Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

Resveratrol combats chronic diseases through enhancing mitochondrial quality

Resveratrol(RSV),as a functional food component extracted from natural plants,has been widely studied and recognized in preventing and treating various diseases,with major mechanisms including executing anti-inflammation and anti-oxidation functions,and improving mitochondrial quality.Chronic diseases as non-communicable diseases are mainly caused by multiple factors,such as physiological decline and dysfunction in the body,and have become a significant challenge on public health worldwide.It is worth noting that chronic diseases such as Alzheimer's disease(AD),Parkinson's disease(PD),muscle atrophy,cardiovascular disease,obesity,and cancer are accompanied by abnormal mitochondrial function.Therefore,targeted regulation of mitochondria may be a meaningful way to prevent and treat chronic diseases.Increasing evidence has confirmed that RSV is actively involved in regulating mitochondria,and it has become an essential consideration to prevent and treat chronic diseases through targeting mitochondria and improving corresponding functions.In this article,current studies on RSV to optimize mitochondrial quality for preventing and alleviating chronic disease are systematically summarized,which can provide a theoretical reference for the development of functional foods or drugs to combat chronic diseases.

Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated forms, and not as the aglycone parent form(Pasinetti et al.,2015).

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts

BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers

Resveratrol(RSV),the primary polyphenol found in grapes,has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines,including IL-1β,IL-6,IL-1ra and TNFα.Considering the close association between chronic inflammation and cancer development,RSV’s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation,proliferation,neovascularization,and migration.Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress.In addition to immunomodulation,RSV inhibits cancer development by expressing anti-oxidant effects,causing cell cycle arrest,stimulating the function of certain enzymes,and activating cell signaling pathways.The end outcome is one of the various forms of cell death,including apoptosis,pyroptosis,necroptosis,and more,as it has been observed in vitro.RSV has been shown to act against cancer in practically every organ,while its effects on colon cancer have been documented more frequently.It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol.The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV,with a particular emphasis on cancers of the digestive tract,as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression.CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation,migration,invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

Biological function of resveratrol and its application in animal production:a review

With the prohibition of antibiotics in feed,plant functional substances have been widely studied as feed additives.Resveratrol,a natural stilbene,and a non-flavonoid polyphenol found in plants,possesses antioxidant,anti-inflammatory,and metabolic regulatory features.Resveratrol generated intense scientific and public interest,primarily due to its widely reported ability to prevent cancer,delay aging and alleviate related metabolic diseases.Recently,resveratrol has been studied and applied as a feed additive in animal production.This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present,including pigs,poultry,and ruminants.In pigs,dietary resveratrol improved intestinal health,mitochondrial function,meat quality,and more.In poultry,studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects.There are few studies on dietary resveratrol in ruminants;however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep.It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.

Resveratrol alleviates oxidative stress induced by oxidized soybean oil and improves gut function via changing gut microbiota in weaned piglets

Background Oxidized soybean oil(OSO)has been shown to impair growth and exacerbate inflammation,leading to intestinal barrier injury in animals.Recent evidence suggests important roles for resveratrol(RES)in the promoting growth performance,antioxidant capacity,anti-inflammatory,and regulate intestinal barriers in animals.Therefore,The objectives of this study are to investigate the effects of dietary RES(purity 98%)supplementation on the growth performance,antioxidant capacity,inflammatory state,and intestinal function of weaned piglets challenged with OSO.Methods A total of 28 castrated weaned male piglets with a similar body weight of 10.197 replications per treatment and±0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 1 piglet per replicate.Treatments were arranged as a 2×2 factorial with oil type[3%fresh soybean oil(FSO)vs.3%OSO]and dietary RES(0vs.300 mg/kg).Results The results showed that relative to the FSO group,OSO stress tended to decrease the average daily feed intake(ADFI),and decreased the activity levels of lipase,villus/crypt ratio(VCR),the mRNA expression of FABP1,SOD2,IL-10 and ZO-1 in the jejunum,and SOD2,GPX1,occludin and ZO-1 in the colon,the levels of acetic acid in the colonic digesta,whereas up-regulated the mRNA expression of IL-1βand TNF-αin the jejunum(P<0.05).Moreover,dietary supplementation with RES increased ether extract(EE),the activity levels of sucrase,lipase,α-amylase,villus height(VH)and VCR,the mRNA expression of FABP1,SOD2,IL-10 and occludin in the jejunum,and FABP1,PPAR-γ,GPX1,occludin and ZO-1 in the colon,and the abundance of Firmicutes,acetic and propionic acid,but decreased the levels of D-lactic acid in the plasma,the abundance of Bacteroidetes in the colonic digesta of weaned piglets compared to the non-RES group(P<0.05).Meanwhile,in the interaction effect analysis,relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO increased the activity levels of trypsin,VH in the jejunum,the abundance of Actinobacteria,the levels of butyric acid of weaned piglets,but failed to influence the activity levels of trypsin and VH,Actinobacteria abundance,the levels of butyric acid when diets were supplemented with FSO(interaction,P<0.05).Relative to the OSO group,dietary RES supplementation in the diets supplemented with OSO decreased the activity levels of DAO in the plasma of weaned piglets but failed to influence the activity levels of DAO when diets were supplemented with FSO(interaction,P<0.05).Relative to the FSO group,dietary RES supplementation in the diets supplemented with FSO decreased the level of propionic acid,whereas RES supplementation failed to influence the level of propionic acid when the diet was supplemented with OSO(interaction,P<0.01).Conclusions Inclusion of OSO intensified inflammatory states and impaired the intestinal health characteristics of weaned piglets.Dietary RES supplementation improved the antioxidant capacity,anti-inflammatory activity,and intestinal morphology.Further studies showed that the protective effects of RES on gut health could be linked to the decreased abundance of Prevotella_1,Clostridium_sensu_stricto_6,and Prevotellaceae_UCG003 and increased levels of acetic and propionic acid.

Protective effect of resveratrol against cadmium-induced toxicity on ovine oocyte in vitro maturation and fertilization

Background:Heavy metal cadmium(Cd)is a widespread environmental contaminant with a potential toxicity that might negatively affect female reproduction and fertility.It has been reported that Cd exposure impaired the quality of oocytes and led to a defective maturation and fertilization,through oxidative stress induction.Resveratrol(Res)is a natural polyphenol with strong antioxidant properties that exhibited protective role in preventing oocyte redox homeostasis disruption and quality decline.Here,we explored whether the addition of Res to in vitro maturation(IVM)medium might act as a protection against Cd-induced toxicity on ovine oocyte maturation and fertilization.Firstly,we evaluated the effect of supplementing IVM medium with two different Res concentrations(1and 2μmol/L)on nuclear maturation and fertilization of oocytes matured under CdCl2(2μmol/L)exposure.Therefore,the concentration of 1μmol/L Res was selected to analyse the effects of this compound on intracellular ROS levels,mitochondrial(mt)distribution and activity,chromatin configuration,cytoskeleton morphology,cortical granules(CGs)distribution and mRNA expression of genes associated with cellular response to oxidative stress(i.e.SIRT1,SOD 1,GPX1,GSR,CAT)in Cd-exposed in vitro matured oocytes.Results:We found that 1μmol/L Res restored the reduced oocyte meiotic competence induced by Cd exposure as well as,Res sustained oocyte ability to be normally fertilized and decreased polyspermic fertilization at both tested concentrations.Moreover,we demonstrated that 1μmol/L Res mitigated Cd-induced alterations of oocyte cytoplasmic maturation by reducing reactive oxygen species(ROS)accumulation,preventing mt dysfunction,maintaining the correct meiotic spindle and cortical F-actin assembly and the normal cortical granule distribution as well as up-regulating SIRT1,SOD1 and GPX1 genes.Conclusions:Taken together,our findings highlighted the beneficial influence exerted by Res in preventing Cdinduced disturbance of nuclear and cytoplasmic maturation and subsequent fertilization in ovine oocytes.Res treatment may help to establish defence strategies counteracting Cd-induced toxicity on the female gamete.

Effect of resveratrol in gestational diabetes mellitus and its complications

The incidence rate of diabetes in pregnancy is about 20%,and diabetes in pregnancy will have a long-term impact on the metabolic health of mothers and their offspring.Mothers may have elevated blood glucose,which may lead to blood pressure disease,kidney disease,decreased resistance and secondary infection during pregnancy.The offspring may suffer from abnormal embryonic development,intrauterine growth restriction,obesity,autism,and other adverse consequences.Resveratrol(RSV)is a natural polyphenol compound,which is found in more than 70 plant species and their products,such as Polygonum cuspidatum,seeds of grapes,peanuts,blueberries,bilberries,and cranberries.Previous studies have shown that RSV has a potential beneficial effect on complex pregnancy,including improving the indicators of diabetes and pregnancy diabetes syndrome.This article has reviewed the molecular targets and signaling pathways of RSV,including AMP-activated protein kinase,mitogen-activated protein kinases,silent information regulator sirtuin 1,miR-23a-3p,reactive oxygen species,potassium channels and CX3C chemokine ligand 1,and the effect of RSV on gestational diabetes mellitus(GDM)and its complications.RSV improves the indicators of GDM by improving glucose metabolism and insulin tolerance,regulating blood lipids and plasma adipokines,and modulating embryonic oxidative stress and apoptosis.Furthermore,RSV can ameliorate the GDM complications by reducing oxidative stress,reducing the effects on placentation,reducing the adverse effects on embryonic development,reducing offspring's healthy risk,and so on.Thus,this review is of great significance for providing more options and possibilities for further research on medication of gestational diabetes.

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet agerelated macular degeneration

AIM:To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration(AMD).METHODS:Fifty naïve and previously untreated patients suffering from wet AMD,were randomly assigned in two subgroups of 25 patients each.All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept(IAIs)followed by injections“according to need”,while in one group the patients also received daily two tablets of resveratrol oral supplement.Prior to treatment initiation,a complete ophthalmological examination,including best corrected visual acuity(BCVA)and contrast sensitivity evaluation,optical coherence tomography(OCT)scans,fundus autofluorescence(FAF),fluorescein angiography,indocyanine green angiography,and OCT angiography(OCTA),was performed to every participant,while all of them completed the Hospital Anxiety and Depression Scale(HADS)questionnaire,in order to assess their quality of life(QoL)status.The patients were assessed monthly for 1y with FAF,and OCT or OCTA;the main endpoints were the number IAIs,the changes in BCVA,in contrast sensitivity,and in patients’QoL status.RESULTS:No significant differences were present between the groups regarding the baseline demographic and clinical data.Over the 12-month period,a similar number of IAIs was applied in both groups(4.52±1.00 vs 4.28±0.90,P=0.38),while the rest of the clinical data also did not differ significantly after the completion of the study period.However,for HADS Depression(11.88±2.51 vs 8.28±1.54,P<0.001)and HADS Anxiety(11.92±2.52 vs 7.76±1.51,P<0.001)questionnaires values,the score was significantly better in patients who received resveratrol supplements.Moreover,a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity(0.17±0.19 vs 0.35±0.24,P=0.005),HADS Depression(0.08±1.38 vs-3.88±1.48,P<0.001),and HADS Anxiety(0.36±1.98 vs-5.12±2.70,P<0.001)scores,in favour of the patients treated with resveratrol supplements.CONCLUSION:The resveratrol oral supplement is a complementary treatment in cases of wet AMD,highlighting its effectiveness in improving patients’QoL status.

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis

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.vulnificusinduced 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 as an epigenetic therapy for flavivirus infection:A narrative review

Flaviviruses are a group of positive-stranded RNA viruses that cause a broad spectrum of severe illnesses in humans worldwide.Clinical manifestations of flavivirus infections range from mild febrile illness to hemorrhage,shock,and neurological manifestations.Flavivirus infections cause a substantial global health impact,with an estimated more than 400 million cases of infections annually.Hence,an understanding of flavivirus-host interaction is urgently needed for new antiviral therapeutic strategies.In recent years,many aspects concerning epigenetic therapy for viral infections have been addressed,including methylation of the genome,acetylation/deacetylation of histone complex and microRNA regulation.In this context,we surveyed and reviewed the literature and summarized the epigenetic effects of resveratrol,a natural polyphenol with potential anti-viral properties,on flavivirus infections.

Preparation of adhesive resveratrol micelles and determination of drug content

Objective:Resveratrol polymer micelles with tissue adhesion were prepared and the content of resveratrol in the micelles was determined by HPLC.Method:The micelle adhesion experiment was carried out by polylysine orifice plate experiment and small animal fluorescence imaging method,and the micelle prescription was optimized to obtain resveratrol micelles with good adhesion.The separation was performed on a Shiseido SPOLAR C18 column(150 mm×4.6 mm,5μm)with methanol-water(42:58)as the mobile phase.The flow rate was 1.0 mL·min^(-1),the detection wavelength was 305 nm,the column temperature was 35℃,and the injection volume was 10μL.Results:Resveratrol micelles prepared with F127 alone had the best adhesion.The peak area and concentration of resveratrol had a good linear relationship in the concentration range of 10~200μg/mL(r=0.9996).The specificity,precision,recovery and stability all met the methodological requirements.Conclusion:In this experiment,resveratrol micelles with tissue adhesion were successfully prepared,and a method for the determination of resveratrol content in micelles was established.The method is accurate,rapid and simple.

Synthesis of Resveratrol and Resveratrol Trinicotinate

Aim To synthesize a new prodrug, resveratrol trinicotinate. Methods Inpresence of lithium and a catalytic amount of naphthalene, the reaction of p-methoxybenzyltrimethylsilyl ether and 3,5-dimethoxylbenzaldehyde gave resveratrol after a series of translation.Resveratrol trinicotinate was obtained by the reaction of resveratrol and nicotinoyl chloridehydrochloride. Results A mutual prodrug resveratrol trinicotinate was designed and synthesized.Conclusion A novel method for synthesis of resveratrol and resveratrol trinicotinate has beenafforded. The E-isomer is selectivily obtained by dehydration of the compound 2 with KHSO_4 .

Resveratrol对糖尿病大鼠肾皮质4E-BP1和S6磷酸化表达的影响

目的:探讨Resveratrol对糖尿病(DM)大鼠早期肾脏肥大的影响及其可能的机制。方法:雄性SD大鼠13只,应用链脲佐菌素诱导建立DM大鼠模型,6只正常SD大鼠作为对照(NC)。DM大鼠于第11周随机分为DM组7只和Resveratrol(DR)组6只,DR组给予Resveratrol 10 mg/(kg.d)灌胃,共4周。第14周收集3组大鼠24 h尿测尿微量白蛋白。处死大鼠,心脏取血测血肌酐。取肾组织,制石蜡切片做HE染色,免疫组化观察肾皮质4E-BP1磷酸化蛋白表达量的变化。Western blot检测肾皮质S6磷酸化蛋白表达的改变。结果:与NC组相比,DR和DM组大鼠血糖、24 h尿微量白蛋白和血肌酐明显升高,而体重明显降低(P均<0.01),而用Resveratrol干预后DR组大鼠血糖、24 h尿微量白蛋白及血肌酐比DM组明显好转(P<0.05)。肾脏HE染色结果显示,DM组大鼠肾小球系膜基质中度增生,系膜细胞增生,系膜区明显扩大,肾小球体积增大。DR组肾小球系膜细胞和基质增生及肾小球系膜区扩张较DM组明显减轻。肾皮质免疫组化结果显示,4E-BP1磷酸化蛋白在DM组表达呈强阳性,在DR组表达呈弱阳性。DM和DR组大鼠血管组织中S6磷酸化蛋白的表达明显高于NC组(P<0.01),而DR组明显低于DM组(P<0.01)。结论:DM大鼠早期存在肾脏肥大和mTOR信号通路下游的4E-BP1和S6磷酸化蛋白表达增高。Resveratrol可能通过抑制4E-BP1和S6的磷酸化来减轻DM大鼠早期肾脏肥大,延缓糖尿病肾病的发展。

Research Progress of Mechanism of Action of Resveratrol

Resveratrol is a kind of polyphenolic compound that widely exists in plants and has extensive physiological pharmacological function and is very useful for human health. For the mechanism of action and function of RV, people are doing a variety of groundbreaking researches. Results show that the molecular mechanism of RV is embodied in aspects such as oxidative stress and diseases of neuropathy, anti-oxygenation and pro-oxidant effect and RV target molecule, etc. This article mainly summarized the mechanism of action of resveratrol in these aspects.

Resveratrol对高糖所致大鼠肾小球系膜细胞TGF-β1表达的影响

目的:探讨高糖对大鼠肾小球系膜细胞TGF-β1表达的影响及Resveratrol的干预作用。方法:体外培养大鼠肾小球系膜细胞。①分为正常对照组(NC组,葡萄糖浓度5.6mmol/L)、高糖组(HG组,葡萄糖浓度30mmol/L),分别观察24、48、72h;②分为NC组、HG组、Resveratrol组(Res组,葡萄糖浓度5.6mmol/L+Resveratrol20μmol/L)和高糖+Resveratrol组(HG+Res组,葡萄糖浓度30mmol/L+Resveratrol浓度分别为5、10、15、20μmol/L),各组细胞分别培养48h。用半定量RT-PCR和Western blotting法检测细胞内TGF-β1mRNA和蛋白表达变化。结果:①与NC组相比,HG刺激后大鼠系膜细胞TGF-β1mRNA和蛋白表达明显增加,差异均有显著性,P值均<0.01;②与HG组相比,HG+Resveratrol干预后,大鼠系膜细胞TGF-β1mRNA和蛋白表达呈浓度依赖性减少,差异均有显著性(P值分别为<0.05,<0.01)。Res组和NC组之间TGF-β1mRNA和蛋白表达的差异无显著性(P>0.05)。结论:高糖能上调大鼠肾小球系膜细胞TGF-β1mRNA和蛋白表达,Resveratrol可能通过抑制高糖引起的系膜细胞TGF-β1高表达而在糖尿病肾病中起治疗作用。

Resveratrol对高糖培养大鼠肾小球系膜细胞氧化应激和p27蛋白表达的影响

目的:探讨Resveratrol对高糖培养大鼠肾小球系膜细胞氧化应激和p27蛋白表达的影响。方法:体外培养大鼠肾小球系膜细胞,分为正常对照组(NC组,葡萄糖浓度5.6 mmol/L)、Resveratrol组(Res组,葡萄糖浓度5.6 mmol/L+Resveratrol 20μmol/L)、高糖组(HG组,葡萄糖浓度30mmol/L)和高糖+Resveratrol组(HG+Res组,葡萄糖浓度30 mmol/L+Resveratrol 20μmol/L),各组细胞分别培养72 h,用比色法测定细胞上清液丙二醛(malondialdehyde,MDA)含量,流式细胞仪检测细胞内活性氧(reactive oxygenspecies,ROS)含量,蛋白含量/细胞数比值评估系膜细胞大小,Western blot法检测细胞内p27蛋白表达的变化。结果:①与NC组相比,HG刺激后大鼠肾小球系膜细胞内MDA、ROS含量均明显上调(P<0.01);与HG组相比,HG+Resveratrol干预后大鼠肾小球系膜细胞内MDA、ROS含量均降低(P<0.05)。②与NC组相比,HG刺激72 h后,大鼠肾小球系膜细胞肥大、p27蛋白表达明显增加(P<0.01);与HG组相比,HG+Resveratrol干预后大鼠肾小球系膜细胞细胞肥大减轻、p27蛋白表达减少(P<0.05)。Res组和NC组之间p27蛋白表达无统计学意义(P>0.05)。结论:Resveratrol可能通过缓解高糖诱导系膜细胞的氧化应激、抑制p27蛋白高表达,减轻糖尿病肾脏疾病早期的肾脏肥大。

Dietary resveratrol improves antioxidant status of sows and piglets and regulates antioxidant gene expression in placenta by Keap1-Nrf2 pathway and Sirt1

Background: Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta.Methods: Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol. Oxidative stress biomarkers and antioxidant enzymes were measured in the placenta, milk, and plasma of sows and piglets. Antioxidant gene expression and protein expression of Kelch-like ECH-associated protein 1-Nuclear factor E2-related factor 2(Keap1-Nrf2), nuclear factor kappa B-p65(NFκB-p65) and sirtuin1(Sirt1) were quantified in the placenta.Results: Dietary resveratrol increased the litter and piglets weaning weights. Antioxidant status in the milk, placenta and plasma of sows and piglets was partially improved by dietary resveratrol. In placenta, Nrf2 protein expression was increased and Keap1 protein expression was decreased by dietary resveratrol. The m RNA expression of antioxidant genes including catalase(CAT), glutathione peroxidase 1(GPX1), GPX4, superoxide dismutase 1(SOD1)and heme oxygenase 1(HO1), and phase 2 detoxification genes, including glutamate-cysteine ligase modifier(GCLM), microsomal glutathione S-transferase 1(MGST1) and UDP glucuronosyltransferase family 1 member A1(UGT1 A1), was increased by dietary resveratrol. Dietary resveratrol also increased Sirt1 and phosphorylated NFκB-p65 protein expression in the placenta. We failed to observe any influences of dietary resveratrol on pro-inflammatory cytokine levels, including those of interleukin 1β(IL-1β), IL-6, IL-8 and tumor necrosis factor α(TNF-α). However, we observed that the m RNA expression of IL-8 in placenta was reduced by maternal resveratrol. In addition, dietary resveratrol showed interactive effects with day of lactation on activities of SOD and CAT and levels of malonaldehyde(MDA) and hydrogen peroxide(H2 O2) in milk.Conclusions: Dietary resveratrol supplementation during pregnancy and lactation improves the antioxidant status of sows and piglets, which is beneficial to the reproductive performance of sows. Dietary resveratrol regulates placental antioxidant gene expression by the Keap1-Nrf2 pathway and Sirt1 in placenta.