Neuroprotective Potential of a Novel Soluble Guanylate Cyclase Stimulator the Riociguat Alone or in a Combination Manner with Resveratrol in Experimental Stroke Model in Rats / Potencial Neuroprotector del Novedoso Estimulador de Guanilato Ciclasa Soluble, el Riociguat solo o en Combinación con Resveratrol en un Modelo Experimental de Ataque Cerebrovascular en Ratas

SUMMARY: In this study we aimed to examine the effect of novel vasodilatory drug Riociguat co-administration along resveratrol to recover neurodegeneration in experimental stroke injury. For that purpose, thirty-five adult female rats were divided into five groups (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) of seven animals in each. Animals in Control group did not expose to any application during the experiment and sacrificed at the end of the study. Rats in the rest groups exposed to middle cerebral artery occlusion (MCAO) induced ischemic stroke. MCAO + R group received 30 mg/kg resveratrol, and MCAO + BAY group received 10 mg/kg Riociguat. The MCAO + C group received both drugs simultaneously. The drugs were administered just before the reperfusion, and the additional doses were administered 24h, and 48h hours of reperfusion. All animals in this study were sacrificed at the 72nd hour of experiment. Total brains were received for analysis. Results of this experiment indicated that MCAO led to severe injury in cerebral structure. Bax, IL-6 and IL-1ß tissue levels were up-regulated, but anti-apoptotic Bcl-2 immunoexpression was suppressed (p<0.05). In resveratrol and Riociguat treated animals, the neurodegenerations and apoptosis and inflammation associated protein expressions were improved compared to MCAO group, but the most success was obtained in combined treatment exposed animals in MCAO + C group. This study indicated that the novel soluble guanylate stimulator Riociguat is not only a potent neuroprotective drug in MCAO induced stroke, but also synergistic administration of Riociguat along with resveratrol have potential to increase the neuroprotective effect of resveratrol in experimental cerebral stroke exposed rats.

En este estudio, nuestro objetivo fue examinar el efecto de la coadministración del nuevo fármaco vasodilatador Riociguat junto con resveratrol para recuperar la neurodegeneración en lesiones por ataques cerebrovasculares experimentales. Para ello, se dividieron 35 ratas hembras adultas en cinco grupos (Control, MCAO, MCAO + R, MCAO + BAY, MCAO + C) de siete animales en cada uno. Los animales del grupo control no fueron sometidos a ninguna aplicación durante el experimento y se sacrificaron al final del estudio. Las ratas de los grupos expuestas a la oclusión de la arteria cerebral media (MCAO) indujeron un ataque cerebrovascular isquémico. El grupo MCAO + R recibió 30 mg/kg de resveratrol y el grupo MCAO + BAY recibió 10 mg/kg de Riociguat. El grupo MCAO + C recibió ambos fármacos simultáneamente. Los fármacos se administraron antes de la reperfusión y las dosis adicionales se administraron a las 24 y 48 horas de la reperfusión. Todos los animales en este estudio fueron sacrificados a las 72 horas del experimento. Se recibieron cerebros totales para su análisis. Los resultados indicaron que la MCAO provocaba lesiones graves en la estructura cerebral. Los niveles tisulares de Bax, IL-6 e IL- 1ß estaban regulados positivamente, pero se suprimió la inmunoexpresión antiapoptótica de Bcl-2 (p <0,05). En los animales tratados con resveratrol y Riociguat, las neurodegeneraciones y las expresiones de proteínas asociadas a la apoptosis y la inflamación mejoraron en comparación con el grupo MCAO, sin embargo el mayor éxito se obtuvo en el tratamiento combinado de animales expuestos en el grupo MCAO + C. Este estudio indicó que el nuevo estimulador de guanilato ciclasa soluble Riociguat no solo es un fármaco neuroprotector potente en el ataque cerebrovascular inducido por MCAO, sino que también la administración sinérgica de Riociguat junto con resveratrol tiene el potencial para aumentar el efecto neuroprotector del resveratrol en ratas experimentales expuestas a un ataque cerebrovascular.

Effective Inhibition of TNFalpha/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression / Inhibición Efectiva de la Inflamación Hepática Mediada por el Eje TNF-alfa/mTOR y la Fibrosis Inducida por TAA Utilizando una Combinación de Metformina y Resveratrol en Asociación con la Inhibición del Gen Profibrótico y la Expresión de Proteínas

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment / 口腔疾病防治

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats / 中国组织工程研究

BACKGROUND:Resveratrol is a natural antioxidant extracted from plants.Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation.In this study,the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis. OBJECTIVE:To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats. METHODS:After 1 week of adaptive training,male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group:blank control group,resveratrol group,exercise group,resveratrol + exercise group.Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise.After swimming with a weight of 5%for 1 hour every day,50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally,6 days a week,for a total of 6 weeks.Samples were collected 24 hours after the last exercise,and the levels of urea nitrogen,creatine kinase,blood glucose,liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit.The activity of phosphoenolpyruvate carboxykinase was detected by microassay,and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay.Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α. RESULTS AND CONCLUSION:In the exercise group,plasma urea nitrogen and creatine kinase levels of rats were significantly increased(both P<0.05),liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased(all P<0.01),and blood glucose and liver glycogen contents were significantly decreased(both P<0.01).Resveratrol supplementation could effectively improve the above conditions.Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase(P<0.01,P<0.05),and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue(P<0.01).The mRNA expression levels of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased(all P<0.01),while resveratrol supplementation could significantly increase the gene expression levels of this pathway.To conclude,resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise,and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway,improving rate-limiting enzyme activity,promoting liver gluconeogenesis,and increasing blood glucose and liver glycogen levels.

Action mechanism of resveratrol intervention on ventricular remodeling in exercise-induced fatigue rats / 中国组织工程研究

BACKGROUND:Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart,but its action mechanism needs further study. OBJECTIVE:To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats. METHODS:Totally 48 male Sprague-Dawley rats were randomly divided into four groups,with 12 rats in each group.Rats in the blank control group were fed conventionally.After one week of adaptive training,rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming(5%body mass lead block fixed in the tail,70%-80%maximal oxygen uptake intensity),6 days a week,60 minutes a day.Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol(50 mg/kg per day)by gavage one hour after exercise intervention.Blank control group and exercise-related fatigue group were given the same volume of 2%dimethyl sulfoxide,6 days a week,once a day for 6 weeks.The body mass and heart mass of the rats were measured 24 hours after the last intervention.Plasma creatine kinase isoenzyme,cardiac troponin 1,pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA.The mRNA expression levels of ventricular remodeling-related factor Foxp1,transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the blank control group,the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group(P＜0.05).Compared with the exercise-related fatigue group,the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group(P＜0.05).Compared with the blank control group,the levels of creatine kinase isoenzyme,cardiac troponin 1 and uncoupling protein 1 increased(P＜0.01),and the level of pyruvate dehydrogenase decreased(P＜0.01)in the exercise-related fatigue group.Compared with the exercise-related fatigue group,the levels of creatine kinase isoenzyme,myocardial troponin 1 and uncoupling protein 1 decreased(P＜0.05),and the level of pyruvate dehydrogenase increased(P＜0.05)in the exercise-related fatigue with resveratrol supplement group.Compared with the blank control group,the expression of the Foxp1 gene decreased(P＜0.01),and the expression of transforming growth factor β1 and endothelin 1 gene increased(P＜0.01)in the myocardium of the exercise-related fatigue group.Compared with the exercise-related fatigue group,the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased(P＜0.01),while the expression of the transforming growth factor β1 and endothelin 1 gene decreased(P＜0.05).It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy.Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats.This effect may be related to the regulation of Foxp1/transforming growth factor β1/endothelin 1 signaling pathway.

Modulatory effect of resveratrol on oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis / 中国组织工程研究

BACKGROUND:Knee osteoarthritis is a common clinical degenerative joint disease characterized by chronic inflammation and oxidative stress.Resveratrol has anti-inflammatory and anti-oxidative stress biological effects,and therefore it can be used symptomatically and expected to provide a new strategy for the treatment of knee osteoarthritis. OBJECTIVE:To investigate the therapeutic effect and mechanism of resveratrol on knee osteoarthritis in rats through the silence information regulator 1(SIRT1)/forkhead transcription factor O1(FOXO1)pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into control group,model group,low-dose resveratrol group,and high-dose resveratrol group,with 10 rats in each group.Knee osteoarthritis models were established in the model group,low-dose resveratrol group,and high-dose resveratrol group.A mixture of 4%papain solution and 0.3 mol/L cysteine solution(1:1 for 0.5 hours;20 μL)was injected at 1,4,and 7 days after modeling.Rats in the low-dose and high-dose resveratrol groups were injected with 25 and 100 mg/kg resveratrol through the articular cavity at 1 day after successful modeling,while those in the control and model groups were injected with equivalent volume of physiological saline through the articular cavity.After 28 days of treatment,the maximum knee joint activity was measured;the levels of oxidative stress indicators and inflammatory factors in the synovial fluid of the knee joint were analyzed by radioimmunoassay and ELISA;the content of collagen fibers in the knee joint was analyzed by safranin O-fast green staining;the degree of arthritic lesions was analyzed using the Mankin histological score;and the levels of SIRT1 and FOXO1 in the knee joint were detected by western blot assay. RESULTS AND CONCLUSION:Compared with the model group,the maximum knee flexion and extension angles of rats significantly increased in the low-dose and high-dose resveratrol groups,and were significantly higher in the high-dose group than the low-dose group(P<0.05).Compared with the model group,the levels of superoxide dismutase and glutathione peroxidase in the knee joint fluid of rats significantly increased in the low-dose and high-dose resveratrol groups.The level of malondialdehyde significantly decreased in both resveratrol groups,and the level in the high-dose resveratrol group was significantly better than that in the low-dose resveratrol group(P<0.05).Compared with the model group,the low-dose and high-dose resveratrol groups showed a significant decrease in the levels of interleukin 1β,interleukin 6 and tumor necrosis factor α in the knee joint fluid of rats,and the levels of these inflammatory factors were significantly lower in the high-dose resveratrol group than the low-dose resveratrol group(P<0.05).Compared with the model group,the content of collagen fibers in the knee joint was significantly increased in both resveratrol groups,and the high-dose resveratrol group showed a higher content of collagen fibers than the low-dose resveratrol group(P<0.05).Compared with the model group,the expression level of SIRT1 in the knee joints of rats significantly increased in both resveratrol groups,while the level of acetylated FOXO1 significantly decreased(P<0.05).The magnitude of changes was significantly better in the high-dose group than the low-dose group.To conclude,resveratrol significantly improves the levels of oxidative stress and inflammatory factors in the joint fluid of rats with knee osteoarthritis and alleviates arthritic symptoms in a dose-dependent manner,possibly through the SIRT1/FOXO1 pathway.

Research on the role of resveratrol against breast cancer / 中国药房

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

Research on the role of resveratrol against breast cancer / 中国药房

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Influence of resveratrol on apoptosis in knee osteoarthritis rats by regulating autophagy mediated by SIRT1/AMPK signaling pathway / 中国免疫学杂志

Objective:To investigate the effect of resveratrol on apoptosis of chondrocytes in rats with knee osteoarthritis(KOA)through autophagy mediated by silent information regulator 1(SIRT1)/adenylate activated protein kinase(AMPK)signaling pathway.Methods:Fifty healthy Wistar rats were randomly separated into control group,model group,resveratrol group,resveratrol+ SIRT1 inhibitor group,and autophagy activator group,with 10 rats per group.Except for the control group,the other rats were injected with Freund's complete adjuvant to establish the KOA rat model,resveratrol group,resveratrol+AMPK inhibitor group,and autophagy activator group were treated with 10 μmol/kg resveratrol,10 μmol/kg resveratrol+10 mg/kg EX527,2 mg/kg rapamycin,respectively.After 4 weeks,the grade of Lequesne MG knee joint of rats were observed;the levels of IL-6 and tumor necrosis factor-β(TNF-β)in rat knee joint fluid were measured;HE staining and TUNEL staining were used to observe the morphology and apoptosis of rat knee cartilage;transmission electron microscope was used to observe the autophagy in rat chondrocytes;Western blot was performed to determine the protein expressions of SIRT1,p-AMPK,AMPK,LC3 and Beclin-1.Results:Compared with control group,the local reaction,gait reaction,joint activity,and joint swelling of model group were increased;compared with model group,the local response,gait response(P<0.05),joint activity,and joint swelling in resveratrol group and autophagy activator group were reduced(P<0.05).Compared with control group,the cartilage tissue cells in model group were disordered and rough,with fibrotic degeneration,marginal humeral bulge,reduced organelles,and vacuolar degeneration,the number of autophagosomes was increased,the levels of IL-6 and TNF-β in knee joint fluid,chondrocyte apoptosis rate,Beclin-1 and LC3B/A were increased(P<0.05),the SIRT1 and p-AMPK/AMPK in cartilage tissue were decreased(P<0.05);compared with model group,resveratrol group and autophagy activator group showed improvement in the disordered arrangement of cartilage tissue cells and the marginal humeral bulge,the number of autophago-somes was increased,the levels of IL-6 and TNF-β in knee joint fluid,and the apoptosis rate of chondrocytes were decreased(P<0.05),the levels of SIRT1,p-AMPK/AMPK,Beclin-1 and LC3B/A in cartilage tissue were increased(P<0.05);SIRT1 inhibitor could reverse the protective effect of resveratrol group on rat chondrocytes.Conclusion:Resveratrol maybe autophagic KOA rat chon-drocyte apoptosis mediated by activating SIRT1/AMPK pathway,which can be reversed by SIRT1 inhibitor.

Neuroprotective effects of the combined treatment of resveratrol and urapidil in experimental cerebral ischemia-reperfusion injury in rats

ABSTRACT Purpose: To evaluate the neuroprotective effect of resveratrol, urapidil, and a combined administration of these drugs against middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (IR) injury model in rats. Methods: Thirty-five rats were divided into five groups of seven animals each. Animals in IR, IR resveratrol (IRr), IR urapidil (IRu), and IR + combination of resveratrol and urapidil (IRc) were exposed to MCAO induced cerebral ischemia reperfusion injury model. Rats in IRr and IRu groups received 30-mg/kg resveratrol and 5-mg/kg urapidil respectively. Animals in IRc received a combined treatment of both drugs. At the end of the study, brain tissues were used for oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), pro-apoptotic caspase-3, anti-apoptotic Bcl-2, and pro-inflammatory tumor necrosis factor-α cytokine level measurements. Results: The MCAO model successfully replicated IR injury with significant histopathological changes, elevated tissue oxidative stress, and upregulated apoptotic and inflammatory protein expression in IR group compared to control group (p < 0.001). All parameters were significantly alleviated in IRr group compared to IR group (all p < 0.05). In IRu group, all parameters except for caspase-3 and Bcl-2 were also significantly different than IR group (all p < 0.05). The IRc group showed the biggest difference compared to IR group in all parameters (all p < 0.001). The IRc had higher superoxide dismutase and Bcl-2 levels, and lower caspase-3 levels compared to both IRr and IRu groups (all p < 0.05). Also, the IRc group had lower MDA and TNF-α levels compared to IRu group (all p < 0.05). Conclusions: The results indicate that combined treatment of resveratrol and urapidil may be a novel strategy to downregulate neurodegeneration in cerebral IR injury.

Quantitative and qualitative analysis of neuroinflammation by beta amyloid1-42 toxin after treatment with resveratrol-loaded nanoparticles / Análise quantitativa e qualitativa da neuroinflamação pela toxina beta amilóide1-42 após tratamento com nanopartículas de resveratrol

Background: This study evaluated the effects of zein nanoparticles with resveratrol on neuroinflammation caused by Alzheimer's disease. Method: The sample consisted of 30 animals divided into control (C), positive control (CP), white nanoparticles (NB), resveratrol nanoparticles (NR) and resveratrol (R) groups. The animals received 10 mg/kg of resveratrol or nanoparticles according to the group, daily, for 15 days, oral administration. Afterward, they were submitted to immunohistochemical (IHC) analyses. Results: the IHC showed that there was no change in the morphological brain composition in the NR and C groups. Conversely, in the CP, NB, and R groups, changes in the deposition of Anti Tau were observed. The NR group showed a normal projection of taurine in the axon, which was not presented in the same way in the other groups. The CD68 marker showed no microglial activation in the R and C groups. Quantitative analyses of Anti Beta-Amyloid in the NR group showed a statistical difference com-pared to the CP, NB, and R groups, whereas the Anti Tau analysis showed a significant difference between the CP and NR groups. The CD68 marker showed a significant difference between the C and NR groups. The analysis of cy-tokines showed a significant difference in TNF-α between the C and CP groups, C and NB groups, CP and NR groups, and NB and NR groups. IL-6 and InF-δ showed no significant difference between all groups. IL-10 showed significant differences between the C and NR groups, C and R groups, and CP and NR groups. Conclusion: NR prevented the evolution of neuroinflammation(AU).

Introdução: Este estudo avaliou os efeitos das nanopartículas de zeína com resveratrol na neuroinflamação causada pela doença de Alzheimer. Método: A amostra consistiu em 30 animais divididos em grupos de controle (C), controle positivo (CP), nanopartículas brancas (NB), nanopartículas de resveratrol (NR) e resveratrol (R). Os animais receberam 10 mg/kg de resveratrol ou nanopartículas de acordo com o grupo, diariamente, por 15 dias, por via oral. Em seguida, foram submetidos a análises imuno-histoquímicas (IHC). Resultados: A IHC mostrou que não houve alteração na composição morfológica do cérebro nos grupos NR e C. Por outro lado, nos grupos CP, NB e R, foram observadas alterações na deposição de Anti Tau. O grupo NR mostrou uma projeção normal de taurina no axônio, que não se apresentou da mesma forma nos outros grupos. O marcador CD68 não mostrou ativação microglial nos grupos R e C. As análises quantitativas do antibeta-amiloide no grupo NR mostraram uma diferença estatística quando comparadas aos grupos CP, NB e R, enquanto a análise do antitau mostrou uma diferença significativa entre os grupos CP e NR. O marcador CD68 mostrou uma diferença significativa entre os grupos C e NR. A análise das citocinas mostrou uma diferença significativa no TNF-α entre os grupos C e CP, C e NB, CP e NR, e NB e NR. IL-6 e InF-δ não apresentaram diferença significativa entre todos os grupos. A IL-10 apresentou diferenças significativas entre os grupos C e NR, C e R, e CP e NR. Conclusão: A NR impediu a evolução da neuroinflamação (AU).

Autophagic-Related anticancer effect of grapes extract and tomatoes extract: Ex-Vivo study

Cells undergo autophagy to save themselves from injury, but progressive autophagy can cause cell death. This study characterized and compared the effect of grape (resveratrol) and tomato (lycopene) extracts and their combination on modulating autophagy-related miRNA and its target gene in squamous cell carcinoma cell line. Docking analysis for extracts and selected genes was performed. Methyl Thiazol Tetrazolium assays were used to assess the cytotoxicity of extracts and their combination toward HEp-2 cells. qRT-PCR was used to quantify changes in gene expression. Data were statistically analyzed. miRNA-20a was identified as a potential effector in laryngeal cancer, and sequestosome-1 (SQSTM1) was its target gene. Docking analysis showed that resveratrol interacted with miRNA-20a and showed less affinity toward SQSTM1. Hydrogen bonds and hydrophobic interactions were predicted. In contrast, lycopene showed less affinity toward miRNA-20a than resveratrol. Increasing doses of resveratrol, lycopene, and their combination induced a statistically significant reduction in mean percent viability and mean fold changes of miRNA-20a and SQSTM1 expression in treated HEp-2 cells. Pearson's correlation showed a statistically significant positive correlation between miRNA-20a and SQSTM1 (R=0.812, p≤0.001). Grape and tomato extracts and their combination display promising cytotoxicity against HEp-2 cells in a dose- and time-dependent fashion. Both extracts reduce the expression of miRNA-20a and SQSTM1 with subsequent inhibition autophagy and promotion of apoptosis in HEp-2 cells.

Las células se someten a autofagia para salvarse de lesiones, pero la autofagia progresiva puede provocar la muerte celular. Este estudio caracterizó y comparó el efecto de los extractos de uva (resveratrol) y tomate (licopeno) y su combinación en la modulación de miARN relacionado con la autofagia y su gen diana en la línea celular de carcinoma de células escamosas. Se realizó análisis de acoplamiento para extractos y genes seleccionados. Se utilizaron ensayos de metil tiazol tetrazolio para evaluar la citotoxicidad de los extractos y su combinación frente a las células HEp-2. qRT-PCR se utilizó para cuantificar los cambios en la expresión génica. Los datos fueron analizados estadísticamente. El miARN-20a se identificó como un efector potencial en el cáncer de laringe y el secuenciasoma-1 (SQSTM1) fue su gen diana. El análisis de acoplamiento mostró que el resveratrol interactuaba con miRNA-20a y mostraba menos afinidad hacia SQSTM1. Se predijeron enlaces de hidrógeno e interacciones hidrofóbicas. Por el contrario, el licopeno mostró menos afinidad hacia el miARN-20a que el resveratrol. El aumento de las dosis de resveratrol, licopeno y su combinación indujo una reducción estadísticamente significativa en el porcentaje medio de viabilidad y los cambios medios en la expresión de miRNA- 20a y SQSTM1 en las células HEp-2 tratadas. La correlación de Pearson mostró una correlación positiva estadísticamente significativa entre miRNA-20a y SQSTM1 (R=0,812, p≤0,001). Los extractos de uva y tomate y su combinación muestran una citotoxicidad prometedora contra las células HEp-2 de forma dependiente de la dosis y el tiempo. Ambos extractos reducen la expresión de miRNA-20a y SQSTM1 con la posterior inhibición de la autofagia y promoción de la apoptosis en células HEp-2.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer / 中国中药杂志

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.

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.

Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of Male Hypogonadism / 中国结合医学杂志

OBJECTIVE@#To determine whether resveratrol (Res) can correct osteoporosis induced in a rat model of male hypogonadism.@*METHODS@#Thirty-two rats were randomly divided into 4 groups, 8 in each group; 1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy (ORCD) without ligation of any arteries or veins or removal of the testis and epididymis; 2) a control + Res-treated group (Con+Res): underwent sham surgery similar to the control, but was then treated with Res, as described below; 3) an ORCD-induced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density (BMD) and bone mineral content (BMC) were measured in the tibia and femur of each rat's right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline (Dpd), N-telopeptide of type I collagen (NTX I), alkaline phosphatase (ALP), and osteocalcin (OC), as well as receptor activator of nuclear factor kappa B (RANK) and osteoprotegerin (OPG) were assessed.@*RESULTS@#ORCD significantly decreased BMD (P<0.01) and significantly increased bone resorption, manifested by increased RANK. In addition, it inhibited serum levels of OPG and OC. Res treatment after ORCD effectively increased serum levels of bone formation markers such as OPG and OC, compared with testisectomized rats (P<0.05).@*CONCLUSION@#Res could ameliorate bone loss induced by male hypogonadism, possible via restoration of the normal balance between RANK and OPG.

Mechanism of resveratrol regulating ovarian cancer cell apoptosis by inhibiting HMGB1 / 中华内分泌外科杂志

Objective:To investigate the effect of resveratrol on apoptosis of ovarian cancer cells and its molecular mechanism, and to find a potential new target for the treatment of ovarian cancer.Methods:Ovarian cancer SKOV-3 cells were divided into control group and resveratrol group.The survival rate of SKOV-3 cells treated with resveratrol was measured by MTT assay. 24 h after resveratrol intervention in SKOV-3 cells, Western blot was used to detect the expression of Bcl-2, Bax, Caspase-3, HMGB1, TLR4 and NF-?B. Ovarian cancer SKOV-3 cells were transfected with si-NC, si-HMGB1, Rb1+pcDNA3.1 or Rb1+pcDNA3.1-HMGB1, and the sensitivity of cells to resveratrol was detected by MTT assay. The transfected cells were treated with resveratrol and apoptosis was detected by flow cytometry.Results:Resveratrol could inhibit the growth of ovarian cancer SKOV-3 cells, and the higher the concentration of resveratrol, the more significant the inhibitory effect. The expression level of HMGB1 in control cells and resveratrol group was 1.24±0.15 and 0.86±0.11, respectively. 25μM resveratrol inhibited HMGB1 protein level ( P<0.01) . The sensitivity to resveratrol was increased after HMGB1 was downregulated, and the apoptosis of SKOV-3 cells was promoted. HMGB1 overexpression increased the resistance to resveratrol and inhibited the apoptosis of SKOV-3 cells. TLR4 expression quantity control and resveratrol cells were 0.98±0.12 and 0.63±0.08, amount of NF-?B expression were 1.21±0.14 and 0.45±0.07, 25 μM resveratrol could cut TLR4 and NF-?B protein levels. Conclusions:Resveratrol can promote apoptosis of ovarian cancer SKOV-3 cells. This mechanism may be related to the down-regulation of HMGB1/TLR4/NF-?B, which provides a basis for resveratrol treatment of ovarian cancer.

Preventive and therapeutic effects of resveratrol on lens opacification in diabetic rats and its mechanism / 中华实验眼科杂志

Objective:To investigate the preventive and therapeutic effects of resveratrol on lens opacification in diabetic rats and its biological mechanism.Methods:Fifty 8-week-old healthy male SPF grade SD rats were selected and randomly divided into blank control group, model group, gliclazide group, low-dose resveratrol group and high-dose resveratrol group according to their body weight, with 10 rats in each group.The diabetes model was established by intraperitoneal injection of streptozotocin in model group, gliclazide group, low-dose resveratrol group and high-dose resveratrol group.On the third day after modeling, rats in gliclazide group was gavaged with 2 mg/(kg·d) gliclazide suspension, and rats in low-dose and high-dose resveratrol groups were gavaged with 20 and 40 mg/(kg·d) resveratrol, respectively, for four weeks.Rats in blank control group and model group were gavaged with the same volume of normal saline once a day, also for four weeks.After the diabetes model was established, there were 10 rats in blank control group and 9 rats in the other four groups.The fasting blood glucose concentration of the rats was measured with a blood glucose meter.The concentrations of fasting insulin, superoxide dismutase (SOD) 1, SOD2, SOD3, and glutathione peroxidase (GPX1) were determined by enzyme-linked immunosorbent assay.Lens opacification after treatment was observed by slit lamp microscopy.Morphologic changes in lens cells were examined by hematoxylin-eosin staining.Apoptosis of lens epithelial cells (LECs) was detected using TUNEL.The relative expressions of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in lens tissues were determined by Western blot.The study protocol was approved by the Welfare Ethics Committee of Experimental Animal of Zhengzhou University (No.IACYC2019-02).Results:Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were increased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were decreased in model group in comparison with blank control group, and the differences were statistically significant (all at P<0.05). Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were decreased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were increased in gliclazide group, low-dose resveratrol group, and high-dose resveratrol group compared with model group, and the differences were statistically significant (all at P<0.05). Fasting blood glucose concentration, fasting insulin level, and apoptosis rate of LECs were decreased and the concentrations of SOD1, SOD2, SOD3, and GPX1 were increased in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, and the differences were statistically significant (all at P<0.05). The proportions of grade 0, 1 and 2 lens opacities after treatment were 100.00%, 0.00% and 0.00% in blank control group, 0.00%, 66.67% and 33.33% in model group, 77.78%, 22.22% and 0.00% in gliclazide group, 22.22%, 44.44% and 33.33% in low-dose resveratrol group, and 66.67%, 33.33% and 0.00% in high-dose resveratrol group, respectively, with a statistically significant difference ( H=7.514, P<0.001). Compared with model group, lens opacification was less severe in blank control group, gliclazide group, low-dose resveratrol group, and high-dose resveratrol group, with statistically significant differences (all at P<0.05). Lens opacification was less severe in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, showing statistically significant differences (both at P<0.05). Compared with model group, there were fewer abnormal changes of lens cells and sub-organelles in gliclazide group, low-dose resveratrol group and high-dose resveratrol group, and the abnormalities in gliclazide group and high-dose resveratrol group were slighter.Compared with model group, the relative expression levels of Nrf2 and HO-1 were higher in blank control group, gliclazide group, low-dose resveratrol group, and high-dose resveratrol group, with statistically significant differences (all at P<0.05). The relative expression levels of Nrf2 and HO-1 were higher in gliclazide group and high-dose resveratrol group compared with low-dose resveratrol group, showing statistically significant differences (both at P<0.05). Conclusions:Resveratrol can reduce lens opacification in diabetic rats and its mechanism may be related to the regulation of the Nrf2/HO-1 signaling pathway by exerting antioxidative stress effects.