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).

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.

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.

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.

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.

白藜芦醇对实验性自身免疫性心肌炎大鼠心肌巨噬细胞极化及心肌炎性损伤的影响

目的:探讨白藜芦醇(Res)对实验性自身免疫性心肌炎(EAM)大鼠心肌巨噬细胞极化及炎性损伤的影响。方法:建立EAM大鼠模型,分为对照组、EAM组、Resveratrol组,通过免疫荧光、HE染色观察心肌组织巨噬细胞浸润程度并对心肌病理损伤进行评分;采用Realtime PCR检测巨噬细胞极化标记分子诱生型一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)及炎症因子白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的表达变化,Western blot检测NLRP3炎性小体蛋白组分的表达变化。结果:EAM组大鼠心肌组织可见大量巨噬细胞浸润,伴有明显的心肌纤维断裂、溶解;IL-6、IL-1β、TNF-α、iNOS mRNA表达均较Control组显著增加(分别为P<0.05,P<0.05,P<0.01,P<0.01),而Arg1表达较Control组显著减少(P<0.05);Resveratrol可减少EAM大鼠心肌组织巨噬细胞浸润数量及心肌病理损伤积分(均P<0.05),减少IL-6、IL-1β、TNF-α、iNOS mRNA的表达(均P<0.05),增加Arg1的表达(P<0.01)。同时,与Control组比较,EAM大鼠心肌组织NLRP3和Caspase-p10、pro-Caspase-1及IL-1β蛋白表达明显升高(均P<0.05),Resveratrol可显著减少人NOD样受体家组蛋白3(NLRP3)、Caspase-p10、pro-Caspase-1及IL-1β蛋白表达,差异具有统计学意义(均P<0.05)。结论:巨噬细胞浸润并向M1型极化参与EAM大鼠心肌炎性损伤;Res可能通过抑制M1型巨噬细胞向M2型极化、NLRP3炎症小体激活及相关炎性因子释放减轻EAM心肌损伤。

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。

白藜芦醇激活细胞外信号调节激酶5信号蛋白促进小鼠MC3T3-E1细胞增殖

背景:细胞外信号调节激酶5信号蛋白对生物体的存活不可或缺,白藜芦醇能通过多种途径促进成骨细胞增殖,但其是否能通过细胞外信号调节激酶5信号蛋白调控成骨细胞功能还需进一步验证。目的:探究细胞外信号调节激酶5对MC3T3-E1细胞增殖以及相关分泌蛋白的调控作用,进一步验证白藜芦醇通过激活细胞外信号调节激酶5完成上述过程。方法:小鼠MC3T3-E1前成骨细胞分别用完全培养基、XMD8-92(细胞外信号调节激酶5抑制剂)、表皮生长因子(细胞外信号调节激酶5激活剂)和白藜芦醇单独干预及XMD8-92+表皮生长因子、白藜芦醇+XMD8-92干预后,通过Western blot检测各组细胞内细胞外信号调节激酶5、磷酸化细胞外信号调节激酶5蛋白,增殖相关蛋白Cyclin D1、CDK4、PCNA,以及成骨细胞分泌蛋白骨保护素、核因子κB受体活化因子配体的表达情况,使用细胞免疫荧光染色检测各组细胞外信号调节激酶5、骨保护素和核因子κB受体活化因子配体荧光强度,使用EdU染色检测各组细胞增殖情况。白藜芦醇干预MC3T3-E1细胞的适宜浓度及时间由细胞形态学观察和CCK-8实验确定。结果与结论:①细胞外信号调节激酶5信号蛋白的激活能有效促进MC3T3-E1细胞增殖、上调骨保护素/核因子κB受体活化因子配体比值;②白藜芦醇干预MC3T3-E1细胞的适宜浓度及时间为5μmol/L,24 h;③白藜芦醇可以激活细胞外信号调节激酶5信号蛋白,进而促进成骨细胞增殖,并上调骨保护素/核因子κB受体活化因子配体比值;④研究结果表明,白藜芦醇可以通过激活细胞外信号调节激酶5信号蛋白促进MC3T3-E1细胞增殖,并通过激活细胞外信号调节激酶5信号蛋白上调骨保护素/核因子κB受体活化因子配体比值。

Vaticanol(B,Cand G) ,α-Viniferin和Hopeaphenol体外抑制小鼠骨髓生成的肥大细胞介质释放(英文)

目的 :α viniferin ,vaticanol(B ,CandG)和hopeaphenol是白黎芦醇的低聚体 ,具有抗肿瘤和抗氧化等活性 ,而这些化学保护作用是与其抗炎作用有联系。本文研究旨在了解这些化合物对小鼠骨髓分化肥大细胞 (BMMC)组织胺、肿瘤坏死因子和白三烯介质释放的影响 ,并观察对细胞外信号调节激酶 (ERK)的激活作用。方法 :分离小鼠骨髓细胞 ,培养 4～ 5周 (RPMI 16 4 0 ,IL 310ng/ml) ,抗 DNPIgE致敏 ,以DNP BSA( 30ng/ml)刺激释放反应。在非免疫刺激释放实验中 ,A2 3187作为刺激剂。结果 :所试化合物均表现出不同程度的抑制BMMC释放反应的作用。这些化合物对IgE刺激的TNF α和LTs释放表现出显著的抑制作用 ,而对IgE刺激的组织胺释放反应 ,只有vaticanolB和vaticanolC具有抑制作用 ( 10 0μmol/L)。在A2 3187介导的非免疫刺激释放反应中 ,vaticanol(B ,C和G)和hopeaphenol对组织胺释放表现出明显的对抗作用 ,大多数所试化合物有效地抑制了TNF α和LTs的释放 ,唯vaticanolC和vaticanolG对LTs的释放无明显影响。α viniferin和vaticanolC有效地抑制了IgE刺激的ERK酶的激活。结论 :α viniferin ,vaticanol(B ,C和G)和hopeaphenol能有效地抑制肥大细胞的炎性介质的释放反应 。

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.

Resveratrol: A potential challenger against gastric cancer

Gastric cancer(GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor.Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori(H. pylori) arethe major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent.Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here.

Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats

The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin （65 mg kg-1）-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, p53 and forkhead transcription factor 0 3a （FOXO3a）, superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SI RT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.

Resveratrol Induces Apoptosis and Autophagy in T-cell Acute Lymphoblastic Leukemia Cells by Inhibiting Akt/mTOR and Activating p38-MAPK

Objective To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia （T-ALL） cells and potential molecular mechanisms. Methods The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTI- test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. Results Resveratrol inhibited the proliferation and dose and time-dependent manner. It also induced cyclin-dependent kinase （CDK） inhibitors p21 and induced apoptosis and autophagy in T-ALL cells in a cell cycle arrest at G0/G1 phase via up regulating p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins （Mcl-1 and Bcl-2） and increased the expression of proapoptotic proteins （Bax, Bim, and Bad）, and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-11/LC3-1 and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. Conclusion Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p7OS6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.

Effects of resveratrol and other polyphenols in hepatic steatosis

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis.Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health,and thus their study has become an increasingly important area of human nutrition research.The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts,on hepatocyte and liver fat accumulation under different steatosis-inducing conditions.The results reported clearly show that this group of biomolecules is able to reduce fat accumulation,but further studies are needed to establish the optimal dose and treatment period length.With regard to the potential mechanisms of action,there is a good consensus.The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis,increased in fatty acid oxidation,and reduced of oxidative stress and inflammation.As a general conclusion,it can be stated that polyphenols are biomolecules which produce hepatoprotective effects.To date,these beneficial effects have been demonstrated in cultured cells and animal models.Thus,studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice

AIM: To determine the therapeutic efficacy of resveratrol on ulcerative colitis (UC) and its underlying mechanisms. METHODS: The mouse UC model was developed using 5% dextran sulfate sodium. Mice were randomly divided into four groups: normal control, UC model group, resveratrol low-dose group (RLD; 50 mg/kg per day), and resveratrol high-dose group (RHD; 100 mg/kg per day). RESULTS: The results showed that RLD regulates Treg/Th17 balance mainly through reducing the number of Th17 cells, whereas RHD regulates Treg/Th17 balance through both downregulating the number of Th17 cells and upregulating the number of Treg cells. Resveratrol can also regulate the level of plasma and intestinal mucosal cytokines including interleukin (IL)-10, transforming growth factor-beta 1, IL-6, and IL-17. The expressions of hypoxia inducible factor (HIF)-1 alpha, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 were significantly decreased in the intestinal tissues of mice treated with resveratrol. CONCLUSION: The therapeutic efficacy of resveratrol in UC is dose dependent and closely associated with the regulation of Treg/Th17 balance and the HIF-1 alpha/mTOR signaling pathway.

Protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat

Objective:To study the protective effect of resveratrol on lens epithelial cell apoptosis in diabetic cataract rat.Methods:A total of 84 Wistar rats were divided into 4 groups:12 in Group A(control group).24 in Group B(diabetic cataract group),24 in Group C(therapeutic-dose of resveratrol group) and 24 in Group D(low-dose of resveratrol group).Rats in Group B-D were given with60 mg/kg streptozotocin through intraperitoneal injection.Rats in Group C were given with 100mg/kg resveratrol and rats in Group D were given with 20 mg/kg resveratrol.The caspase-3expression levels and apoptosis ratios of LEC among each group were observed:the degrees of lens opacity in Group B-D after 12 weeks were compared.Results:There were significant differences in caspase-3 expression levels,apoptosis ratios of T.F.C among groups at 4 w,8 w and12 w(P<0.05).After 12 weeks,in Group B the degree of lens opacity was as follow:0(0.00%) in grade Ⅰ,3(37.50%) in grade Ⅱ,2(25.00%)in grade Ⅲ,2(25.00%)grade Ⅳ,and 1(12.50%) in gradeⅤ:in Group C:2(25.00%)in grade Ⅰ,4(50.00%) in grade Ⅱ.2(25.00%)in grade Ⅲ,0(0.00%)gradeⅣ,and 0(0.00%) in grade Ⅴ;in Group D:1(12.50%)in grade Ⅰ,4(50.00%) in grade Ⅱ,2(25.00%)in grade Ⅲ,1(12.50%) grade Ⅳ,and 0(0.00%) in grade Ⅴ.The.difference among Group B-D was statistically significant(P<0.05).Conclusions:Resveratrol has protective effect on lens epithelial cell apoptosis in diabetic cataract rat,and the effect is relative to its dose.