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1.
Cell Prolif ; 53(3): e12773, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020692

RESUMO

OBJECTIVES: SIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)-induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA-induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p-Akt pathway. MATERIALS AND METHODS: The rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio-informatics prediction. RESULTS: Chronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA-induced apoptosis was associated with SIRT1-related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO-1 and E-cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA-induced higher permeability of alveolar epithelium. CONCLUSIONS: MA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA-induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p-Akt pathway.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Antioxidantes/uso terapêutico , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Metanfetamina/efeitos adversos , Resveratrol/uso terapêutico , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo
2.
Life Sci ; 246: 117422, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32057903

RESUMO

AIMS: This study aimed to investigate the effects of resveratrol (3, 4', 5-trihydroxystilbene, RES) on osteoporosis and the role of SIRT1/FoxO1 pathway in the process. MAIN METHODS: In vivo, mice were divided into 3 groups, Sham, ovariectomized (OVX) and OVX-RES group. Micro-CT, histology and histomorphometry were conducted to detect details of bone mass and microstructure. The expression of osteoblast markers was tested by Real-time qPCR and serum markers which reflected bone formation and resorption were analyzed by enzyme-linked immunosorbent assay (ELISA). Besides, we assayed sirtuin 1 (SIRT1) expression and the concentration of serum superoxide dismutase (SOD). In vitro, osteoblasts were seperated into 3 groups: control, H2O2 (hydrogen peroxide, H2O2) and H2O2-RES group. Cell proliferation, differentiation and apoptosis were detected. In addition, we tested intracellular reactive oxygen species (ROS) formation and SOD activity detection of osteoblasts. The SIRT1, acetylated FoxO1 (Ac-FoxO1) and nuclear FoxO1 (Nu-FoxO1) expression were detected by western blot. KEY FINDINGS: Results revealed that RES could ameliorate bone loss and promote osteogenesis by reinforcing resistance of oxidative stress in OVX mice. RES enhanced proliferation, differentiation and suppressed apoptosis of H2O2-treated osteoblasts. In this process, SIRT1 was upregulated and the level of Nu-FoxO1, which had high transcriptional activity to regulate redox balance, significantly increased. SIGNIFICANCE: Oxidative stress plays a crucial role in osteoporosis. RES can reinforce resistance to oxidative damage and hence promote osteogenesis via the activation of SIRT1/FoxO1 signaling pathway, which provides a new idea for the prevention and treatment of osteoporosis.


Assuntos
Antioxidantes/uso terapêutico , Proteína Forkhead Box O1/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Resveratrol/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Animais , Antioxidantes/farmacologia , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Osteoporose/diagnóstico por imagem , Osteoporose/metabolismo , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol/farmacologia , Superóxido Dismutase/sangue , Microtomografia por Raio-X
3.
Life Sci ; 245: 117349, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31981632

RESUMO

AIMS: To explore whether the combination of atorvastatins and resveratrol is superior to each individual drug alone regarding re-endothelialization after drug-eluting stents (DESs) implantation. MATERIALS AND METHODS: Ninety-four rabbits were randomized into control, atorvastatin, resveratrol, and combined medication groups. Abdominal aorta injury was induced via ballooning, followed by DES implantation. Neointimal formation and re-endothelialization after stent implantation were assessed via optical coherence tomography and scanning electron microscopy. The effects of resveratrol and atorvastatin on bone marrow-derived mesenchymal derived stem cells (BMSCs) were assessed. KEY FINDINGS: Compared with the findings in the resveratrol and atorvastatin groups, the neointimal area and mean neointimal thickness were greater in the combined medication group, which also exhibited improved re-endothelialization. Compared with the effects of monotherapy, combined treatment further protected BMSCs against rapamycin-induced apoptosis and improved cell migration. Combined medication significantly upregulated Akt, p-Akt, eNOS, p-eNOS, and CXCR4 expression in BMSCs compared with the effects of monotherapy, and these effects were abolished by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. SIGNIFICANCE: The combination of atorvastatin and resveratrol has the potential of accelerating re-endothelialization after stent implantation, reducing the risk of thrombosis and improving the safety of DESs.


Assuntos
Atorvastatina/uso terapêutico , Implante de Prótese Vascular/métodos , Stents Farmacológicos , Endotélio Vascular/efeitos dos fármacos , Resveratrol/uso terapêutico , Animais , Aorta Abdominal/cirurgia , Aorta Abdominal/ultraestrutura , Atorvastatina/administração & dosagem , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Endotélio Vascular/crescimento & desenvolvimento , Endotélio Vascular/ultraestrutura , Hylobatidae , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Coelhos , Ratos , Ratos Sprague-Dawley , Resveratrol/administração & dosagem , Tomografia de Coerência Óptica
4.
Life Sci ; 245: 117350, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31982401

RESUMO

Resveratrol is an important phenolic phytochemical from the therapeutic perspective. It has therapeutic impacts over wide range of diseases, especially the ones related to oxidative stress. Resveratrol, being primarily a potent anti-oxidant phytochemical, has significant impact against major diseases as inflammatory disorders, diabetes, and cancer. In the current review article, we intend to highlight the molecular aspects of the mechanism of action of resveratrol against major diabetic implications, namely, retinopathy and neuropathy. Both these diabetic implications are among the first fallouts of chronic hyperglycaemia. Resveratrol, via multiple molecular pathways, tend to attenuate and reverse these deformity and other disease-causing implications.


Assuntos
Antioxidantes/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Antioxidantes/farmacologia , Humanos , Resveratrol/farmacologia
5.
Life Sci ; 245: 117362, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31996295

RESUMO

The prominent feature of obstructive sleep apnea (OSA) is chronic intermittent hypoxia (CIH). Given the strong antioxidant ability of resveratrol against oxidative stress, we evaluated the potential protective effects of resveratrol on myocardial injury induced by CIH. Twenty-four rats were divided into normal control group, CIH group, CIH plus resveratrol treated (CIH + Res) group, and resveratrol treated control (Res) group. We proved that CIH impaired cardiac structure and function with an increase in oxidative stress, endoplasmic reticulum (ER) stress and NOD-like receptors (NLRP3) inflammasome induction in heart, which was attenuated after resveratrol administration. NLRP3 inflammasome blockade by resveratrol appeared to be mediated by activating AMP-activated Protein Kinase (AMPK), which could restrain mTOR/TTP/NLRP3 mRNA signalling. Furthermore, resveratrol attenuated CIH-induced oxidative stress through elevation antioxidant molecules expression via NF-E2-related factor-2 (Nrf2). Moreover, AMPK may play a role in Nrf2/HO-1 signalling by resveratrol. These results expand our understanding of the myocardial protective mechanism of resveratrol during CIH and suggest that resveratrol treatment may be useful to counteract OSA-associated cardiac injury.


Assuntos
Antioxidantes/uso terapêutico , Hipóxia/complicações , Inflamassomos/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Resveratrol/uso terapêutico , Animais , Antioxidantes/farmacologia , Western Blotting , Ecocardiografia , Imunofluorescência , Inflamassomos/metabolismo , Masculino , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol/farmacologia
6.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 72-83, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31844893

RESUMO

Type 2 diabetes increases the risk for cancer. Centrosome amplification can initiate tumorigenesis. We have described that type 2 diabetes increases the centrosome amplification of peripheral blood mononuclear cells, with high glucose, insulin, and palmitic acid as the triggers, which suggests that centrosome amplification is a candidate biological mechanism linking diabetes to cancer. In this study, we aimed to further investigate the signaling pathways of the diabetes-associated centrosome amplification and to examine whether and how resveratrol inhibits the centrosome amplification. The results showed that treatment with high glucose, insulin, and palmitic acid, alone or in combination, could increase the protein levels of phospho-protein kinase C alpha (p-PKCα), phospho-p38 mitogen-activated protein kinases (p-p38), c-myc, and c-jun, as well as the mRNA levels of c-myc and c-jun. PKCα inhibitor could inhibit the treatment-induced increase in the protein levels of p-p38, c-myc, and c-jun. Inhibitor or siRNA of p38 was also able to inhibit the treatment-induced increase in the levels of p-p38, c-myc, and c-jun. Meanwhile, knockdown of c-myc or c-jun did not alter the treatment-induced increase in the phosphorylation of PKCα or p38. Importantly, inhibition of the phosphorylation of PKCα or p38 and knockdown of c-myc or c-jun could attenuate the centrosome amplification. In diabetic mice, the levels of p-PKCα, p-p38, c-myc, and c-jun were all increased in the colon tissues. Interestingly, resveratrol, but not metformin, was able to attenuate the treatment-induced increase in the levels of p-PKCα, p-p38, c-myc, and c-jun, as well as the centrosome amplification. In conclusion, our results suggest that PKCα-p38 to c-myc/c-jun is the signaling pathway of the diabetes-associated centrosome amplification, and resveratrol attenuates the centrosome amplification by inhibiting this signaling pathway.


Assuntos
Centrossomo/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Proteína Quinase C-alfa/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Centrossomo/metabolismo , Colo/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Técnicas de Silenciamento de Genes , Glucose/farmacologia , Células HCT116 , Humanos , Insulina/farmacologia , Camundongos , Ácido Palmítico/farmacologia , Fosforilação/efeitos dos fármacos , Proteína Quinase C-alfa/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Interferente Pequeno/genética , Estreptozocina/efeitos adversos , Estreptozocina/farmacologia , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/genética
7.
Int J Exp Pathol ; 100(5-6): 337-349, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31867811

RESUMO

The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1-mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia-reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR-treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1-related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR-treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti-apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK-Mfn1 pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Encéfalo/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Resveratrol/farmacocinética , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Linhagem Celular , Homeostase/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Dinâmica Mitocondrial/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Resveratrol/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
8.
Curr Drug Res Rev ; 11(2): 111-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875783

RESUMO

BACKGROUND: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis. METHODS: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs' doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers. RESULTS: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis. CONCLUSION: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.


Assuntos
Antioxidantes/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Resveratrol/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Pulmão/patologia , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos da radiação , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/patologia , Pneumonite por Radiação/patologia
9.
Medicine (Baltimore) ; 98(46): e17938, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725648

RESUMO

BACKGROUND: This study will aim to systematically explore the efficacy of resveratrol for the treatment of patients with ulcerative colitis (UC). METHODS: We will search the electronic databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure up to the September 1, 2019 for randomized controlled trials (RCTs) that report on UC who have undergone resveratrol compared with other interventions. All electronic databases will be searched without restrictions of language. Two authors will independently conduct study screen, data extraction, and risk of bias assessment. Any disagreements between 2 authors will be resolved with a third author by discussion or consultation if it is necessary. RevMan 5.3 software will be applied for statistical analysis. RESULTS: Outcomes include clinical remission, improvement of clinical symptoms, maintenance of remission, relapse rate, endoscopic assessment, histological assessment, quality of life, and adverse events. CONCLUSION: This study will provide most recent evidence of resveratrol for the treatment of patients with UC. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019150849.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Resveratrol/uso terapêutico , Colite Ulcerativa/patologia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Projetos de Pesquisa , Resveratrol/efeitos adversos
10.
Med Sci Monit ; 25: 7675-7683, 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31606730

RESUMO

BACKGROUND Endothelial progenitor cells (EPCs) play an important role in therapeutic angiogenesis. Besides, resveratrol (RSV) exerts many pharmacological functions in regulation of cell function. Furthermore, microRNAs (miRNAs) have been considered to be of great significance in biological process. In this study, we aimed to investigate the effect of RSV on EPCs and its potential mechanism that involved in recanalization of venous thrombosis. MATERIAL AND METHODS EPCs were treated with RSV, and angiogenic functions was evaluated by tube formation and migration assays. miR-542-3p expression level in EPCs was assessed and exogenously modified. Bioinformatic analysis was applied to detect the potential target of miR-542-3p. Effects of RSV treatment in vivo venous thrombosis rat model were evaluated. RESULTS RSV enhanced angiogenic function of EPCs and decreased expression of miR-542-3p. Dual luciferase reporter gene and western blot results confirmed angiopoietin-2 (ANGPT2) was a direct target of miR-542-3p. It was found that inhibition of miR-542-3p contributed to angiogenesis of EPCs and elevated ANGPT2 protein level. Finally, in a rat model of venous thrombosis, RSV-treated EPCs promoted recanalization of thrombi. CONCLUSIONS We demonstrated that RSV can contribute to progenitor cells angiogenesis via miR-542-3p by targeting ANGPT2, subsequently enhanced recanalization of thrombi.


Assuntos
Angiopoietina-2/metabolismo , Células Progenitoras Endoteliais/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Resveratrol/uso terapêutico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/genética , Adulto , Animais , Sequência de Bases , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Masculino , MicroRNAs/genética , Ratos Nus , Resveratrol/farmacologia , Trombose Venosa/patologia
11.
Phytother Res ; 33(12): 3153-3162, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31475415

RESUMO

The aim of the present randomized controlled trial was to evaluate the effect of a micronized resveratrol supplement on glycemic status, lipid profile, and body composition in patients with type 2 diabetes mellitus (T2DM). A total of 71 overweight patients with T2DM (body mass index ranged 25-30) were randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. Anthropometric indices and biochemical indices including lipid and glycemic profile were measured before and after the intervention. In adjusted model (age, sex, and baseline body mass index), resveratrol decreased fasting blood sugar (-7.97±13.6 mg/dL, p=0.05) and increased high density lipoprotein (3.62±8.75 mg/dL, p=0.01) levels compared with placebo. Moreover, the mean difference in insulin levels reached significance (-0.97±1.91, µIU/mL, p= 0.02). However, no significant differences were observed for anthropometric measures. It was found that 8-week resveratrol supplementation produced useful effects on some cardio-metabolic parameters in patients with T2DM. More studies are needed to confirm these findings.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resveratrol/uso terapêutico , Adulto , Composição Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resveratrol/farmacologia , Fatores de Risco
12.
Phytother Res ; 33(12): 3064-3089, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31515899

RESUMO

Naturally occurring phytochemicals or plant derivatives are now being explored extensively for their health's benefits and medicinal uses. The therapeutic effect of phytochemicals has been reported in several pathophysiological settings such as inflammatory disorders, metabolic disorders, liver dysfunction, neurodegenerative disorders, and nephropathies. However, the most warranted therapeutic effects of phytochemicals were mapped to their anticancerous and chemopreventive action. Moreover, combining phytochemicals with standard chemotherapy has shown promising results in cancer therapy with minimal side effects and better efficacy. Many phytochemicals, like curcumin, resveratrol, and epigallocatechin-3-gallate, have been extensively investigated for their chemopreventive as well as chemotherapeutic effects. However, poor bioavailability, low solubility, hydrophobicity, and obscure target specificity restrict their therapeutic applications in the clinic. There has been a continually increasing interest to formulate nanoformulations of phytochemicals by using various nanocarriers, such as liposomes, micelles, nanoemulsions, and nanoparticles, to improve their bioavailability and target specificity, thereby maximizing the therapeutic potential. In the present review, we have summarized chemopreventive as well as chemotherapeutic action of some common phytochemicals and their major limitations in clinical application. Also, we have given an overview of strategies that can improve the efficacy of phytochemicals for their chemotherapeutic value in clinical settings.


Assuntos
Catequina/análogos & derivados , Quimioprevenção/métodos , Curcumina/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Resveratrol/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Curcumina/farmacologia , Humanos , Compostos Fitoquímicos/farmacologia , Resveratrol/farmacologia
13.
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
14.
Diabetes Metab Syndr ; 13(4): 2769-2774, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405706

RESUMO

BACKGROUND: Diabetes mellitus and periodontal disease are two common and chronic diseases with bidirectional relationship influence public health and quality of life. The aims of this study was to study the impact of resveratrol supplementation in adjunct with non-surgical periodontal therapy on inflammatory, antioxidant, and periodontal markers in patients with type 2 diabetes with periodontal disease. MATERIALS AND METHODS: In this randomized clinical trial, 43 patients with diabetes and chronic periodontitis were randomly allocated into two intervention and control groups receiving either resveratrol supplements or placebo for 4 weeks. Serum levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), total antioxidant capacity (TAC) and clinical attachment loss (CAL) as the main index of periodontal marker were measured pre-intervention and post-intervention. RESULTS: In the intervention group, the mean serum level of IL6 was reduced significantly (P = 0.039) post-intervention (2.19 ±â€¯1.09 and 1.58 ±â€¯1.06). No significant differences were seen in the mean levels of IL6, TNFα, TAC and CAL between two groups post-intervention. CONCLUSIONS: It is suggested that daily consumption of resveratrol supplement may not change TNFα, TAC and CAL, but it would be beneficial in reducing serum levels of IL6. Therefore, further studies are suggested to investigate the effects of resveratrol supplementation along with NST on periodontal status.


Assuntos
Antioxidantes/metabolismo , Biomarcadores/metabolismo , Periodontite Crônica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Nutricionais , Mediadores da Inflamação/metabolismo , Resveratrol/uso terapêutico , Adulto , Antioxidantes/uso terapêutico , Estudos de Casos e Controles , Periodontite Crônica/complicações , Periodontite Crônica/tratamento farmacológico , Periodontite Crônica/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
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
16.
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
17.
Mol Cell Biochem ; 460(1-2): 217-224, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280437

RESUMO

Resveratrol (RSV) is a natural polyphenolic compound having antioxidant effects. This study was designed to investigate the protective effects of resveratrol against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ)-induced diabetic rats. STZ was injected intraperitonally (i.p.) to 18 Sprague-Dawley albino rats, which were divided into three groups, each having six rats. First group was non-treated diabetic group (D), second diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period (D + I/R), and third diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period and treated with 20 mg/kg/day oral RSV before 30 min I/R injury (D + I/R + RSV). At the end of the experimental period, animals were decapitated, and blood samples were collected to determine tissue tumor necrosis factor-α (TNF-α) levels. Liver and lung tissue samples were obtained for the evaluation of biochemical parameters including malondialdehyde (MDA) and glutathione (GSH) levels and histopathological examinations. Compared to control, I/R injury resulted in decreases in GSH levels and increases in MDA levels. Tissue TNF-α levels were also increased in the D + I/R group compared to D group. Treatment with RSV prevented the alterations on biochemical parameters and histopathological changes induced by I/R. We demonstrate that in diabetic rats, hepatic I/R injury is associated with an augmented inflammatory response and oxidative stress, while RSV pre-treatment significantly decreased these responses. Larger clinical studies are desirable to determine the exact role(s) of RSV on hepatic I/R injury among diabetic subjects.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Fígado/patologia , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Malondialdeído/metabolismo , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Resveratrol/farmacologia , Estreptozocina , Fator de Necrose Tumoral alfa/metabolismo
18.
Ulus Travma Acil Cerrahi Derg ; 25(4): 343-349, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31297782

RESUMO

BACKGROUND: The present study investigated the therapeutic effect of resveratrol on cardiac injury resulting from blunt chest trauma and the utility of endocan as a biomarker of the inflammation process using rats. METHODS: The rats were randomly divided into the following four groups (n=7 in each group): a control group (no treatment or trauma); trauma-induced group (trauma group); resveratrol group (resveratrol 0.3 mg/kg administered via the intraperitoneal [i.p.] route group); and resveratrol + trauma group (resveratrol 0.3 mg/kg administered via the i.p. route 1 hour prior to the induction of trauma). RESULTS: The immunoreactivity of tumor necrosis factor-α and inducible nitric oxide synthase in the trauma group was increased, whereas the reaction intensity in resveratrol + trauma group was deceased. The mean endocan values of the differed between the groups (p<0.001). The mean endocan value in the resveratrol + trauma group was higher than that of the other groups. CONCLUSION: Resveratrol exhibited anti-inflammatory and antioxidant effects in lung injury after blunt chest trauma and contributed favorably to the treatment process. We believe that there is a need for further studies on the clinical use of endocan as a biomarker of inflammation in cardiac injury after blunt chest trauma.


Assuntos
Antioxidantes/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Proteoglicanas/metabolismo , Resveratrol/uso terapêutico , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Animais , Biomarcadores , Insuficiência Cardíaca/etiologia , Inflamação/tratamento farmacológico , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Proteoglicanas/análise , Distribuição Aleatória , Ratos , Fator de Necrose Tumoral alfa/metabolismo
19.
Int J Mol Sci ; 20(14)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319465

RESUMO

A large number of preclinical studies suggest the involvement of resveratrol in the prevention and treatment of eye diseases induced by oxidative stress and inflammation. We tested the hypothesis that resveratrol influences many pathways of in vitro and in vivo models of diabetic retinopathy through a systematic literature review of original articles. The review was conducted in accordance with the PRISMA guidelines. A literature search of all original articles published until April 2019 was performed. The terms "resveratrol" in combination with "retina", "retinal pathology", "diabetic retinopathy" and "eye" were searched. Possible biases were identified with the adopted SYRCLE's tool. Eighteen articles met inclusion/exclusion criteria for full-text review. Eleven of them included in vitro experiments, 11 studies reported in vivo data and 3 studies described both in vitro and in vivo experiments. Most of the in vivo studies did not include data that would allow exclusion of bias risks, according to SYRCLE's risk of bias tool. Both in vitro and in vivo data suggest anti-apoptotic, anti-inflammatory and anti-oxidative actions of resveratrol in models of diabetic retinopathy. However, results on its anti-angiogenic effects are contradictory and need more rigorous studies.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Humanos , Camundongos
20.
Nutrients ; 11(7)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319485

RESUMO

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.


Assuntos
Antioxidantes/uso terapêutico , Nefropatias/tratamento farmacológico , Resveratrol/uso terapêutico , Humanos
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