RESUMO
Pruni Cortex is a herbal drug from the bark of the Japanese flowering cherries, Prunus jamasakura or Prunus verecunda, and is included in the traditional Japanese herbal (Kampo) formula Jumihaidokuto, which is administered orally to patients suffering from inflammatory skin diseases. The flavanones contained in Pruni Cortex (e.g., sakuranetin and naringenin) have potent anti-inflammatory, anti-allergic, and anti-microbial activities. Although the effects of Pruni Cortex on skin disease have been well studied, reports regarding its pharmacological effects on the liver are limited. In this study, we extracted the bark of Prunus jamasakura and purified it to isolate the pharmacologically active constituents by monitoring nitric oxide (NO) production in rat hepatocytes that were treated with the pro-inflammatory cytokine, interleukin (IL)-1ß. Sakuranetin and (-)-naringenin, which were present in an ethyl acetate-soluble fraction of the bark extract, significantly inhibited NO induction and inducible nitric oxide synthase (iNOS) expression. These two flavanones decreased the expression of type 1 IL-1 receptor gene and phosphorylation of Akt, also known as protein kinase B, which is regulated by phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Furthermore, sakuranetin decreased the phosphorylation of the activator isoforms of CCAAT/enhancer-binding protein ß (C/EBPß), which synergistically activates the transcription of the iNOS gene with nuclear factor κB (NF-κB). Therefore, sakuranetin inhibited the co-activating activity of C/EBPß with NF-κB, leading to the suppression of iNOS gene expression in hepatocytes. Taken together, sakuranetin in Pruni Cortex downregulated the iNOS gene by inhibiting PI3K/Akt signal transduction and the phosphorylation of C/EBPß. These results imply that sakuranetin may be primarily responsible for the anti-inflammatory effects of Pruni Cortex in the liver.
Assuntos
Flavanonas/farmacologia , Flavonoides/farmacologia , Hepatócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Prunus/química , Animais , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Citocinas/metabolismo , Regulação para Baixo , Flavanonas/isolamento & purificação , Flavonoides/isolamento & purificação , Hepatócitos/metabolismo , Humanos , Interleucina-1beta , Fígado/efeitos dos fármacos , Masculino , Medicina Kampo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Casca de Planta/química , Extratos Vegetais/química , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Receptores de Interleucina-1/antagonistas & inibidores , Transdução de SinaisRESUMO
Obesity is highly correlated with several metabolic disorders. Adipocyte differentiation is a key process in determining obesogenesis. 14-Deoxy-11,12-didehydroandrographolide (deAND) is a diterpenoid rich in Andrographis paniculata (Burm.f.) Nees., a herbal medicine commonly used to treat colds, infections, and liver diseases. We investigated whether deAND inhibits the adipogenesis of 3T3-L1 cells and the underlying mechanisms. We found that deAND (0-15⯵M) dose-dependently inhibits the mRNA and protein expression of peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1c, fatty acid synthase, and stearoyl-CoA desaturase-1. Cellular lipid accumulation was decreased by deAND, and the early phase of adipocyte differentiation was critical for this inhibition. Immunoblotting revealed that deAND attenuated differentiation medium-induced protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation, which leads to down-regulating C/EBPß transcription. Moreover, deAND inhibited ERK- and GSK3ß-mediated C/EBPß transcriptional activity. Flow cytometry analysis showed that deAND impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the G0/G1 phase, while the expression of cyclin D1, cyclin E, CDK6, and CDK2 was attenuated. deAND increased the phosphorylation of AMPK and raptor, an mTOR-interacting partner, which inhibited the mTOR-driven phosphorylation of P70S6K and eukaryotic translation initiation factor 4E binding protein. In the presence of compound C, deAND modulation of AMPK-mTOR signaling and inhibition of cell cycle regulator expression were reversed. Our results reveal that the anti-adipogenic effect of deAND is likely through inhibition of the PKA-CREB-C/EBPß and AMPK/mTOR pathways, which leads to down-regulating C/EBPß-driven lipogenic protein expression and halting MCE progression.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Diterpenos/farmacologia , Mitose/efeitos dos fármacos , Células 3T3-L1 , Ativação Metabólica/efeitos dos fármacos , Andrographis/química , Animais , Células Clonais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacosRESUMO
Although epidemiological data have indicated that a strong negative association exists between coffee consumption and the prevalence of obesity-associated diseases, the molecular mechanisms by which coffee intake prevents obesity-associated diseases has not yet been elucidated. In this study, we found that coffee intake significantly suppressed high-fat diet (HFD)-induced metabolic alternations such as increases in body weight and the accumulation of adipose tissue, and up-regulation of glucose, free fatty acid, total cholesterol and insulin levels in the blood. We also found that coffee extract significantly inhibited adipogenesis in 3T3-L1 preadipocytes. In the early phase of adipogenesis, 3T3-L1 cells treated with coffee extract displayed the retardation of cell cycle entry into the G2/M phase called as mitotic clonal expansion (MCE). Coffee extract also inhibited the activation of CCAAT/enhancer-binding protein ß (C/EBPß) by preventing its phosphorylation by ERK. Furthermore, the coffee extract suppressed the adipogenesis-related events such as MCE and C/EBPß activation through the down-regulation of insulin receptor substrate 1 (IRS1). The stability of the IRS1 protein was markedly decreased by the treatment with coffee extract due to proteasomal degradation. These results have revealed an anti-adipogenic function for coffee intake and identified IRS1 as a novel target for coffee extract in adipogenesis.
Assuntos
Adipogenia/efeitos dos fármacos , Café/química , Proteínas Substratos do Receptor de Insulina/genética , Insulina/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Glicemia/análise , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Café/metabolismo , Dieta Hiperlipídica , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos não Esterificados/sangue , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/patologia , Obesidade/prevenção & controle , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Triglicerídeos/sangueRESUMO
Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0-15µM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPß mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPß expression. In addition, ERK and GSK3ß-dependent C/EBPß phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPß expression as well as C/EBPß transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression.
Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Diterpenos/farmacologia , Células 3T3-L1 , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Camundongos , PPAR gama/metabolismoRESUMO
Zanthoxylum schinifolium is widely used as a food flavoring in east Asia. Although this plant has also been used in traditional oriental medicine for the treatment of the common cold, toothache, stomach ache, diarrhea and jaundice, its anti-obesity activity remains to be elucidated. The present study investigated the effects of ethanol extract from the leaves of Z. schinifolium (EEZS) on adipocyte differentiation, and its underlying mechanism, in 3T3-L1 pre-adipocytes. The results demonstrated that EEZS effectively suppressed intracellular lipid accumulation at non-toxic concentrations, and was associated with the downregulation of several adipocyte-specific transcription factors, including peroxisome proliferation-activity receptor γ (PPARγ), CCAAT/enhancer binding protein (C/EBP)α and C/EBPß, in a concentration-dependent manner. Furthermore, it was observed that EEZS markedly inactivated the extracellular signal-regulated protein kinase (ERK) and phosphatidylinositide 3-kinase (PI3K)/Akt pathways, which act upstream of PPARγ and C/EBPs in adipogenesis. These results suggested that EEZS inhibited lipid accumulation by downregulating the major transcription factors involved in the pathway of adipogenesis, including PPARγ, C/EBPα and C/EBPß, via regulation of the ERK and PI3K/Akt signaling pathways in 3T3-L1 adipocyte differentiation. This indicated the potential use of EEZS as an anti-obesity agent.
Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/genética , Fosfatidilinositol 3-Quinases/genética , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Zanthoxylum/química , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Animais , Fármacos Antiobesidade/química , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/antagonistas & inibidores , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etanol , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Camundongos , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , SolventesRESUMO
This study examined the anti-obesity effect and mechanism of action of blueberry peel extracts (BPE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. The levels of lipid accumulation were measured, along with the changes in the expression of genes and proteins associated with adipocyte differentiation in 3T3-L1 cells. Evidenced by Oil-red O staining and triglyceride assay, BPE dose-dependently inhibited lipid accumulation at concentrations of 0, 50, and 200 µg/ml. BPE decreased the expression of the key adipocyte differentiation regulator C/EBPß, as well as the C/EBPα and PPARγ genes, during the differentiation of preadipocytes into adipocytes. Moreover, BPE down-regulated adipocyte-specific genes such as aP2 and FAS compared with control adipocytes. The specific mechanism mediating the effects of BP revealed that insulin-stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3ß, was downregulated by BPE treatment in 3T3-L1 cells. Together, these data indicated that BP exerted anti-adipogenic activity by inhibiting the expression of PPARγ and C/EBPß and the Akt signaling pathway in 3T3-L1 adipocytes. Next, we investigated whether BP extracts attenuated HFD-induced obesity in rats. Oral administration of BPE reduced HFD-induced body weight gain significantly without affecting food intake. The epididymal or perirenal adipose tissue weights were lower in rats on an HFD plus BPE compared with the tissue weights of HFD-induced obese rats. Total cholesterol and triglyceride levels in the rats fed BPE were modestly reduced, and the HDL-cholesterol level was significantly increased in HFD plus BP-fed rats compared with those of HFD-fed rats. Taken together, these results demonstrated an inhibitory effect of BP on adipogenesis through the down-regulation of C/EBPß, C/EBPα, and PPARγ and the reduction of the phospho-Akt adipogenic factor in 3T3-L1 cells. Moreover, BPE reduced body weight gain and inhibited fat accumulation in an HFD-induced animal model of obesity.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Mirtilos Azuis (Planta)/química , Frutas/química , Obesidade/tratamento farmacológico , Preparações de Plantas/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/genética , Animais , Peso Corporal/efeitos dos fármacos , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Dieta Hiperlipídica , Ingestão de Alimentos/efeitos dos fármacos , Regulação da Expressão Gênica , Masculino , Camundongos , Obesidade/metabolismo , Obesidade/fisiopatologia , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
BACKGROUND: Centipede grass (CG) originates from China and South America and is reported to contain several C-glycosyl flavones and phenolic constituents, including maysin and luteolin derivatives. This study aimed to investigate, for the first time, the antiobesity activity of CG and its potential molecular mechanism in 3T3-L1 cells. METHODS: To study the effect of CG on adipogenesis, differentiating 3T3-L1 cells were treated every day with CG at various concentrations (0-100 µg/ml) for six days. Oil-red O staining and triglyceride content assay were performed to determine the lipid accumulation in 3T3-L1 cells. The expression of mRNAs or proteins associated with adipogenesis was measured using RT-PCR and Western blotting analysis. We examined the effect of CG on level of phosphorylated Akt in 3T3-L1 cells treated with CG at various concentration s during adipocyte differentiation. RESULTS: Differentiation was investigated with an Oil-red O staining assay using CG-treated 3T3-L1 adipocytes. We found that CG suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells in a dose-dependent manner. Treatment of the 3T3-L1 adipocytes with CG resulted in an attenuation of the expression of adipogenesis-related factors and lipid metabolic genes. The expression of C/EBPα and PPARγ, the central transcriptional regulators of adipogenesis, was decreased by the treatment with CG. The expression of genes involved in lipid metabolism, aP2 were significantly inhibited following the CG treatment. Moreover, the CG treatment down-regulated the phosphorylation levels of Akt and GSK3ß. CONCLUSIONS: Taken collectively, these data indicated that CG exerts antiadipogenic activity by inhibiting the expression of C/EBPß, C/EBPα, and PPARγ and the Akt signaling pathway in 3T3-L1 adipocytes.
Assuntos
Adipogenia/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/antagonistas & inibidores , Expressão Gênica/efeitos dos fármacos , PPAR gama/antagonistas & inibidores , Extratos Vegetais/farmacologia , Poaceae , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Fármacos Antiobesidade/farmacologia , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Relação Dose-Resposta a Droga , Regulação para Baixo , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Flavonoides/farmacologia , Glucosídeos/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Luteolina/farmacologia , Camundongos , Fosforilação , Polifenóis/farmacologia , Transdução de SinaisRESUMO
Fraxinus rhynchophylla showed significant inhibitory activity on adipocyte differentiation in the 3T3-L1 preadipocyte cell line as assessed by measuring fat accumulation using Oil Red O staining. Further fractionation led to the isolation of two secoiridoids, oleuropein and hydroxyframoside B. Hydroxyframoside B significantly reduced fat accumulation and triglyceride content in differentiated 3T3-L1 cells without affecting cell viability, whereas oleuropein showed little effect. Further studies with interval treatment demonstrated that hydroxyframoside B exerted inhibitory activity on adipocyte differentiation when treated within 2 days (days 0-2) after differentiation induction. In addition, hydroxyframoside B significantly blocked the induction of adipogenic transcription factors such as C/EBP α, C/EBP ß, and PPAR γ. Taken together, these results suggest that hydroxyframoside B inhibited early/middle stage of adipogenic differentiation, in part, via inhibition of C/EBP α, C/EBP ß, and PPAR γ-dependent pathways.
Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Diferenciação Celular/efeitos dos fármacos , Fraxinus/química , Iridoides/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Avaliação Pré-Clínica de Medicamentos , Iridoides/química , Camundongos , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/metabolismoRESUMO
We previously showed that an ethanolic extract of the edible brown algae Petalonia binghamiae promotes the differentiation of 3T3-L1 preadipocytes and decreases hyperglycemia in streptozotocin-induced diabetic mice. Here, we report that a water-soluble extract of P. binghamiae thalli, prepared by enzymatic digestion, inhibits preadipocyte differentiation and adipogenesis in a dose-dependent manner. In differentiating 3T3-L1 preadipocytes, the extract (designated PBEE) decreased the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding proteins α and ß, and fatty acid-binding protein aP2. It also inhibited the mitotic clonal expansion process of adipocyte differentiation, and it inhibited insulin-stimulated uptake of glucose into mature 3T3-L1 adipocytes by reducing phosphorylation of insulin receptor substrate-1. In rats with high-fat diet (HFD)-induced obesity, PBEE exhibited potent anti-obesity effects. In this animal model, increases in body weight and fat storage were suppressed by the addition of PBEE to the drinking water at 500 mg/L for 30 days. PBEE supplementation reduced serum levels of glutamic pyruvic and glutamic oxaloacetic transaminases and increased the serum level of high-density lipoprotein cholesterol. Moreover, it significantly decreased the accumulation of lipid droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Taken together, these data demonstrate that PBEE inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.
Assuntos
Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Dieta , Phaeophyceae/química , Aumento de Peso/efeitos dos fármacos , Células 3T3-L1 , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal , Proteína alfa Estimuladora de Ligação a CCAAT/antagonistas & inibidores , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Gorduras na Dieta/metabolismo , Masculino , Camundongos , Obesidade/metabolismo , PPAR gama/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
p27SJ is a novel protein from a callus culture of St. John's wort that modulates transcription of the HIV-1 promoter in several mammalian cells [Darbinian-Sarkissian, N., Darbinyan, A., Otte, J., Radhakrishnan, S., Sawaya, B.E., Arzumanyan, A., Chipitsyna, G., Popov, Y., Rappaport, J., Amini, S., Khalili, K., 2006. p27(SJ), a novel protein from St. John's wort, that suppresses expression of HIV-1 genome. Gene Ther. 13, 288-295]. Here, we armed p27SJ with signals from Ig-kappa light chain that allow its efficient excretion from the cells, and from HIV-1 Tat that facilitates its uptake by other cells for its utilization by a protein transduction method. We demonstrate that treatment of cells containing the HIV-1 LTR with conditioned media from cells expressing the armed p27SJ ((exc)p27SJ(upt)) results in suppression of the viral activation by the C/EBPbeta transcription factor. Once imported into the cells, (exc)p27SJ(upt) impacts the nuclear localization of C/EBPbeta and by retaining the protein in the cytoplasm affects its DNA binding and hence transcriptional activity. The armed p27SJ also inhibits Tat-induced activation of the LTR and decreases the level of viral replication in promonocytic cells including U-937 and T-lymphocytic cells. Our observations introduce a new bi-directional protein transduction system with a broad spectrum of applications for manufacturing therapeutic peptides by a specific group of cells called donor, and delivery to the target cells named recipient. Furthermore, our results support the utility of soluble p27SJ in suppressing transcription and replication of HIV-1 by interfering with the function of cellular proteins such as C/EBPbeta and viral activators including Tat.
Assuntos
Fármacos Anti-HIV/metabolismo , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Hypericum/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Transcrição Gênica , Fármacos Anti-HIV/isolamento & purificação , Astrócitos/virologia , Proteína beta Intensificadora de Ligação a CCAAT/antagonistas & inibidores , Linhagem Celular , Células Cultivadas , Proteína do Núcleo p24 do HIV/biossíntese , Humanos , Microglia/virologia , Monócitos/virologia , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Linfócitos T/virologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/antagonistas & inibidoresRESUMO
Rehmannia glutinosa, a Traditional Chinese Medicine (TCM), has been used to increase physical strength. Here, we report that Rehmannia glutinosa extract (RE) inhibits adipocyte differentiation and adipogenesis. RE impairs differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. At the molecular level, treatment with RE inhibits expression of the key adipocyte differentiation regulator C/EBPbeta, as well as C/EBPalpha and the terminal marker protein 422/aP2, during differentiation of preadipocytes into adipocytes. Additionally, RE inhibits the mitotic clonal expansion (MCE) process of adipocyte differentiation, and RE prevents localization of C/EBPbeta to the centromeres. RE also prevents high fat diet (HFD) induced weight gain and adiposity in rats. Taken together, our results indicate that Rehmannia glutinosa extract inhibits preadipocyte differentiation and adipogenesis in cultured cells and in rodent models of obesity.