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1.
Artigo em Inglês | MEDLINE | ID: mdl-34495823

RESUMO

The novel, anaerobic, Gram-positive, rod-shaped bacterial strain, ResAG-91T, was isolated from a faecal sample of a male human volunteer. Analysis of the 16S rRNA gene sequence revealed that strain ResAG-91T showed high similarity to the type strains of Adlercreutzia equolifaciens subsp. equolifaciens and Adlercreutzia equolifaciens subsp. celatus. Analysis of the whole draft genome sequences, i.e. digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI), of strain ResAG-91T and the type strains of Adlercreutzia species revealed that strain ResAG-91T represents a novel species of the genus Adlercreutzia. The genome size of strain ResAG-91T is 2.8 Mbp and the G+C content is 63.3 mol%. The major respiratory quinone of strain ResAG-91T was MMK-5 (methylmenaquinone). Major cellular fatty acids were C15 : 0 anteiso, C14 : 0 iso and C14 : 0 2-OH. Galactose and ribose were detected as major whole cell sugars. Furthermore, the peptidoglycan type of strain ResAG-91T was A1γ with meso-diaminopimelic acid. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid, three unidentified phospholipids and five unidentified glycolipids. Strain ResAG-91T was able to metabolize the stilbene resveratrol into dihydroresveratrol. On the basis of this polyphasic approach, including phenotypical, molecular (16S rRNA gene and whole genome sequencing) and biochemical (fatty acids, quinones, polar lipids, peptidoglycan, whole cell sugars, Rapid ID32A and API20A) analyses, we propose the novel species Adlercreutzia rubneri sp. nov. with the type and only strain ResAG-91T (=DSM 111416T=JCM 34176T=LMG 31897T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Actinobacteria , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética , Resveratrol , Análise de Sequência de DNA , Vitamina K 2
2.
Shanghai Kou Qiang Yi Xue ; 30(3): 232-236, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476436

RESUMO

PURPOSE: To explore whether resveratrol dependents on the production of suppressor of cytokine signaling suppressor 3 (SOCS-3) in inhibiting mRNA production of macrophage inflammatory protein-2 (MIP-2) in osteoblasts induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e). METHODS: MC3T3-E1 cells were treated with different concentrations of resveratrol (0, 5, 10 and 20 µmol/L) and 20 µmol/L resveratrol for different time( 0, 10, 30, 60, 120 and 180 min). The expression of SOCS-3 protein was detected by Western blot. MC3T3-E1 cells were transfected with mouse SOCS3 siRNA (si-SOCS-3) and control siRNA(si-control). Reverse transcription real-time PCR(real-time RT-PCR) and Western blot was used to detect the silencing efficiency of SOCS-3. Cells were stimulated by 20 µg/mL P.e-LPS for 24 h after transfection, in the absence or presence of 20 µmol/L resveratrol for 1 h , and the changes of MIP-2 mRNA were determined by real-time RT-PCR. 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 resveratrol caused a significant increase in SOCS-3 protein expression in a dose-dependent manner. During the observation time of 180 min, SOCS-3 protein expression was the highest at 20 µmol/L resveratrol-treated osteoblasts for 60 min. The silencing efficiency of SOCS-3 mRNA was 63.7%. Transfection with SOCS-3 siRNA increased MIP-2 mRNA expression in LPS-stimulated MC3T3-E1 cells and negated the inhibitory effects of resveratrol on LPS-induced MIP-2 mRNA expression(P<0.05). CONCLUSIONS: Resveratrol inhibits the expression of MIP-2 mRNA in osteoblasts induced by P.e-LPS by up-regulating the expression of SOCS-3 protein.


Assuntos
Lipopolissacarídeos , Porphyromonas endodontalis , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Osteoblastos , RNA Mensageiro , Resveratrol/farmacologia
3.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361004

RESUMO

This article reviews evidence suggesting that a common mechanism of initiation leads to the development of many prevalent types of cancer. Endogenous estrogens, in the form of catechol estrogen-3,4-quinones, play a central role in this pathway of cancer initiation. The catechol estrogen-3,4-quinones react with specific purine bases in DNA to form depurinating estrogen-DNA adducts that generate apurinic sites. The apurinic sites can then lead to cancer-causing mutations. The process of cancer initiation has been demonstrated using results from test tube reactions, cultured mammalian cells, and human subjects. Increased amounts of estrogen-DNA adducts are found not only in people with several different types of cancer but also in women at high risk for breast cancer, indicating that the formation of adducts is on the pathway to cancer initiation. Two compounds, resveratrol, and N-acetylcysteine, are particularly good at preventing the formation of estrogen-DNA adducts in humans and are, thus, potential cancer-prevention compounds.


Assuntos
Acetilcisteína/farmacologia , Carcinogênese/efeitos dos fármacos , Estradiol/farmacologia , Estrona/farmacologia , Quinonas/farmacologia , Resveratrol/farmacologia , Animais , Antioxidantes/farmacologia , Carcinogênese/genética , Adutos de DNA , Estradiol/toxicidade , Estrogênios/farmacologia , Estrogênios/toxicidade , Estrona/toxicidade , Humanos , Quinonas/toxicidade
4.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445644

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is considered a manifestation of metabolic syndrome (MS) and is characterized by the accumulation of triglycerides and a varying degree of hepatic injury, inflammation, and repair. Moreover, peroxisome-proliferator-activated receptors (PPARs) play a critical role in the pathophysiological processes in the liver. There is extensive evidence of the beneficial effect of polyphenols such as resveratrol (RSV) and quercetin (QRC) on the treatment of liver pathology; however, the mechanisms underlying their beneficial effects have not been fully elucidated. In this work, we show that the mechanisms underlying the beneficial effects of RSV and QRC against inflammation in liver damage in our MS model are due to the activation of novel pathways which have not been previously described such as the downregulation of the expression of toll-like receptor 4 (TLR4), neutrophil elastase (NE) and purinergic receptor P2Y2. This downregulation leads to a decrease in apoptosis and hepatic fibrosis with no changes in hepatocyte proliferation. In addition, PPAR alpha and gamma expression were altered in MS but their expression was not affected by the treatment with the natural compounds. The improvement of liver damage by the administration of polyphenols was reflected in the normalization of serum transaminase activities.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Cirrose Hepática/prevenção & controle , Síndrome Metabólica/complicações , Quercetina/farmacologia , Receptores Purinérgicos/metabolismo , Resveratrol/farmacologia , Animais , Antioxidantes/farmacologia , Citocinas/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Wistar , Receptores Purinérgicos/genética
5.
Adipocyte ; 10(1): 408-411, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34402717

RESUMO

Angiotensin converting enzyme-2 (ACE2) is the cell-surface receptor enabling cellular entry of SARS-CoV-2. ACE2 is highly expressed in adipose tissue (AT), rendering AT a potential SARS-CoV-2 reservoir contributing to massive viral spread in COVID-19 patients with obesity. Although rodent and cell studies suggest that the polyphenol resveratrol alters ACE2, human studies are lacking. Here, we investigated the effects of 30-days resveratrol supplementation on RAS components in AT and skeletal muscle in men with obesity in a placebo-controlled cross-over study. Resveratrol markedly decreased ACE2 (~40%) and leptin (~30%), but did neither alter angiotensinogen, ACE and AT1R expression in AT nor skeletal muscle RAS components. These findings demonstrate that resveratrol supplementation reduces ACE2 in AT, which might dampen SARS-CoV-2 spread in COVID-19.


Assuntos
Tecido Adiposo/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Resveratrol/administração & dosagem , Tecido Adiposo/citologia , Enzima de Conversão de Angiotensina 2/genética , COVID-19/patologia , COVID-19/virologia , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Regulação para Baixo/efeitos dos fármacos , Humanos , Leptina/genética , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/patologia , Efeito Placebo , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Resveratrol/farmacologia , SARS-CoV-2/isolamento & purificação
6.
J Agric Food Chem ; 69(32): 9249-9258, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34357767

RESUMO

Resveratrol (RES) suffers from poor water solubility and extensive metabolism, which lead to low bioavailability. A phospholipid complex (PC) containing RES and a UDP-glucuronosyltransferase (UGT) inhibitor was prepared to address these two limiting factors, thereby improving RES bioavailability. First, 11 natural active ingredients metabolized by similar enzyme subtypes to RES were screened in a glucuronidation assay in liver microsomes. Then, glycyrrhetinic acid (GA), the strongest inhibitor, was prepared with RES in a PC. RES-PC was prepared as a control. As expected, the water solubility and the cumulative dissolution of RES were significantly enhanced by RES-PC and RES/GA-PC. Compared with the RES group, the AUC0-10 of RES and resveratrol-3-glucuronide (R-3-G) in the RES/GA-PC group showed increases of 2.49- and 1.70-fold, respectively, with the proportion of RES absorption to total absorption increasing 1.45 times. These results demonstrated that RES/GA-PC could improve the bioavailability of RES by increasing its water solubility and inhibiting its glucuronidation.


Assuntos
Glucuronosiltransferase , Microssomos Hepáticos , Disponibilidade Biológica , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/metabolismo , Resveratrol/metabolismo , Solubilidade , Água/metabolismo
7.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356672

RESUMO

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)-two natural stilbene polyphenols with manifold, well known biological activities-with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/tratamento farmacológico , Glucosídeos/farmacologia , Resveratrol/farmacologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Estilbenos/farmacologia , COVID-19/metabolismo , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Inibidores Enzimáticos/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/metabolismo
8.
Molecules ; 26(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34443591

RESUMO

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.


Assuntos
Aminobutiratos/farmacologia , Compostos de Bifenilo/farmacologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Resveratrol/farmacologia , Valsartana/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Combinação de Medicamentos , Interações Medicamentosas , Fibrose , Humanos , Masculino , Infarto do Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda/efeitos dos fármacos
9.
Viruses ; 13(7)2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-34372541

RESUMO

The current COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has an enormous impact on human health and economy. In search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for SARS-CoV-2 infection. Here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, exhibit potent antiviral properties against SARS-CoV-2 in vitro. First, we show that resveratrol and pterostilbene antiviral activity in African green monkey kidney cells. Both compounds actively inhibit virus replication within infected cells as reduced virus progeny production was observed when the compound was added at post-inoculation conditions. Without replenishment of the compound, antiviral activity was observed up to roughly five rounds of replication, demonstrating the long-lasting effect of these compounds. Second, as the upper respiratory tract represents the initial site of SARS-CoV-2 replication, we also assessed antiviral activity in air-liquid interface (ALI) cultured human primary bronchial epithelial cells, isolated from healthy volunteers. Resveratrol and pterostilbene showed a strong antiviral effect in these cells up to 48 h post-infection. Collectively, our data indicate that resveratrol and pterostilbene are promising antiviral compounds to inhibit SARS-CoV-2 infection. Because these results represent laboratory findings in cells, we advocate evaluation of these compounds in clinical trials before statements are made whether these drugs are advantageous for COVID-19 treatment.


Assuntos
Brônquios/virologia , COVID-19/virologia , Células Epiteliais/virologia , Resveratrol/farmacologia , SARS-CoV-2/efeitos dos fármacos , Estilbenos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia , Células Vero
10.
Front Immunol ; 12: 707287, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394108

RESUMO

Background: The outbreak of Coronavirus disease 2019 (COVID-19) has become an international public health crisis, and the number of cases with dengue co-infection has raised concerns. Unfortunately, treatment options are currently limited or even unavailable. Thus, the aim of our study was to explore the underlying mechanisms and identify potential therapeutic targets for co-infection. Methods: To further understand the mechanisms underlying co-infection, we used a series of bioinformatics analyses to build host factor interaction networks and elucidate biological process and molecular function categories, pathway activity, tissue-specific enrichment, and potential therapeutic agents. Results: We explored the pathologic mechanisms of COVID-19 and dengue co-infection, including predisposing genes, significant pathways, biological functions, and possible drugs for intervention. In total, 460 shared host factors were collected; among them, CCL4 and AhR targets were important. To further analyze biological functions, we created a protein-protein interaction (PPI) network and performed Molecular Complex Detection (MCODE) analysis. In addition, common signaling pathways were acquired, and the toll-like receptor and NOD-like receptor signaling pathways exerted a significant effect on the interaction. Upregulated genes were identified based on the activity score of dysregulated genes, such as IL-1, Hippo, and TNF-α. We also conducted tissue-specific enrichment analysis and found ICAM-1 and CCL2 to be highly expressed in the lung. Finally, candidate drugs were screened, including resveratrol, genistein, and dexamethasone. Conclusions: This study probes host factor interaction networks for COVID-19 and dengue and provides potential drugs for clinical practice. Although the findings need to be verified, they contribute to the treatment of co-infection and the management of respiratory disease.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/patologia , Biologia Computacional/métodos , Dengue/tratamento farmacológico , Dengue/patologia , Mapas de Interação de Proteínas/fisiologia , Antivirais/uso terapêutico , Quimiocina CCL2/metabolismo , Coinfecção , Vírus da Dengue/efeitos dos fármacos , Dexametasona/uso terapêutico , Regulação da Expressão Gênica/genética , Genisteína/uso terapêutico , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/metabolismo , Resveratrol/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Transdução de Sinais
11.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361023

RESUMO

Aging is an unavoidable part of life. The more aged we become, the more susceptible we become to various complications and damages to the vital organs, including the kidneys. The existing drugs for kidney diseases are mostly of synthetic origins; thus, natural compounds with minimal side-effects have attracted growing interest from the scientific community and pharmaceutical companies. A literature search was carried out to collect published research information on the effects of resveratrol on kidney aging. Recently, resveratrol has emerged as a potential anti-aging agent. This versatile polyphenol exerts its anti-aging effects by intervening in various pathologies and multi-signaling systems, including sirtuin type 1, AMP-activated protein kinase, and nuclear factor-κB. Researchers are trying to figure out the detailed mechanisms and possible resveratrol-mediated interventions in divergent pathways at the molecular level. This review highlights (i) the causative factors implicated in kidney aging and the therapeutic aspects of resveratrol, and (ii) the effectiveness of resveratrol in delaying the aging process of the kidney while minimizing all possible side effects.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Rim/efeitos dos fármacos , Resveratrol/farmacologia , Envelhecimento/metabolismo , Animais , Humanos , Rim/crescimento & desenvolvimento , Rim/metabolismo , Sirtuína 1/metabolismo
12.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443569

RESUMO

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic-hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.


Assuntos
Tecnologia de Extrusão por Fusão a Quente , Resveratrol/química , Resveratrol/farmacocinética , Disponibilidade Biológica , Preparações de Ação Retardada , Portadores de Fármacos/química , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis/química , Solubilidade
13.
Nutrients ; 13(7)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34371884

RESUMO

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68, p < 0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = -0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.


Assuntos
Hesperidina/administração & dosagem , Resistência à Insulina , Obesidade/terapia , Sobrepeso/terapia , Resveratrol/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Proteínas de Transporte/sangue , Correlação de Dados , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/terapia , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/terapia , Glicosilação/efeitos dos fármacos , Humanos , Inflamação , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Obesidade/sangue , Sobrepeso/sangue , Aldeído Pirúvico/sangue , Fator de Necrose Tumoral alfa/sangue
14.
J Agric Food Chem ; 69(35): 10036-10057, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34460268

RESUMO

Biological targeting or molecular targeting is the main strategy in drug development and disease prevention. However, the problem of "off-targets" cannot be neglected. Naturally derived drugs are preferred over synthetic compounds in pharmaceutical markets, and the main goals are high effectiveness, lower cost, and fewer side effects. Single-target drug binding may be the major cause of failure, as the pathogenesis of diseases is predominantly multifactorial. Naturally derived drugs are advantageous because they are expected to have multitarget effects, but not off-targets, in disease prevention or therapeutic actions. The capability of phytochemicals to modulate molecular signals in numerous diseases has been widely discussed. Among them, stilbenoids, especially resveratrol, have been well-studied, along with their potential molecular targets, including AMPK, Sirt1, NF-κB, PKC, Nrf2, and PPARs. The analogues of resveratrol, pterostilbene, and hydroxylated-pterostilbene may have similar, if not more, potential biological targeting effects compared with their original counterpart. Furthermore, new targets that have been discussed in recent studies are reviewed in this paper.


Assuntos
Estilbenos , Resveratrol
15.
Environ Toxicol ; 36(10): 2105-2115, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34236127

RESUMO

This work was designed to explore the protective role of resveratrol (RES) against sulfoxaflor (Sulfx)-induced reproductive toxicity in adult male rats. The animals were divided into six groups: Control group, Sulfx treated groups (79.5 and 205 mg/kg/day), RES treated group (20 mg/kg/day), RES + Sulfx treated groups (20 mg/kg Res + 79.5 or 205 mg/kg Sulfx) orally for 28 consecutive days. Testicular samples were collected from all groups at the end of the treatment period. Tissue supernatants were isolated for oxidative stress and cellular energy parameters; tissue samples were prepared for histopathological examination. In addition, caspase-3 activity was calculated to assess spermatogenesis. Finally, DNA laddering assay was performed to detect DNA fragmentation as a hallmark of apoptosis. Our results showed that Sulfx treatment induced a significant increase in testicular levels of MDA, NOx, GSSG and reduced GSH level and cellular energy parameters in a dose-dependent manner compared to the control group. The results were confirmed by histopathological study which showed pathological changes in Sulfx treated groups. A significant increase in caspase 3 and DNA fragmentation was also observed. However, concomitant administration of RES to Sulfx -treated rats showed significant modulation against Sulfx-induced reproductive toxicity and attenuated the biochemical, apoptotic and histopathological changes. In conclusion, our results suggest that exposure to Sulfx at the two selected doses induces testicular toxicity and these effects can be ameliorated by supplementation of RES.


Assuntos
Antioxidantes , Testículo , Animais , Antioxidantes/metabolismo , Apoptose , Masculino , Estresse Oxidativo , Piridinas , Ratos , Resveratrol , Compostos de Enxofre , Testículo/metabolismo
16.
Poult Sci ; 100(9): 101290, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34311322

RESUMO

Avian spermatozoa are highly susceptible to reactive oxygen species (ROS) produced during the cryopreservation. The aim of the current study was to investigate the antioxidant effects of resveratrol (RSV) during rooster semen cryopreservation. Changes in expression of AMP-activated protein kinase as a possible mechanism behind the beneficial effects of resveratrol were also evaluated. Semen samples were collected from ten Ross broiler breeders (52-wk) using abdominal massage, then divided into 4 equal aliquots and cryopreserved in Beltsville extender that contained different concentrations (0 µM, 0.01µM, 0.1µM, and 1µM) of RSV. higher percentage (P < 0.05) of total motility and membrane integrity was observed in RSV-0.1 compared to the other frozen groups. Moreover, higher percentage of sperm mitochondrial activity was observed in the RSV-0.01 and RSV-0.1 compared to the frozen control (P < 0.05). The lowest percentage of apoptotic like changes was found in the RSV-0.1 in comparison to the other groups (P < 0.05). RSV-0.01 and RSV-1 groups produced the lowest levels of H2O2 and O2- compared to the other frozen groups, respectively. Malondialdehyde (MDA) concentration, velocity average path (VAP), and linearity (LIN) were not affected by different concentrations of RSV (P > 0.05). We observed a dose-dependent increase in AMP-activated protein kinase expression in groups exposed to RSV. Thus, RSV-1 increased AMP-activated protein kinase phosphorylation but had no positive effects on post thaw sperm parameters. Our findings suggest that RSV-0.1 improve thawed sperm functions, and these effects might be mediated through activation of AMP-activated protein kinase.


Assuntos
Preservação do Sêmen , Sêmen , Animais , Galinhas , Criopreservação/veterinária , Crioprotetores/farmacologia , Peróxido de Hidrogênio , Masculino , Resveratrol/farmacologia , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária , Motilidade Espermática , Espermatozoides
17.
Molecules ; 26(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279413

RESUMO

Malaria i a serious health problem caused by Plasmodium spp. that can be treated by an anti-folate pyrimethamine (PYR) drug. Deferiprone (DFP) is an oral iron chelator used for the treatment of iron overload and has been recognized for its potential anti-malarial activity. Deferiprone-resveratrol hybrids (DFP-RVT) have been synthesized to present therapeutic efficacy at a level which is superior to DFP. We have focused on determining the lipophilicity, toxicity and inhibitory effects on P. falciparum growth and the iron-chelating activity of labile iron pools (LIPs) by DFP-RVT. According to our findings, DFP-RVT was more lipophilic than DFP (p < 0.05) and nontoxic to blood mononuclear cells. Potency for the inhibition of P. falciparum was PYR > DFP-RVT > DFP in the 3D7 strain (IC50 = 0.05, 16.82 and 47.67 µM, respectively) and DFP-RVT > DFP > PYR in the K1 strain (IC50 = 13.38, 42.02 and 105.61 µM, respectively). The combined treatment of DFP-RVT with PYR additionally enhanced the PYR activity in both strains. DFP-RVT dose-dependently lowered LIP levels in PRBCs and was observed to be more effective than DFP at equal concentrations. Thus, the DFP-RVT hybrid should be considered a candidate as an adjuvant anti-malarial drug through the deprivation of cellular iron.


Assuntos
Antimaláricos/farmacologia , Deferiprona/farmacologia , Eritrócitos/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Resveratrol/farmacologia , Antioxidantes/farmacologia , Eritrócitos/parasitologia , Humanos , Quelantes de Ferro/farmacologia , Malária Falciparum/parasitologia
18.
Int J Pharm ; 606: 120877, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34252522

RESUMO

Resveratrol (RVT) is one of the potent anticancer phytochemicals which has shown promising potential for breast cancer therapy. However, its short half-life and low bioavailability is a major hurdle in its effective use. In this study, we have developed nanostructured lipid carriers (NLCs) of RVT to enable localized delivery of the drug to the breast tissues using microneedle arrays to improve effectiveness. The NLCs were optimized using the Design of Experiments approach and characterized for their particle size, polydispersity index, zeta potential and entrapment efficiency. The RVT-NLCs delivered using microneedle array 1200 showed a higher permeation of RVT across the skin with lower skin retention compared to pure RVT. Further, RVT-NLCs showed higher anticancer activity on MDA-MB-231 breast cancer cell lines and enhanced internalization compared to pure RVT. Moreover, the RVT-NLCs were found to inhibit the migration of MDA-MB-231 breast cancer cell lines. Preclinical studies in rats showed that RVT-NLCs delivered via microneedles demonstrated a remarkable increase in the Cmax, Tmax and AUC0-inf, and a higher localization in breast tissue compared to pure RVT administered orally. These results suggests that the RVT-NLCs administered by microneedle array system is an effective strategy for the local delivery of RVT for breast cancer therapy.


Assuntos
Nanoestruturas , Neoplasias , Animais , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Lipídeos , Tamanho da Partícula , Ratos , Resveratrol
19.
Yonsei Med J ; 62(8): 691-701, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34296546

RESUMO

PURPOSE: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. MATERIALS AND METHODS: The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. RESULTS: Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a. We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. CONCLUSION: Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Resveratrol/farmacologia , Regulação para Cima
20.
Eur J Pharm Sci ; 165: 105930, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265406

RESUMO

Drugs targeting epigenetic mechanisms are attracting the attention of scientists since it was observed that the modulation of this post-translational apparatus, could help to identify innovative therapeutic strategies. Among the epigenetic druggable targets, the positive modulation of SIRT1 has also been related to significant cardioprotective effects. Unfortunately, actual SIRT1 activators (natural products and synthetic molecules) suffer from several drawbacks, particularly poor pharmacokinetic profiles. Accordingly, in this article we present the development of an integrated screening platform aimed at identifying novel SIRT1 activators with favorable drug-like features as cardioprotective agents. Encompassing several competencies (in silico, medicinal chemistry, and pharmacology), we describe a multidisciplinary approach for rapidly identifying SIRT1 activators and their preliminary pharmacological characterization. In the first step, we virtually screened an in-house chemical library comprising synthetic molecules inspired by nature, against SIRT1 enzyme. To this end, we combined molecular docking-based approach with the estimation of relative ligand binding energy, using the crystal structure of SIRT1 enzyme in complex with resveratrol. Eleven computational hits were identified, synthesized and tested against the isolated enzyme for validating the in silico strategy. Among the tested molecules, five of them behave as SIRT1 enzyme activators. Due to the superior response in activating the enzyme and its favorable calculated physico-chemical properties, compound 8 was further characterized in ex vivo studies on isolated and perfused rat hearts submitted to ischemia/reperfusion (I/R) period. The pharmacological profile of compound 8, suggests that this molecule represents a prototypic SIRT1 activator with satisfactory drug-like profile, paving the way for developing novel epigenetic cardioprotective agents.


Assuntos
Cardiotônicos , Sirtuína 1 , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Simulação de Acoplamento Molecular , Ratos , Resveratrol , Bibliotecas de Moléculas Pequenas
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