein, and Smad 2/3 phosphorylation in injured mice liver. SIGNIFICANCE: Decursin blocked CCl4-induced liver fibrosis and inhibited TGF-ß1-mediated HSC activation in vitro. These data demonstrated that decursin exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-ß1 induced NOX activation and Smad signaling.


Assuntos
Benzopiranos/farmacologia , Butiratos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , NADPH Oxidases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/administração & dosagem , Regulação para Cima/efeitos dos fármacos
15.
Food Chem Toxicol ; 50(3-4): 1045-53, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22138248

RESUMO

High glucose (HG) is the underlying factor contributing to long term complication of diabetes mellitus. Reactive oxygen species (ROS) have been postulated as a unifying mechanism for HG-induced complications. NADPH oxidase, producing superoxide anion, is the main source of ROS in diabetic nephropathy. In this study we report the inhibitory effect of schizandrin (Sch), an active ingredient of Fructus schisandrae, on HG-induced murine mesangial cells (MMCs) damage. Sch treatment significantly attenuated HG-induced proliferation and protein synthesis of MMCs in a dose dependent manner. The intracellular reactive oxygen species (ROS) level was also remarkably reduced by Sch as well as the enhanced NADPH oxidase activity, superoxide anion levels, NOX4 and p22phox protein expression, and phosphorylation of p47phox and p67phox. The phosphorylation level of mitogen activated kinase (MAPK) protein, phospho-Erk1/2 and -p38, and Akt was also significantly inhibited by Sch under HG condition. By using specific inhibitors, we found that Sch inhibits HG-induced mesangial cell proliferation and ECM overexpression via NADPH oxidase/PI3K-Akt-MAPK-dependent pathway in MMCs. Taken together; our demonstration of the ability of Sch to inhibit high glucose induced damage of MMCs has clinical implications in treatment of diabetic nephropathy.


Assuntos
Ciclo-Octanos/farmacologia , Mesângio Glomerular/efeitos dos fármacos , Lignanas/farmacologia , NADPH Oxidases/antagonistas & inibidores , Compostos Policíclicos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Mesângio Glomerular/citologia , Mesângio Glomerular/enzimologia , Mesângio Glomerular/metabolismo , Glucose/farmacologia , Sistema de Sinalização das MAP Quinases , Camundongos , Fosforilação , Fator de Crescimento Transformador beta1/metabolismo
16.
Molecules ; 15(10): 7395-402, 2010 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-20966880

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) has been emerging worldwide as one of the most important problems in communities and hospitals. Therefore, new agents are needed to treat acute oral infections from MRSA. In this study, antibacterial compounds from the roots of Atractylodes japonica (A. japonica) were isolated and characterized. The compounds were isolated from the root extracts using HPLC-piloted activity-guided fractionations. Four A. japonica compounds were isolated and identified as atractylenolide III (1), atractylenolide I (2), diacetylatractylodiol [(6E,12E)-tetradeca-6,12-diene-8,10-diyne-1,3-diol diacetate, TDEYA, 3). and (6E,12E)-tetradecadiene-8,10-diyne-1,3-diol (TDEA, 4), which was obtained by hydrolysis of TDEYA. The minimum inhibitory concentrations (MICs) was determined in the setting of clinical MRSA isolates. Compound 4 showed anti-MRSA activity with a MIC value of 4-32 µg/mL. The overall results provide promising baseline information for the potential use of the extract of A. japonica as well as some of the isolated compounds in the treatment of bacterial infections.


Assuntos
Antibacterianos , Atractylodes/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/química , Infecções Estafilocócicas/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Atractylodes/anatomia & histologia , Humanos , Estrutura Molecular , Raízes de Plantas/química
17.
Microb Pathog ; 47(1): 47-51, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19447166

RESUMO

Endothelial hyperpermeability, a hallmark of septicemia, is induced by stress fiber formation, which is primarily regulated by the calcium/calmodulin signaling pathway in endothelial cells. We previously reported that trifluoperazine, a calcium/calmodulin antagonist, blocks Vibrio vulnificus cytolysin (VVC) -induced lethality at in vivo animal model. The object of this study was therefore to examine whether VVC induces stress fiber formation through calcium/calmodulin signaling in endothelial cells. Here, we monitored calcium-influx after treatment of VVC using confocal microscopy in CPAE cells, pulmonary endothelial cell line. Interestingly, we found that VVC-induced dose-dependently increases of [Ca(2+)](i) in CPAE cells. Moreover, VVC-induced stress fiber formation as well as phosphorylation of myosin light chain (MLC) in a dose- and time-dependent manner, which was completely blocked by trifluoperazine. These results suggest that the calcium/calmodulin signaling pathway plays a pivotal role in VVC-induced hyperpermeability.


Assuntos
Toxinas Bacterianas/toxicidade , Cálcio/metabolismo , Calmodulina/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Perforina/toxicidade , Transdução de Sinais/efeitos dos fármacos , Vibrio vulnificus/fisiologia , Animais , Bovinos , Linhagem Celular , Células Endoteliais/microbiologia , Cadeias Leves de Miosina/metabolismo , Fosforilação , Fibras de Estresse/metabolismo
18.
Metabolism ; 54(3): 314-20, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15736108

RESUMO

Resistin is a protein secreted from adipose tissue that is thought to play a role in insulin sensitivity. We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus who showed poor glycemic control with glimepiride (4 mg/d) were randomized to rosiglitazone (4 mg/d) and metformin (500 mg bid) treatment groups. All subjects continued glimepiride treatment as well. The plasma concentrations of resistin were measured at baseline and at 6 months of treatment for both groups. The anthropometric parameters, fasting plasma glucose, HbA1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, free fatty acids, and adiponectin concentrations were also measured. After 6 months of treatment, the reduction in plasma glucose levels was similar between the 2 groups. There were no significant changes in the lipid profiles of either group during the study period. The plasma resistin levels decreased in the rosiglitazone group (2.49 +/- 1.93 vs 1.95 +/- 1.59 ng/ml; P < .05) but increased in the metformin group (2.61 +/- 1.69 vs 5.13 +/- 2.81 ng/ml; P < .05). The plasma adiponectin concentrations were increased in the rosiglitazone group (2.91 +/- 1.46 vs 4.23 +/- 1.77 microg/ml; P < .05) but were unchanged in the metformin group. In summary, rosiglitazone treatment decreased the plasma resistin levels whereas metformin treatment increased them in patients with type 2 diabetes mellitus showing poor glycemic control with sulfonylurea therapy. These results suggest that the observed changes in plasma resistin levels are not the consequences of improved insulin resistance, nor are they consequences of glycemic control. Considering the potential role of resistin in insulin resistance, decrease in resistin levels may contribute to improving insulin action with rosiglitazone treatment.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hormônios Ectópicos/sangue , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Tiazolidinedionas/farmacologia , Adiponectina , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobina A Glicada/análise , Homeostase , Humanos , Resistência à Insulina , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Resistina , Rosiglitazona , Tiazolidinedionas/uso terapêutico
19.
Mol Endocrinol ; 18(5): 1082-95, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-14963109

RESUMO

The orphan nuclear receptors small heterodimer partner (SHP) and dosage-sensitive sex-reversal adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1 (DAX-1) contain extra amino acids between helices H6 and H7 of LBD, and here we investigated a possible role of these additional amino acids. Transient transfection assay demonstrated that, in contrast to wild type, in mutant SHP Delta128-139 deletion of 12 extra amino acids in H6-H7 failed to repress the transactivity of orphan nuclear receptors such as estrogen receptor-related receptor-gamma, hepatocyte nuclear factor 4alpha, and constitutive androstane receptor. Interestingly, yeast two-hybrid and glutathione-S-transferase pull-down assays demonstrated that wild-type and SHP Delta128-139 have similar abilities to interact with estrogen receptor-related receptor-gamma, hepatocyte nuclear factor 4alpha, and constitutive androstane receptor. Unexpectedly, in wild-type DAX-1 and mutant DAX-1 Delta338-362, deletion of 25 extra amino acids in H6-H7 had no significant difference in the interaction and repression of steroidogenic factor 1 transactivation. Mutant SHP that contains DAX-1 extra amino acids or polyalanine stretch in H6-H7 showed indistinguishable pattern of repression from wild-type SHP. Interestingly, the swapped SHP mutant with DAX-1 extra amino acids interacted with EID-1 (E1A-like inhibitor of differentiation 1), which is characterized as an SHP-interacting corepressor. However, interaction between SHP Delta128-139 and EID-1 was significantly diminished. Moreover, SHP-mediated repression of constitutive androstane receptor transactivation was significantly released by down-regulation of EID-1 expression with EID-1 small interfering RNA. The present study suggests that H6-H7 loop regions of SHP and DAX-1 play a different role in the repression of nuclear receptor transactivation.


Assuntos
Proteínas de Ligação a DNA/genética , Modelos Moleculares , Receptores Citoplasmáticos e Nucleares/genética , Receptores do Ácido Retinoico/genética , Proteínas Repressoras/genética , Cromossomo X/genética , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Receptor Nuclear Órfão DAX-1 , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Humanos , Dados de Sequência Molecular , Mutação/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores do Ácido Retinoico/metabolismo , Proteínas Repressoras/metabolismo , Fator Esteroidogênico 1 , Transativadores/genética , Transcrição Genética , Células Tumorais Cultivadas , Cromossomo X/metabolismo
20.
J Clin Endocrinol Metab ; 89(1): 150-6, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14715842

RESUMO

Resistin is an adipocyte-derived peptide that might play a role in obesity and insulin resistance. However, its role in humans is largely unclear. Although many studies have measured the expression of human resistin in tissues, the circulating concentrations of resistin and its relation to metabolic parameters in humans are unknown. We developed an ELISA for human resistin and measured plasma concentrations in aged individuals with or without type 2 diabetes mellitus. To validate the results of plasma resistin concentrations in our subjects, plasma adiponectin concentrations were also determined, which were higher in nondiabetic subjects than in type 2 diabetic patients and correlated with the homeostasis model assessment for insulin resistance (HOMA-IR). Log-transformed plasma resistin concentrations (log-resistin) were higher in diabetic patients compared with normal individuals (0.50 +/- 0.39 vs. 0.28 +/- 0.51 ng/ml; P < 0.001), and this difference was significant after controlling for gender and body mass index. Log-resistin did not show a significant correlation with HOMA-IR, waist circumference, body mass index, blood pressure, or total cholesterol. The plasma glucose concentration was an independent factor associated with log-resistin. In conclusion, plasma resistin concentrations are elevated in patients with type 2 diabetes, but are not associated with insulin resistance or obesity.


Assuntos
Anticorpos Monoclonais , Diabetes Mellitus Tipo 2/sangue , Ensaio de Imunoadsorção Enzimática , Hormônios Ectópicos/sangue , Idoso , Glicemia/análise , Pressão Sanguínea , Constituição Corporal , Índice de Massa Corporal , Colesterol/sangue , Feminino , Homeostase , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Resistina
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