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1.
An Acad Bras Cienc ; 91(3): e20181330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508665

RESUMO

Type 1 diabetes (T1D) is the result of the selective destruction of the pancreatic ß-cells by T cells of the immune system. Although spleen is a secondary lymphoid organ, it is also involved in the T1D pathogenesis. However, the alterations in a variety of cellular processes of this disease need to be further understood. We aimed to analyze the benefits of resveratrol, and its complexed form on diabetic complications in the spleen of rats. To this end, we investigated important enzymes of phosphoryl transfer network, and Na+, K+-ATPase activity. Wistar rats were divided into non-diabetic groups: Control, Ethanol, Resveratrol, Hydroxypropyl-ß-cyclodextrin, Resveratrol-hydroxypropyl-ß-cyclodextrin, and diabetic groups with the same treatments. Diabetes was induced by a single dose of 60 mg/kg of streptozocin intraperitoneally, and treatments by intragastric gavage once daily for 60 days. Hyperglycemia reduced creatine kinase activity, which was reversed by the administration of resveratrol. Na+, K+-ATPase activity was greatly affected, but it was reversed by resveratrol and resveratrol-hydroxypropyl-ß-cyclodextrin. This suggest an energetic imbalance in the spleen of diabetic rats, and in case this also occurs in the diabetic patients, it is possible that resveratrol supplementation could be beneficial to the better functioning of the spleen in diabetic patients.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Resveratrol/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Baço/metabolismo , Animais , Antioxidantes/metabolismo , Glicemia/análise , Peso Corporal , Creatina Quinase/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Metabolismo Energético/efeitos dos fármacos , Hiperglicemia/metabolismo , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Estreptozocina
2.
Acta Cir Bras ; 34(7): e201900704, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531539

RESUMO

PURPOSE: The effects of resveratrol administration on calvarial bone defects with alloplastic graft material was investigated for osteoinductive reaction and bone development in rats. METHODS: Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows: control (defect) group, defect + graft group, and defect + graft + resveratrol group. A calvarial bone defect was created in all groups, alloplastic bone grafts were applied to the defect in the 2nd and 3rd group, resveratrol (5 mg/kg/day) was added to the drinking water of the animals following graft application for 28 days in the 3rd group. RESULTS: Increase in osteoclasts and necrotic changes were observed histopathologically in the control group. In the 2nd group, reduction of inflammation, congestion of blood vessels, increased osteblastic activity, osteoinductive effect, progression of osteocyte development and increased collagen fibers in connective tissue were observed. In the 3rd group, osteoblasts seemed to secrete bone matrix and accelerate osteoinductive effect with increased osteopregenitor activity and positive osteopontin and osteonectin expressions. CONCLUSION: Resveratrol treatment was thought to be an alternative and supportive drug for implant application by inducing new bone formation in the calvaral defect region as a result of short-term treatment.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Transplante Ósseo/métodos , Resveratrol/administração & dosagem , Crânio/cirurgia , Animais , Substitutos Ósseos/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Masculino , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteonectina/administração & dosagem , Osteopontina/administração & dosagem , Ratos , Crânio/efeitos dos fármacos
3.
Shanghai Kou Qiang Yi Xue ; 28(3): 237-240, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489408

RESUMO

PURPOSE: To investigate the protective effect and mechanism of resveratrol on oxidative stress of MC3T3-E1. METHODS: The levels of reactive oxygen species in the cells were observed by fluorescence microscope and flow cytometry. The expression of SOCS-1 protein was detected by Western blot. SOCS-1 transient transfected cell line was established, and the levels of reactive oxygen species in transfected cells were observed by fluorescence microscopy and flow cytometry. The data were analyzed using SPSS22.0 software package. RESULTS: The level of ROS in LPS group was significantly higher than that in the blank group and LPS+RES group (P<0.05). The expression level of SOCS-1 protein was increased after LPS stimulation for 30 min (P<0.05). The level of ROS in the siSOCS-1+LPS+RES group was significantly higher than that in the untransfected group (P<0.05). CONCLUSIONS: Resveratrol may counteract LPS-mediated oxidative stress in MC3T3E1 cells by modulating SOCS-1 protein.


Assuntos
Estresse Oxidativo , Resveratrol , Estilbenos , Proteínas Supressoras da Sinalização de Citocina , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Resveratrol/farmacologia , Proteínas Supressoras da Sinalização de Citocina/metabolismo
4.
Int J Nanomedicine ; 14: 6061-6071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534336

RESUMO

Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, is clinically employed to treat cancers especially for breast cancer and lung cancer. But its clinical applications are limited by the dose-dependent cardiac toxicity. Resveratrol (Res), a polyphenolic antitoxin, has been proved to be capable of improving the cardiomyocyte calcium cycling by up-regulating SIRT-1-mediated deacetylation to inhibit DOX-induced cardiotoxicity. Purpose: The objective of this study was to develop a solid lipid nanoparticle (SLN) loaded with Res to trigger inhibition of DOX-induced cardiotoxicity. Methods: Res-SLN was prepared by emulsification-diffusion method followed by sonication and optimized using central composite design/response surface method. The Res-SLN was further evaluated by dynamic light scattering, transmission electron microscopy for morphology and high performance liquid chromatography for drug loading and release profile. And the Res distribution in vivo was determined on rats while the effect of inhibit DOX-induced cardiotoxicity was investigated on mice. Results: Res-SLN with homogeneous particle size of 271.13 nm was successfully formulated and optimized. The prepared Res-SLN showed stable under storage and sustained release profile, improving the poor solubility of Res. Heart rate, ejection fractions and fractional shortening of Res-SLN treating mice were found higher than those on mice with cardiac toxicity induced by single high-dose intraperitoneal injection of DOX. And the degree of myocardial ultrastructural lesions on mice was also observed. Conclusion: Res-SLN has a certain therapeutic effect for protecting the myocardium and reducing DOX-induced cardiotoxicity in mice.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/efeitos adversos , Lipídeos/química , Nanopartículas/química , Resveratrol/uso terapêutico , Animais , Cardiotoxicidade/patologia , Feminino , Humanos , Masculino , Camundongos , Miocárdio/patologia , Nanopartículas/ultraestrutura , Ratos Sprague-Dawley , Resveratrol/química , Resveratrol/farmacocinética , Resveratrol/farmacologia
5.
J Agric Food Chem ; 67(42): 11752-11757, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31554403

RESUMO

Resveratrol (3,5,4'-trihydroxystilbene) is one of the most abundant polyphenols in red grapes, and red wine represents one of the most important dietary sources of this compound. Although its beneficial properties on human health have been widely investigated over the last 30 years, very little is known about its derivatives. Resveratrol can indeed undergo glycosylation, oligomerization and, upon UV-light exposure, it can isomerize from the trans-to the cis-isomer, which can further cyclize to 2,4,6-trihydroxyphenanthrene (THP). Although the effects of THP on human health are not yet known, being a polycyclic aromatic hydrocarbon, it can be potentially harmful. Because no data about THP occurrence in plant food and beverages are available, a simple procedure based on liquid-liquid extraction and gas chromatography-mass spectrometry has been developed and validated for the simultaneous qualitative and quantitative analysis of trans-resveratrol, cis-resveratrol, and THP in red wine, before and after UV-light exposure.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Fenantrenos/química , Resveratrol/química , Vinho/análise , Vinho/efeitos da radiação , Glicosilação , Isomerismo , Raios Ultravioleta
6.
Biol Res ; 52(1): 45, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426853

RESUMO

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.


Assuntos
Apoptose/efeitos dos fármacos , Artrite Experimental/fisiopatologia , Canais de Cálcio/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Proteína ORAI1/efeitos dos fármacos , Resveratrol/farmacologia , Molécula 1 de Interação Estromal/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Animais , Canais de Cálcio/fisiologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Resveratrol/administração & dosagem
7.
Life Sci ; 233: 116748, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412263

RESUMO

AIMS: Resveratrol is a polyphenolic compound that has received much attention for its use in ameliorating various systemic pathological conditions. The present study was performed to investigate whether the resveratrol alleviated cardiac hypertrophy and functional remodelling by regulating autophagy. MATERIALS AND METHODS: Male rats were exposed to CIH 8 h/day for five weeks and/or intragastric administration of resveratrol daily. The morphological and echocardiography were used to evaluate the cardiac protective effects. The apoptosis was detected by TUNEL staining. The biochemical assessments were used to evaluate oxidative stress. Further, the effect of resveratrol on autophagy and PI3K/AKT/mTOR pathway was investigated. KEY FINDINGS: The CIH group exhibited increased heart weight/body weight and left ventricle weight/body weight ratios, which was accompanied by left ventricular remodelling. Echocardiography analysis showed that CIH-treated rats had significantly higher left ventricular posterior wall thickness, ejection fraction and fractional shortening than those of controls. In addition, the apoptosis index and oxidative markers were significantly elevated in the CIH group versus the control. The autophagy marker Beclin-1 was elevated, while p62 was decreased by CIH treatment. Resveratrol treatment significantly improved cardiac function and alleviated cardiac hypertrophy, oxidative stress, and apoptosis in CIH rats. Further results indicated that PI3K/AKT pathway-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway played a role in the activation of autophagy by resveratrol after CIH stimulation. SIGNIFICANCE: In conclusion, resveratrol supplementation during CIH upregulates autophagy by targeting the PI3K/AKT/mTOR pathway, which appears to be beneficial for resisting cardiac hypertrophy.


Assuntos
Cardiomegalia/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia/complicações , Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Resveratrol/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Antioxidantes/farmacologia , Apoptose , Autofagia , Cardiomegalia/etiologia , Cardiomegalia/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
8.
Int J Nanomedicine ; 14: 4413-4428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417252

RESUMO

Background: As part of our continuing quest to enhance the efficacy of bioactive phytochemicals in cancer therapy, we report an innovative green nanotechnology approach toward the use of resveratrol for the production of biocompatible resveratrol-conjugated gold nanoparticles (Res-AuNPs). Our overarching aim is to exploit the inherent pro-apoptotic properties of gold nanoparticles (AuNPs) through synergistic anti-tumor characteristics of resveratrol, with the aim of developing a new class of green nanotechnology-based phytochemical-embedded AuNPs for applications in oncology. Method: Resveratrol was used to reduce Au3+ to Au0 for the synthesis of Res-AuNPs at room temperature and gum arabic (GA) was used to further encapsulate the nanoparticulate surface to increase the overall stability of the AuNPs. This comprehensive study involves the synthesis, full characterization and in vitro stability of Res-AuNPs in various biological media for their ultimate applications as anti-cancer agents against human breast (MDAMB-231), pancreatic (PANC-1) and prostate (PC-3) cancers. Results: This strategy to systematically increase the corona of resveratrol on AuNPs, in order to gain insights into the interrelationship of the phytochemical corona on the overall anti-tumor activities of Res-AuNPs, proved successful. The increased resveratrol corona on Res-AuNPs showed superior anti-cancer effects, attributed to an optimal cellular uptake after 24-hour incubation, while GA provided a protein matrix support for enhanced trans-resveratrol loading onto the surface of the AuNPs. Conclusion: The approach described in this study harnesses the benefits of nutraceuticals and nanoparticles toward the development of Res-AuNPs. We provide compelling evidence that the increased corona of resveratrol on AuNPs enhances the bioavailability of resveratrol so that therapeutically active species can be optimally available in vivo for applications in cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/patologia , Ouro/química , Nanopartículas Metálicas/química , Neoplasias Pancreáticas/patologia , Neoplasias da Próstata/patologia , Resveratrol/farmacologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endocitose , Feminino , Humanos , Concentração Inibidora 50 , Masculino , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Polifenóis/química , Polifenóis/farmacologia , Resveratrol/química , Espectrofotometria Ultravioleta , Resultado do Tratamento
9.
Int J Nanomedicine ; 14: 5215-5228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371957

RESUMO

Background: Resveratrol (RSV) has attracted interest as an alternative drug for the treatment of acute lung injury (ALI) and other pulmonary diseases, but its poor oral bioavailability is a limitation. In this study, we employed drug delivery nanotechnology to improve the stability, lung localization and efficacy of orally administered resveratrol to control lung damage leading to ALI. Methods and materials: RSV-loaded lipid-core nanocapsules (RSV-LNCs), prepared by interfacial deposition of biodegradable polymers, were given orally to A/J mice prior to lipopolysaccharide (LPS) intranasal instillation. Inflammatory changes, oxidative stress and lung tissue elastance were assessed 24 h after LPS challenge. Results: RSV-LNCs (5 mg/kg), given 1, 4, 6 or 12 h but not 24 h before provocation, inhibited LPS-induced leukocyte accumulation in the bronchoalveolar fluid (BALF), whereas unloaded nanocapsules (ULNCs) or free RSV (5 mg/kg) were ineffective. RSV-LNCs (2.5-10 mg/kg) but not ULNCs or RSV improved lung function and prevented total leukocyte and neutrophil accumulation equally in both BALF and lung tissue when given 4 h before LPS challenge. Similar findings were seen concerning the generation of a range of pro-inflammatory cytokines such as IL-6, KC, MIP-1α, MIP-2, MCP-1 and RANTES in lung tissue. In addition, only RSV-LNCs inhibited MDA levels and SOD activity in parallel with blockade of the ERK and PI3K/Akt pathways following LPS provocation. Conclusion: Nanoformulation of RSV in biodegradable oil-core polymers is an effective strategy to improve the anti-ALI activity of RSV, suggesting that the modified-release formulation of this plant polyphenol may be of great value in clinical conditions associated with ALI and respiratory failure.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Nanocápsulas/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/administração & dosagem , Resveratrol/uso terapêutico , Transdução de Sinais , Lesão Pulmonar Aguda/complicações , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Hipersensibilidade Respiratória/complicações , Hipersensibilidade Respiratória/patologia , Resveratrol/farmacologia
10.
Shanghai Kou Qiang Yi Xue ; 28(2): 128-132, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31384895

RESUMO

PURPOSE: To investigate the effect of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) on the expression of macrophage inflammatory protein-2 (MIP-2) mRNA and protein levels in MC3T3-E1 cells and the influence of resveratrol on the expression of MIP-2 protein in P.e-LPS induced cells. METHODS: MC3T3-E1 cells were treated with different concentrations of P.e-LPS(0-50 mg/L) and 20 mg/L P.e-LPS for different time (0-48 h). The expression of MIP-2 mRNA and protein was detected by real-time RT-PCR and enzyme linked immunosorbent assay (ELISA). MC3T3-E1 cells were pretreated with resveratrol for 1 h in the presence of 20 mg/L P.e-LPS for 24 h,which was detected by ELISA. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: Treatment of MC3T3-El cells with different concentrations of P.e-LPS(0-50 mg/L) caused a significantly increase in MIP-2 mRNA and protein expression in dose-dependent manners.The expression of MIP-2 protein increased from (41.86±2.49) ng/L to (3126.74±158.30) ng/L, and the difference was significant(P<0.05). In the observation time (0-48 h), the impact of 20 mg/L P.e-LPS on induction of MIP-2 in MC3T3-El cells exhibited a time-dependent manner. At 48 h, the maximal induction of MIP-2 protein expression was (2102.55±123.27) ng/L(P<0.01). Incubation of cells with 10 µmol/L resveratrol for 1h significantly decreased the expression of MIP-2 protein from (1805.33±67.54) ng/L to(813.82±47.21) ng/L, and the difference was significant(P<0.05). CONCLUSIONS: The results suggest that P.e-LPS may mediate MIP-2 expression in MC3T3-E1 cells, and resveratrol has a significant inhibitory effect on this process.


Assuntos
Quimiocina CXCL2 , Lipopolissacarídeos , Osteoblastos , Resveratrol , Animais , Quimiocina CXCL2/efeitos dos fármacos , Quimiocina CXCL2/metabolismo , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Porphyromonas endodontalis , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Resveratrol/farmacologia
11.
AAPS PharmSciTech ; 20(6): 250, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297635

RESUMO

Melanoma is regarded as the fifth and sixth most common cancer in men and women, respectively, and it is estimated that one person dies from melanoma every hour in the USA. Unfortunately, the treatment of melanoma is difficult because of its aggressive metastasis and resistance to treatment. The treatment of melanoma continues to be a challenging issue due to the limitations of available treatments such as a low response rate, severe adverse reactions, and significant toxicity. Natural polyphenols have attracted considerable attention from the scientific community due to their chemopreventive and chemotherapeutic efficacy. It has been suggested that poorly soluble polyphenols such as curcumin, resveratrol, quercetin, coumarin, and epigallocatechin-3-gallate may have significant benefits in the treatment of melanoma due to their antioxidant, anti-inflammatory, antiproliferative, and chemoprotective efficacies. The major obstacles for the use of polyphenolic compounds are low stability and poor bioavailability. Numerous nanoformulations, including solid lipid nanoparticles, polymeric nanoparticles, micelles, and liposomes, have been formulated to enhance the bioavailability and stability, as well as the therapeutic efficacy of polyphenols. This review will provide an overview of poorly soluble polyphenols that have been reported to have antimetastatic efficacy in melanomas.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Melanoma/tratamento farmacológico , Polifenóis/administração & dosagem , Polifenóis/química , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/metabolismo , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/análogos & derivados , Catequina/química , Catequina/metabolismo , Curcumina/administração & dosagem , Curcumina/química , Curcumina/metabolismo , Humanos , Melanoma/metabolismo , Melanoma/prevenção & controle , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/metabolismo , Polifenóis/metabolismo , Quercetina/administração & dosagem , Quercetina/química , Quercetina/metabolismo , Resveratrol/administração & dosagem , Resveratrol/química , Resveratrol/metabolismo , Neoplasias Cutâneas/metabolismo , Solubilidade
12.
Chem Biodivers ; 16(8): e1900218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282123

RESUMO

Croatian wines made from native (Plavac mali and Teran) and non-native grape varieties (Cabernet Sauvignon and Merlot), all grown in Croatian coastal regions, were investigated. Analyses included measurements of antioxidant activities, total phenolic contents and concentrations of non-colored phenolic compounds, chosen based on their known nutraceutical properties. Plavac mali wines were distinguished by higher antioxidant activity, total phenolic content and catechin concentrations but lower flavonol concentrations. Teran wines had higher hydroxytyrosol, myricetin and resveratrol concentrations. Merlot and Cabernet Sauvignon wines had higher flavonol concentrations (except myricetin). Canonical analysis was successful in discriminating Plavac mali from Teran wines, and both varieties were separated from non-native varieties. The results indicate distinct genetic potentials of studied varieties and enable wine authentication based on the investigated bioactive compounds.


Assuntos
Fenóis/análise , Vitis/química , Vinho/análise , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Croácia , Análise Discriminante , Flavonoides/análise , Resveratrol/análise , Vitis/metabolismo
13.
Ecotoxicol Environ Saf ; 182: 109425, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31295660

RESUMO

BACKGROUND: Inhalation of fine particulate matter (PM2.5) induces the occurrence of lung inflammation and fibrosis, but its molecular mechanism remains unclear. Resveratrol (RES) is known to have anti-inflammatory properties in many pulmonary diseases. Here, we aimed to investigate the effect of long-term "real-world" ambient PM exposure on lung inflammation and fibrosis and further explore the protective effect and mechanism of RES. METHODS AND RESULTS: RES (50 and 100 mg/kg.bw) was administered to C57BL/6J mice that were exposed to ambient PM for 5 months. The control group breathed filtered air without RES, and the PM group was exposed to PM without RES. The inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and lung fibrosis were evaluated by enzyme-linked immune sorbent assay (ELISA) kits and Masson's trichrome staining. The real-time PCR and Western blot analysis were used to determine the signal pathway. In vivo, PM exposure markedly elevated the levels of inflammatory cytokines and TGF-ß1 in BALF, induced lung fibrosis. Meanwhile, PM exposure triggered autophagy process and activated the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in lung. Also, RES treatment abolished PM-induced lung inflammation and fibrosis, and inhibited autophagic process and NLRP3 inflammasome activation. In vitro, PM2.5-induced cytotoxicity in BEAS-2B cells dose-dependently. Besides, RES alleviated PM2.5-induced cytotoxicity, inhibited autophagic process and NLRP3 inflammasome activity and decreased IL-1ß production in BEAS-2B cells. CONCLUSION: Long-term PM exposure induced lung inflammation and fibrosis, and RES intervention alleviated these adverse effects via inhibiting autophagy-related NLRP3 inflammasome activation.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fibrose/tratamento farmacológico , Material Particulado/toxicidade , Pneumonia/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Citocinas/metabolismo , Inibidores Enzimáticos/uso terapêutico , Inflamassomos/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia/induzido quimicamente , Proteínas , Fibrose Pulmonar , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1
14.
J Agric Food Chem ; 67(31): 8510-8519, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31294559

RESUMO

Acrylamide, mainly formed in Maillard browning reaction during food processing, causes defects in liver circadian clock and mitochondrial function by inducing oxidative stress. Resveratrol is a polyphenol that has powerful antioxidant and anti-inflammatory activity. However, the preventive effects of resveratrol on acrylamide-triggered oxidative damage and circadian rhythm disorders are unclear at the current stage. The present research revealed that resveratrol pretreatment prevented acrylamide-induced cell death, mitochondrial dysfunction, and inflammatory responses in HepG2 liver cells. Acrylamide significantly triggered disorders of circadian genes transcription and protein expressions including Bmal1 and Cry 1 in primary hepatocytes, which were prevented by resveratrol pretreatment. Moreover, we found that the beneficial effects of resveratrol on stimulating Nrf2/NQO-1 pathway and mitochondrial respiration complex expressions in acrylamide-treated cells were Bmal1-dependent. Similarly, the inhibitory effects of resveratrol on inflammation signaling NF-κB were Cry1-dependent. In conclusion, these results demonstrated resveratrol could be a promising compound in suppressing acrylamide-induced hepatotoxicity and balancing the circadian clock.


Assuntos
Fatores de Transcrição ARNTL/imunologia , Acrilamida/toxicidade , Transtornos Cronobiológicos/imunologia , Criptocromos/imunologia , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Resveratrol/farmacologia , Fatores de Transcrição ARNTL/genética , Animais , Transtornos Cronobiológicos/tratamento farmacológico , Transtornos Cronobiológicos/genética , Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano/efeitos dos fármacos , Criptocromos/genética , Células Hep G2 , Hepatócitos/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/genética , Mitocôndrias/imunologia
15.
High Blood Press Cardiovasc Prev ; 26(4): 305-319, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31264084

RESUMO

INTRODUCTION: There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome (MetS); however, the findings are controversial. AIM: This systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders. METHODS: We searched systematically online databases including: PubMed-Medline, Embase, ISI Web of Science and Cochrane Central Register of Controlled Trials until October, 2018. Two independent authors extracted data and assessed the quality of included articles. Data were pooled using the fixed- or random-effects model and considered as standardized mean difference (SMD) with 95% confidence intervals (95% CI). RESULTS: Out of 831 electronic citations, 28 RCTs (with 33 findings reported) were included in the meta-analyses. The findings showed that resveratrol intervention significantly increased flow-mediated dilatation (FMD) levels (SMD 1.77; 95% CI 0.25, 3.29; P = 0.02; I2: 96.5). However, resveratrol supplements did not affect systolic blood pressure (SBP) (SMD - 0.27; 95% CI - 0.57, 0.03; P = 0.07; I2: 88.9) and diastolic blood pressure (DBP) (SMD - 0.21; 95% CI - 0.52, 0.11; P = 0.19; I2: 89.8). CONCLUSIONS: Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders, but did not affect SBP and DBP. Additional prospective studies are needed to investigate the effect of resveratrol supplementation on endothelial function and blood pressures, using higher-dose of resveratrol with longer durations.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Resveratrol/uso terapêutico , Vasodilatação/efeitos dos fármacos , Vasodilatadores/uso terapêutico , Adulto , Idoso , Suplementos Nutricionais/efeitos adversos , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Resveratrol/efeitos adversos , Resultado do Tratamento , Vasodilatadores/efeitos adversos
16.
Adv Exp Med Biol ; 1140: 665-684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347078

RESUMO

Stilbenes represent a class of compounds with a common 1,2-diphenylethylene backbone that have shown extraordinary potential in the biomedical field. As the most well-known example, resveratrol proved to have anti-aging effects and significant potential in the fight against cardiovascular diseases and some types of cancer. Mass spectrometry is an analytical method of critical importance in all studies related to stilbenes that are important in the biomedical field. From the discovery of new natural compounds and mapping the grape metabolome up to advanced investigations of stilbenes' potential for the protection of human health in clinical studies, mass spectrometry has provided critical analytical information. In this review we focus on various approaches related to mass spectrometry for the detection of stilbenes-such as coupling with chromatographic separation methods and direct infusion-with presentation of some illustrative applications. Clearly, the potential of mass spectrometry for assisting in the discovery of new stilbenes of biomedical importance, elucidating their mechanisms of action and quantifying minute quantities in complex matrices is far from being exhausted.


Assuntos
Espectrometria de Massas , Estilbenos/análise , Vinho/análise , Humanos , Resveratrol
17.
Anticancer Res ; 39(7): 3745-3755, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262901

RESUMO

BACKGROUND/AIM: The study is directed to the effect of resveratrol on the redox-status and viability of leukemic and normal lymphocytes, as well as its ability to sensitize leukemic lymphocytes to anticancer drugs. MATERIALS AND METHODS: Cytotoxicity was analyzed by trypan blue staining, apoptosis - by Annexin V test, and oxidative stress - by the intracellular levels of reactive oxygen species (ROS) and protein-carbonyl products. RESULTS: Incubation of resveratrol in combination with the majority of anticancer drugs resulted in higher toxicity than resveratrol or drug alone. In the case of leukemic lymphocytes treated with barasertib and everolimus in the presence of resveratrol, synergistic cytotoxicity was accompanied by strong induction of apoptosis, increased levels of hydroperoxides and insignificant changes in protein-carbonyl products. None of these parameters changed in normal lymphocytes. CONCLUSION: Resveratrol is a promising supplementary compound for anticancer therapy, that may allow reduction of the therapeutic doses of barasertib and everolimus, minimizing their side-effects.


Assuntos
Antineoplásicos/farmacologia , Leucemia/metabolismo , Linfócitos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Leucemia/tratamento farmacológico , Linfócitos/metabolismo , Oxirredução
18.
Phys Chem Chem Phys ; 21(29): 16190-16197, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31298243

RESUMO

Over the past few years, the interest in Resveratrol (3,4',5,-trihydroxystilbene, RSV) has increased due to the evidence found of its antioxidant action that protects biomolecules and cells from oxidative damage. The interest has been further exacerbated by the natural presence of RSV in some fruits and derivatives, especially in red wine. In this paper we present evidence of RSV capacity in protecting a deoxynucleotide, an essential constituent of DNA, from one-electron oxidation. This article evaluates the mechanism responsible for the antioxidant action of RSV, after one-electron oxidation of 2'-deoxyguanosine 5'-monophosphate (dGMP), by kinetic analysis during steady-state irradiation and laser flash photolysis experiments. Results showed that RSV protects dGMP by recovering the nucleotide from its radical, which is formed after the reaction of dGMP with the triplet excited state of the photosensitizer. In the absence of RSV, dGMP is irremediably oxidized, and if the damage occurs in dGMP located in DNA molecules, the consequences can be as serious as mutations and subsequent carcinogenic lesions.


Assuntos
Guanina/química , Resveratrol/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Elétrons , Neoplasias/prevenção & controle , Oxirredução/efeitos dos fármacos , Resveratrol/química
19.
Life Sci ; 232: 116607, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254582

RESUMO

AIMS: Poisoning with aluminium phosphide (AlP) commonly has a high rate of mortality and morbidities. Phosphine gas is the main cause of AlP poisoning that has deleterious effect on multi-organs especially heart, kidney, and liver. Furthermore, several studies reported that resveratrol has cytoprotective effects through its pleiotropic property. The purpose of this study was to estimate the dose-dependent role of resveratrol on phosphine induced acute hepatic toxicity in rat model. MAIN METHODS: The rats have been exposed to LD50 of AlP (12 mg/kg) by gavage, and resveratrol doses (20, 40, and 80 mg/kg) were injected 30 min after intoxication. After 24 h, the serum and liver tissue were collected for present study. KEY FINDINGS: The results indicated that phosphine causes an alteration in oxidative stress markers including elevation of ROS, and GSH level, MPO activity, reduction in SOD, catalase and G6PD activity as well as reduction in SOD1 and catalase expression. Furthermore, phosphine significantly induced phosphorylation of IkappaB, NF-kappaB and up-regulation of TNF-α, IL-1ß, IL-6, and ICAM-1 expression. Also, phosphine induces markedly reduced hepatocytes lives cell and elevated apoptosis and necrosis. Co-treatment of resveratrol in a dose-dependent manner reversed aforementioned alterations. All in all, histological analysis indicated a deleterious effect of phosphine on the liver, which is mitigated by resveratrol administration. SIGNIFICANCE: The results of the present study suggest targeting ROS/NF-kappaB signalling pathway by resveratrol may have a significant effect on the improvement of hepatic injury induced by phosphine. It also may be a possible candidate for the treatment of phosphine-poisoning.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/fisiologia , Fosfinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , NF-kappa B/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Ratos , Ratos Wistar , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
20.
Gen Physiol Biophys ; 38(3): 215-225, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31184308

RESUMO

The purpose of the study is to examine the protective effect of resveratrol on the fatty acid synthase gene expression against the side-effects of risperidone in an experimental model in rat liver. In this study, thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, RIS (2 mg/kg risperidone daily), RSV1 (2 mg/kg risperidone + 20 mg/kg resveratrol), RSV2 (2 mg/kg risperidone + 40 mg/kg resveratrol), and RSV3 group (2 mg/kg risperidone + 80 mg/kg resveratrol). On treatment day 15, liver tissue was taken for analysis. The resveratrol treatment significantly reduced weight gain as opposed to the risperidone administration. Moreover, the fatty acid synthase gene expression level increased significantly in RSV1 group (p = 0.011). In addition, resveratrol enhanced the total antioxidant status, high-density lipoprotein cholesterol levels and decreased alanine aminotransferase, aspartate aminotransferase, total cholesterol, gamma glutamyl transpeptidase, low density lipoprotein cholesterol, oxidative stress index, triglycerides, and total oxidant status levels significantly (p < 0.05). In conclusion, this study revealed that treatment with resveratrol might protect liver tissue against the side--effects of risperidone over fatty acid synthase gene expression. Resveratrol could be an effective course of therapy for enhancing therapeutic efficacy.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Substâncias Protetoras/farmacologia , Resveratrol/farmacologia , Risperidona , Receptor fas/genética , Animais , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos , Ratos Sprague-Dawley
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