Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis / 生物医学与环境科学（英文）

OBJECTIVE@#This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol (RSV) regulate necroptosis during Vibrio vulnificus (V. vulnificus)-induced sepsis and the potential mechanism.@*METHODS@#The effect of RSV on V. vulnificus cytolysin (VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses were performed to elucidate the effect and mechanism of RSV on necroptosis in a V. vulnificus-induced sepsis mouse model.@*RESULTS@#RSV relieved necroptosis induced by VVC in RAW264.7 and MLE12 cells. RSV also inhibited the inflammatory response, had a protective effect on histopathological changes, and reduced the expression level of the necroptosis indicator pMLKL in peritoneal macrophages, lung, spleen, and liver tissues of V. vulnificus-induced septic mice in vivo. Pretreatment with RSV downregulated the mRNA of the necroptosis indicator and protein expression in peritoneal macrophages and tissues of V. vulnificus-induced septic mice. RSV also improved the survival of V. vulnificus-induced septic mice.@*CONCLUSION@#Our findings collectively demonstrate that RSV prevented V. vulnificus-induced sepsis by attenuating necroptosis, highlighting its potency in the clinical management of V. vulnificus-induced sepsis.

Potential neuroprotective of trans resveratrol a promising agent tempeh and soybean seed coats-derived against betaamyloid neurotoxicity on primary culture of nerve cells induced by 2-methoxyethanol / Potencial neuroprotetor do agente trans-resveratrol em cascas de sementes de soja e tempê derivadas da neurotoxicidade beta-amiloide na cultura primária de células nervosas induzidas pelo 2-metoxietanol

Resveratrol, a natural polyphenol found in tempeh, has not been investigated especially in vitro as a neuroprotective agent against 2-methoxyethanol (2-ME)-induced beta-amyloid cytotoxicity. Beta amyloid peptides (Aβ) could initiate neurotoxic events and neuron-inflammatory response via microglial activation. However, it remains unknown whether the neurotoxic effect of beta-amyloid and/or associated with the potential of 2-ME to induce neurotoxic effects on primary culture of nerve cells induced by 2-ME. This study investigated potential neuroprotective of trans-resveratrol a promising agent tempeh and soybean seed coats-derived against beta amyloid cytotoxicity on primary culture of nerve cells induced by 2-methoxyethanol. Biotium and MTT assays were used to analyze neurons, which were isolated from the cerebral cortex of fetal mice at gestation day 19 (GD-19). A standard solution of 2-methoxyethanol was dosed at 10 μL. The cultured cells were randomly divided into the following groups: (1) 2-ME group + resveratrol standard, (2) 2-ME group + resveratrol isolated from tempeh, (3) 2-ME group + resveratrol isolated from soybean seed coats, and (4) the control group, without the addition of either 2-ME or resveratrol. Exposure of the primary cortical neuron cells to beta-amyloid monoclonal antibody pre-incubated for 24 h with 10 µL of 4.2 µg/mL resveratrol and 7.5 mmol/l 2-methoxy-ethanol additions. Here, we report that the addition of 2-ME and resveratrol (standard and isolated from tempeh) of cell culture at concentrations of 1.4, 2.8 and 4.2 µg/mL showed that the majority of neurons grew well. In contrast, after exposure to 2-ME and Beta-amyloid, showed that glial activated. These findings demonstrate a role for resveratrol in neuroprotective-neurorescuing action.

O resveratrol, um polifenol natural encontrado em tempê, não foi investigado apenas in vitro como agente neuroprotetor contra a citotoxicidade beta-amiloide induzida por 2-metoxietanol (2-ME). Os peptídeos beta amiloides (Aβ) podem iniciar eventos neurotóxicos e resposta inflamatória dos neurônios via ativação microglial. No entanto, permanece desconhecido se o efeito neurotóxico do peptídeo beta-amiloide associado ao potencial do 2-ME causa efeitos neurotóxicos na cultura primária de células nervosas induzidas pelo 2-ME. Este estudo investigou o potencial neuroprotetor do agente trans-resveratrol em cascas de sementes de soja e tempê derivadas da citotoxicidade beta-amiloide na cultura primária de células nervosas induzidas pelo 2-metoxietanol. Ensaios de biotium e MTT foram utilizados para analisar os neurônios isolados do córtex cerebral de camundongos fetais no dia da gestação 19 (GD-19). As células cultivadas foram divididas aleatoriamente nos seguintes grupos: (1) grupo 2-ME + padrão de resveratrol; (2) grupo 2-ME + resveratrol isolado de tempê; (3) grupo 2-ME + resveratrol isolado de cascas de sementes de soja; e (4) grupo controle, sem a adição de 2-ME ou resveratrol. Houve exposição das células primárias dos neurônios corticais ao anticorpo monoclonal beta-amiloide pré-incubado por 24 horas, com 10 µL de 4,2 µg/mL de resveratrol, e adições de 7,5 mmol/l de 2-metoxietanol. A adição de 2-ME e resveratrol (padrão e isolado do tempê) da cultura de células nas concentrações de 1,4, 2,8 e 4,2 µg/mL mostrou que a maioria dos neurônios cresceu bem. Por outro lado, após a exposição ao 2-ME e beta-amiloide, a glia foi ativada. Esses achados demonstram um papel do resveratrol na ação neuroprotetora e de neurorresgate.

Resveratrol as an anti-asthmatic agent: could this stilbenoid help against COVID-19 in any way? a meta-analysis / Resveratrol como agente antiasmático: ¿podría este estilbenoide ayudar contra el COVID-19 de alguna manera? un metaanálisis

Resveratrol is a phenolic phytoconstituent found in many plants. This molecule has always caught the attention of scientists because of biological potentials such as inhibition of inflammation, oxidative stress and platelet aggregation as well as to prevent/protect against cardiovascular and neurodegenerative disease/disorders. Literature search have been conducted over resveratrol in covid-19 and asthma studies published in Pubmed and Google Scholars until 30 September 2020. The criteria used in the literature review were determined and were reviewed works on resveratrol including 368 articles and 47 articles on covid-19 and asthma, respectively. As a result of meta-analysis, TNF-α values of the studies showed a significant difference (heterogeneity) of I2=68.39% from each other in total (Cohran Q:6.33, p<0.0423). This study shows that resveratrol would have a potential to reduce ARDS symptoms, by suppressing the cytokine storm and severe inflammation caused by SARS-CoV-2, and by showing strong activity against various types of DNA/RNA viruses.

El resveratrol es un fitoconstituyente fenólico que se encuentra en muchas plantas. Esta molécula siempre ha llamado la atención de los científicos debido a sus potenciales biológicos como la inhibición de la inflamación, el estrés oxidativo y la agregación plaquetaria, así como para prevenir/proteger contra enfermedades/trastornos cardiovasculares y neurodegenerativos. Se han realizado búsquedas bibliográficas sobre resveratrol en covid-19 y estudios sobre asma publicados en Pubmed y Google Scholars hasta el 30 de septiembre de 2020. Se determinaron los criterios utilizados en la revisión bibliográfica y se revisaron trabajos sobre resveratrol que incluyen 368 artículos y 47 artículos sobre covid-19 y asma, respectivamente. Como resultado del metanálisis, los valores de TNF-α de los estudios mostraron una diferencia significativa (heterogeneidad) de I2=68,39% entre sí en total (Cohran Q: 6,33, p<0,0423). Este estudio muestra que el resveratrol podría reducir los síntomas del ARDS al suprimir la tormenta de citocinas y la inflamación severa causada por el SARS-CoV-2, y al mostrar una fuerte actividad contra varios tipos de virus de ADN/ARN.

Resveratrol alleviates Kawasaki disease-induced myocardial injury via inhibition of apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#To explore the effect of resveratrol (Res) on Kawasaki disease (KD)-induced myocardial injury and to evaluate its effect on apoptosis and autophagy.@*METHODS@#Forty-eight juvenile male Sprague Dawley rats were randomly divided into a control group, a Res group, a lactobacillus casei cell wall extract (LCWE)-induced Kawasaki disease group (KD group), and a LCWE-induced Kawasaki disease + Res treatment group (Res+KD group). The control group was intraperitoneally injected with saline. The Res group was intraperitoneally injected with resveratrol (100 mg/kg). The KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL). The Res+KD group was intraperitoneally injected with 0.5 mL LCWE (1 mg/mL) and resveratrol (100 mg/kg). After 4 weeks, the left ventricular ejection fraction (LVEF) and short axis shortening rate (LVFS) were detected by echocardiography. The apoptotic rate was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining. The levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), microtubule-associated protein 1 light chain 3β (LC3B), Beclin-1, autophagy related 5 (Atg5) and sequestosome-1 (p62) were detected by Western blotting. The formation of autophagosome was observed under transmission electron microscope.@*RESULTS@#There was no significant difference in the above-mentioned indexes between the control group and the Res group (all @*CONCLUSIONS@#Res can attenuate the KD-induced myocardial injury via inhibiting the apoptosis and autophagy.

Resveratrol in Alzheimers disease: a review of pathophysiology and therapeutic potential / Resveratrol na doença de Alzheimer: uma revisão sobre fisiopatologia e potencial terapêutico

ABSTRACT Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible loss of cognitive function. The presence of senile plaques is one of the pathological markers of the disease and is associated with the onset of neuroinflammatory mechanisms. The exact pathophysiology of AD has not been completely understood, and there are no curative therapies yet. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol that is noted for its antioxidant and anti-inflammatory properties. Objective: To review the role of resveratrol in the pathophysiological aspects of AD. Methods: This study carried out a literature review using PubMed/Medline, Virtual Health Library (VHL), Web of Sciences, SCOPUS and the Cochrane Library databases. Original research articles, describing both in vitro and in vivo experiments, published between 2008 and 2018, were included. Results: We identified 667 articles, of which 619 were excluded because they were repeated or did not follow the inclusion criteria. The present study includes the remaining 48 articles. Discussion: Resveratrol demonstrates beneficial and protective effects in AD models and seems to provide a promising therapeutic alternative. Conclusion: Although resveratrol appears to mitigate some pathophysiological aspects of AD, further studies are needed to prove the safety and efficacy of this compound in humans.

RESUMO Introdução: A doença de Alzheimer (DA) é neurodegenerativa e caracterizada por perda progressiva e irreversível da função cognitiva. A presença de placas senis é um dos marcadores patológicos da doença e está associada ao aparecimento de mecanismos neuroinflamatórios. A fisiopatologia exata da DA ainda não é completamente compreendida, e ainda não existem terapias curativas. O resveratrol (3,5,4'-trihidroxi-trans-estilbeno) é um polifenol conhecido por suas propriedades antioxidantes e anti-inflamatórias. Objetivo: Revisar o papel do resveratrol nos aspectos fisiopatológicos da DA. Métodos: Este estudo realizou uma revisão narrativa da literatura a partir das bases de dados PubMed/Medline, Biblioteca Virtual em Saúde (BVS), Web of Science, SCOPUS e Cochrane Library. Foram incluídos artigos originais, realizados in vitro e in vivo, publicados entre 2008 e 2018. Resultados: Foram identificados 667 artigos, dos quais 619 foram excluídos por estarem repetidos ou não se enquadrarem nos critérios de inclusão. O presente estudo inclui os 48 artigos restantes. Discussão: O resveratrol demonstra efeitos benéficos e protetores em modelos de DA, bem como parece fornecer uma alternativa terapêutica promissora. Conclusão: Embora o resveratrol pareça atenuar alguns aspectos fisiopatológicos da DA, são necessários mais estudos para comprovar a segurança e a eficácia deste composto em seres humanos.

Informe diário de evidências COVID-19: busca realizada em 29 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 29, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 3 protocolos.

Inhibition of paracetamol-induced acute kidney damage in rats using a combination of resveratrol and quercetin / Inhibición de daño renal agudo inducido por paracetamol en ratas usando una combinación de resveratrol y quercetina

Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= - 0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.

La sobredosis de paracetamol (también llamado acetaminofen o APAP) causa un daño agudo en el hígado y los riñones, tanto en humanos como en modelos animales experimentales, a través de la inducción de la vía del estrés oxidativo. Intentamos determinar si los antioxidantes y los compuestos antiinflamatorios combinados, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal inducida por una dosis tóxica de APAP en un modelo de rata de lesión renal aguda inducida por APAP. Las ratas recibieron una dosis única de APAP (2 g / kg) antes de ser sacrificadas después de 24 horas o se trataron previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg), antes de ser tratadas, se administró una dosis única de APAP y luego fueron sacrificadas 24 horas después de la ingestión. Los tejidos renales recolectados se tiñeron con H-E y fueron observados a través de microscopía óptica. Las muestras de tejido se analizaron para (i) biomarcadores de estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (ii) biomarcadores de inflamación, factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6). Las imágenes teñidas con H & E mostraron que la sobredosis de APAP indujo daño renal agudo como lo demuestra la ampliación del espacio glomerular, la dilatación tubular, numerosos desechos celulares en los túbulos renales con degeneración epitelial tubular y la vacuolización, que se protegieron eficazmente con RES + QUR Se observó una protección parcial del espacio glomerular. Además, APAP modificó significativamente (p <0.05) los niveles tisulares de MDA, SOD, TNF-α e IL-6, que estaban protegidos por RES + QUR. Además, se observó una correlación positiva significativa (p <0,0001) entre el espacio glomerular y el TNF-α, (r = 0,8899), IL-6 (r = 0,8986) y MDA (r = 0,8552), mientras que la puntuación del espacio glomerular versus SOD mostró correlación negativa (r = - 0,7870). Concluimos que el resveratrol más quercetina protege sustancialmente contra la lesión renal aguda inducida por APAP en ratas, posiblemente a través del aumento de antioxidantes y la inhibición del estrés oxidativo y la inflamación.

Low-dose resveratrol supplementation on heart rate variability in hypertensive volunteers: a controlled double-blind trial / Suplementação de baixa dose de resveratrol na variabilidade da frequência cardíaca em hipertensos: ensaio clinico controlado e duplo cego

OBJECTIVE: Hypertension decreases the heart rate variability (HRV). Resveratrol, a phenolic compound found in grapes and their products, has been explored for its potential to treat hypertension. We evaluated the effects of low-dose resveratrol on HRV in hypertensive volunteers. METHOD: Twenty-one hypertensive volunteers of both sexes were supplemented with resveratrol (n = 11) or placebo (n = 10) for 30 days. HRV parameters were measured before and during a standardized treadmill exercise. One resveratrol- and 3 placebo-treated patients were lost to follow-up. RESULTS: There were no anthropometric differences between resveratrol (n = 10) and placebo (n = 7) other than a difference in body mass index. The measured HRV parameters did not differ between resveratrol and placebo, or between control and treadmill exercise. CONCLUSION: Low-dose resveratrol did not alter HRV in hypertensive patients.

OBJETIVO: A hipertensão arterial diminui a variabilidade da frequência cardíaca (VFC). Resveratrol têm sido estudado como tendo potencial para o tratamento da hipertensão. Foram avaliados os efeitos de baixas doses de resveratrol na variabilidade da frequência cardíaca em voluntários hipertensos. MÉTODO: Vinte e um voluntários hipertensos, de ambos os sexos foram suplementados com resveratrol (n = 11) ou placebo (n = 10) durante 30 dias. Parâmetros da VFC foram medidos antes e durante o exercício em esteira padronizado. Um paciente tratado com resveratrol e três tratados com placebo foram perdidos. RESULTADOS: Não houve diferenças antropométricas entre os integrantes dos grupos resveratrol (n = 10) vs. placebo (n = 7), exceto uma diferença de índice de massa corporal. Não foram observadas diferenças para nenhum dos parâmetros da VFC entre resveratrol vs. placebo, ou entre controle vs. exercício em esteira. CONCLUSÃO: A baixa dose de resveratrol não afetou a VFC em hipertensos.