RESUMO
Resveratrol (RSV) is a natural polyphenol present in grapes, the skin of peanuts, and several other plants with many health benefits. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that may be linked to neural and synaptic development impairments. The present study aimed to analyze the preventive effects of RSV on the development of ASD-like behavior, using oxytocin receptor gene knockout (Oxtr-KO) and valproic acid-induced ASD (VPA-ASD) model mice. Genetic deficiencies in Oxtr are suggested to be involved in ASD etiology. Twenty-four hours after a single RSV injection to the Oxtr-KO mice, the social impairments caused by OXTR deficiency were ameliorated. RSV also improved social impairments in the VPA-ASD mice. Administration of RSV up-regulated silent information regulator 1 (Sirt1) gene and early growth response factor 3 (Egr3) gene expressions in the amygdala of the Oxtr-KO mice. Our data suggest that RSV may have therapeutic effects on ASD with multiple targets.
Assuntos
Transtorno do Espectro Autista/psicologia , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Comportamento Social , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Sirtuína 1/metabolismoRESUMO
Red wines are thought to be one of the major dietary sources of trans-resveratrol. The beneficial effects of t-resveratrol against metabolic disorders have been well characterized, however, red wines also contain various resveratrol derivatives whose health benefits have not been completely elucidated. In this report, we investigated ε-viniferin, a resveratrol dimer, which is present at comparable concentrations to t-resveratrol in red wines, and has higher anti-adipogenesis activity in 3T3-L1 cells. In addition, ε-viniferin was more effective than t-resveratrol in its anti-obesity and anti-inflammatory effects in high-fat diet fed mice. These results suggested ε-viniferin may be one of the active ingredients against metabolic disorders in red wines, in addition to t-resveratrol.
Assuntos
Adipogenia/efeitos dos fármacos , Benzofuranos/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Obesidade/prevenção & controle , Obesidade/fisiopatologia , Estilbenos/administração & dosagem , Células 3T3 , Animais , Fármacos Antiobesidade/administração & dosagem , Benzofuranos/química , Dimerização , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Resveratrol , Estilbenos/química , Resultado do TratamentoRESUMO
Resveratrol, a polyphenolic phytoalexin found in red wine and various plants, has been reported to up-regulate the expression of endothelial NO synthase (eNOS) in human umbilical vein endothelial cells (HUVEC). However, this effect was neither long term in nature nor physiologically relevant at the concentration of resveratrol studied. In the present study, we investigated the effects of repeated treatments with a lower concentration of resveratrol on the expression of genes in HUVEC. The expression levels of eNOS and silent mating type information regulation 2 homologue 1 (SIRT1) were up-regulated in HUVEC by repeated treatments with 1 µM-resveratrol for 6 d, but not with fenofibrate. Moreover, resveratrol treatment increased the expression of autophagy-regulated genes such as γ-aminobutyric acid A receptor-associated protein (GABARAP), microtubule-associated protein 1 light chain 3B (LC3B) and autophagy-related protein 3 (ATG3), the radical scavenger activity-related metallothionein-1X (MT1X) gene and the anti-inflammatory activity-related annexin A2 (ANXA) gene. In addition, resveratrol treatment down-regulated the expression of the cell-cycle checkpoint control RAD9 homologue B (RAD9B) gene. These results indicate the beneficial effects of resveratrol on the cardiovascular system.
Assuntos
Autofagia/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Extratos Vegetais/administração & dosagem , Sirtuína 1/metabolismo , Estilbenos/administração & dosagem , Autofagia/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Extratos Vegetais/farmacologia , Resveratrol , Estilbenos/farmacologia , Regulação para Cima , VinhoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disease that causes dry skin and functional disruption of the skin barrier. AD is often accompanied by allergic inflammation. AD patient suffer from heavy itching, and their quality of life is severely affected. Some pharmaceuticals for AD have some side effects such as skin atrophy. So it is necessary to develop mild solutions such as food ingredients without side effects. There are various causes of AD. It is especially induced by immunological imbalances such as IFN-γ reduction. IFN-γ has an important role in regulating IgE, which can cause an allergy reaction. NC/Nga mice develop AD and IgE hyperproduction. In a previous study, we revealed that administration of polysaccharide from black currant (R. nigrum) has an effect on immunomodulation. It induces IFN-γ production from myeloid dendritic cells. We named this polysaccharide cassis polysaccharide (CAPS). In this report, we studied the effect of administering CAPS on atopic dermatitis in NC/Nga mice. Thirty NC/Nga mice that developed symptoms of atopic dermatitis were used. We divided them into three groups (control, CAPS administration 12 mg/kg/day, CAPS administration 60 mg/kg/day). For 4 weeks, we evaluated clinical score, serum IgE levels, gene expression of spleen, and skin pathology. We revealed that CAPS administration improves atopic dermatitis symptoms. We also found that CAPS administration suppresses IgE hyperproduction and induces IFN-γ gene transcription in the spleen. Finally, we confirmed that CAPS administration suppresses mast cell migration to epidermal skin. These results indicated that CAPS has an effect on AD.
RESUMO
Blackcurrants (Ribes nigrum L.) have various benefits for human health. In particular, a polysaccharide derived from blackcurrant was found to be an immunostimulating food ingredient in a mouse model. We named a polysaccharide derived from blackcurrant cassis polysaccharide (CAPS). In a previous clinical study, we reported that CAPS affects skin dehydration, demonstrating its effectiveness against skin inflammation was related to atopic dermatitis; skin inflammation caused skin dehydration. However, there are no studies regarding CAPS effectiveness against skin dehydration. The current study aimed to investigate CAPS effectiveness against skin dehydration. We further demonstrate the effect of oral administration of CAPS on skin dehydration caused by ultraviolet (UV) irradiation-induced inflammation in mice. We found that CAPS administration suppresses skin dehydration caused by UV irradiation. We also found that CAPS decreases interleukin-6 and matrix metalloproteinase transcription levels in the mouse skin. These results show that CAPS improves skin hydration in UV-irradiated mice.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Dermatite Atópica/terapia , Carboidratos da Dieta/uso terapêutico , Frutas/química , Extratos Vegetais/uso terapêutico , Ribes/química , Pele/metabolismo , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Dermatite Atópica/etiologia , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/análise , Carboidratos da Dieta/isolamento & purificação , Fibras na Dieta/administração & dosagem , Fibras na Dieta/análise , Fibras na Dieta/uso terapêutico , Suplementos Nutricionais/análise , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 13 da Matriz/química , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Camundongos Pelados , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prebióticos/administração & dosagem , Prebióticos/análise , Lesões Experimentais por Radiação/imunologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/terapia , Pele/imunologia , Pele/efeitos da radiação , Organismos Livres de Patógenos Específicos , Raios Ultravioleta/efeitos adversos , Água/metabolismoRESUMO
We investigated the efficacy of the polysaccharide derived from black currant, named cassis polysaccharide (CAPS), for inhibiting Japanese cedar pollinosis symptoms and improving quality of life by a randomized double-blind, placebo-controlled trial in 2006. A total of 28 subjects were enrolled in the study, and 10 subjects in each group completed the trial. Although there was no significant difference between the CAPS and placebo group in the weekly mean value of any symptom in the daily symptom diary at any time, a smaller degree of final symptom aggravation was found in the CAPS group. Significant aggravation of the score was finally observed in the placebo group with inferior conch swelling and with sneezing, itchy nose, itchy eye and watery eye in the Japan rhino-conjunctivitis quality of life questionnaire assessment, while the changes observed in the CAPS group were not significant. In conclusion, our findings clearly indicate that CAPS would be useful as a food supplement in assisting the treatment of Japanese cedar pollinosis.
Assuntos
Antialérgicos/farmacologia , Cryptomeria/imunologia , Polissacarídeos/farmacologia , Rinite Alérgica Sazonal/tratamento farmacológico , Ribes/química , Adulto , Idoso , Alérgenos/imunologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólen/imunologiaRESUMO
Black currant (Ribes nigrum) has various beneficial properties for human health. In particular, polysaccharide from black currant was found to be an immunostimulating food ingredient and was reported to have antitumor activity in a mouse model. We named it cassis polysaccharide (CAPS). In a previous study, CAPS administration caused tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) production in vitro and in vivo, but the immunological mechanism of CAPS was not demonstrated. In this study, we revealed the CAPS immunostimulating mechanism in vitro. First, we found that CAPS activated dendritic cells (DCs). Second, we investigated whether it depends on Toll-like receptor 4 (TLR4) and myeloid differentiation primary response (Myd). We concluded that CAPS stimulates DCs through Myd88 depending TLR4 signaling and activates Th1-type cytokine release.
RESUMO
Both caloric restriction (CR) and resveratrol (RSV) have beneficial effects on obesity. However, the biochemical pathways that mediate these beneficial effects might be complex and interconnected and have not been fully elucidated. To reveal the common therapeutic mechanism of CR and RSV, we performed a comparative transcriptome analysis of adipose tissues from diet-induced obese (DIO) zebrafish and obese humans. We identified nine genes in DIO zebrafish and seven genes in obese humans whose expressions were regulated by CR and RSV. Although the gene lists did not overlap except for one gene, the gene ontologies enriched in the gene lists were highly overlapped, and included genes involved in adipocyte differentiation, lipid storage and lipid metabolism. Bioinformatic analysis of cis-regulatory sequences of these genes revealed that their transcriptional regulators also overlapped, including EP300, HDAC2, CEBPB, CEBPD, FOXA1, and FOXA2. We also identified 15 and 46 genes that were dysregulated in the adipose tissue of DIO zebrafish and obese humans, respectively. Bioinformatics analysis identified EP300, HDAC2, and CEBPB as common transcriptional regulators for these genes. EP300 is a histone and lysyl acetyltransferase that modulates the function of histone and various proteins including CEBPB, CEBPD, FOXA1, and FOXA2. We demonstrated that adiposity in larval zebrafish was significantly reduced by C646, an inhibitor of EP300 that antagonizes acetyl-CoA. The reduction of adiposity by C646 was not significantly different from that induced by RSV or co-treatment of C646 and RSV. These results indicate that the inhibition of EP300 might be a common therapeutic mechanism between CR and RSV in adipose tissues of obese individuals.
RESUMO
A polysaccharide-rich substance isolated from black currant, named cassis polysaccharide (CAPS), was partially digested with beta-galactosidase from Aspergillus oryzae and its immunostimulatory activity was investigated. The in vitro cytokine-inducing effect of CAPS on RAW264 cells was gradually decreased along with lowering of the average MW of CAPS. In vivo, partially digested CAPS with a mean MW of approximately 20,000 showed the most potent antitumor activity against Ehrlich carcinoma in mice.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Polissacarídeos/metabolismo , Polissacarídeos/farmacologia , Ribes/química , beta-Galactosidase/farmacologia , Animais , Antineoplásicos/química , Aspergillus oryzae/enzimologia , Soluções Tampão , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Peso Molecular , Transplante de Neoplasias , Fosfatos/química , Polissacarídeos/química , Padrões de Referência , Temperatura , Fatores de Tempo , Transplante HomólogoRESUMO
The fruit juice of black currant was found to contain a polysaccharide-rich substance, which was designated cassis polysaccharide (CAPS), with macrophage-stimulating activity. Especially, its interleukin (IL)-1beta-inducing activity was remarkably high, compared with other fruit juice preparations. CAPS was found to consist of rhamnose, mannose, arabinose, galactose, xylose, and glucose in a molar ratio of 11.3:0.9:54.1:29.8:2.0:1.9. CAPS turned out to be partitioned into a soluble component (CAPS-l.m.) and a precipitable component (CAPS-h.m.) with mean MWs of 80,000 and 600,000 respectively in 45% (v/v) ethanol solution. At least in vitro, CAPS-l.m. rather than CAPS-h.m. appeared to play an important role in macrophage activation. Oral administration of black currant juice and CAPS to Ehrlich carcinoma-bearing mice retarded the growth of the solid tumor by 45% and 51% respectively. CAPS administration had a stimulatory effect on the release of IL-2, IL-10, interferon-gamma, and IL-4 from splenocytes in comparison with PBS treatment in tumor-bearing mice. The IL-4 level was, however, still lower than that exhibited by a group of normal mice. CAPS showed a certain cytotoxicity directly against tumor cells.
Assuntos
Antineoplásicos/farmacologia , Imunidade/efeitos dos fármacos , Polissacarídeos/farmacologia , Ribes/química , Animais , Antineoplásicos/isolamento & purificação , Carboidratos/análise , Carcinoma de Ehrlich/tratamento farmacológico , Feminino , Interferon gama/metabolismo , Interleucinas/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Solubilidade , Baço/citologia , Baço/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
Two peptides that inhibit prolyl endopeptidase were isolated from a red wine made from Cabernet Sauvignon grapes. Their amino acid sequences and IC50 values were Val-Glu-Ile-Pro-Glu (17.0 microM) and Tyr-Pro-Ile-Pro-Phe (87.8 microM). The peptides also suppressed the degradation levels of the bioactive peptides vasopressin, substance P, and neurotensin fragments 8-13, which are involved in memory and neural communication.