Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8

Resveratrol is a polyphenol that is mainly found in grapes and red wine and has been reported to be a caloric restriction (CR) mimetic driven by Sirtuin 1 (SIRT1) activation. Resveratrol increases metabolic rate, insulin sensitivity, mitochondrial biogenesis and physical endurance, and reduces fat accumulation in mice. In addition, resveratrol may be a powerful agent to prevent age-associated neurodegeneration and to improve cognitive deficits in Alzheimer’s disease (AD). Moreover, different findings support the view that longevity in mice could be promoted by CR. In this study, we examined the role of dietary resveratrol in SAMP8 mice, a model of age-related AD. We found that resveratrol supplements increased mean life expectancy and maximal life span in SAMP8 and in their control, the related strain SAMR1. In addition, we examined the resveratrol-mediated neuroprotective effects on several specific hallmarks of AD. We found that long-term dietary resveratrol activates AMPK pathways and pro-survival routes such as SIRT1 in vivo. It also reduces cognitive impairment and has a neuroprotective role, decreasing the amyloid burden and reducing tau hyperphosphorylation.     

Sulfation of resveratrol in human liver: Evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1

Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with anticancer and cardioprotective activities, was studied in human liver cytosol. In the presence of 3′-phosphoadenosine-5′-phosphosulfate, three metabolites (M1–3) whose structures were identified by mass spectrometry and NMR as trans-resveratrol-3-O-sulfate, trans-resveratrol-4′-O-sulfate, and trans-resveratrol-3-O-4′-O-disulfate, respectively. The kinetics of M1 formation in human liver cytosol exhibited an pattern of substrate inhibition with a K_i of 21.3?±?8.73?µM and a V_max/K_m of 1.63?±?0.41?µL?min^?1mg^?1 protein. Formation of M2 and M3 showed sigmoidal kinetics with about 56-fold higher V_max/K_m values for M3 than for M2 (2.23?±?0.14 and 0.04?±?0.01?µL?min^?1?mg^?1). Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. In conclusion, the results elucidate the enzymatic pathways of resveratrol in human liver, which must be considered in humans following oral uptake of dietary resveratrol.     

Resveratrol induces apoptosis and differentiation in acute promyelocytic leukemia (NB4) cells

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a naturally occurring phytoalexin found in grapes and wine, and has been reported to exert a variety of important pharmacological effects. We have investigated the activity of resveratrol on proliferation and differentiation of the acute promyelocytic leukemia cell line NB4. The growth inhibitory properties of resveratrol appear to be due to its induction of apoptotic cell death, as determined by morphological changes, DNA fragmentation, increased proportion of the subdiploid cell population and decreased mitochondrial transmembrane potential (Δψ_m). Colorimetric assay for activity of caspase-3 showed an obvious increase in caspase-3 activity in cells after treatment with resveratrol. However, the expression levels of protein Bcl-2 and Bax show no significant change in response to resveratrol treatment. These results suggest that apoptosis of NB4 cells induced by resveratrol requires caspase-3 activation and is related to the mitochondrial transmembrane potential. The combination of resveratrol and all-tran-retinoic acid (ATRA) induced 100% of the NB4 cells to become NBT-positive, whereas only a small part of cells became positive for NBT after a similar exposure to either resveratrol or ATRA alone. Thus, resveratrol may be useful in treating acute promyelocytic leukemia.     

白藜芦醇对小鼠移植宫颈癌生长及HIF-1α、VEGF表达的影响

目的 探讨白藜芦醇（Res）对小鼠宫颈癌细胞株U14移植瘤的抑制作用及其相关机制.方法 构建615近交系小鼠U14移植瘤动物模型,并随机分为对照组、Res组、顺铂组,每组10只,给予相应药物干预,接种后第26天处死全部小鼠,检测肿瘤体积及重量,计算抑瘤率,通过免疫组织化学染色法检测肿瘤组织微血管密度（MVD）,采用荧光实时定量PCR和Western blotting分析肿瘤组织缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）mRNA及蛋白表达水平.结果 Res组和顺铂组抑瘤率分别为50.46％、57.19％; Res组和顺铂组肿瘤体积、肿瘤质量较对照组显著降低（P＜0.01）;与对照组比较,Res组和顺铂组HIF-1α、VEGF mRNA与蛋白表达水平及MVD明显降低,差异有统计学意义（P＜O.01）,但Res组与顺铂组比较,差异无统计学意义（P＞0.05）.结论 Res通过下调HIF-1α、VEGF表达抑制小鼠宫颈癌的生长.     

葡萄废渣中活性物质提取工艺研究

目的：以酿酒工业废弃物葡萄废渣为材料,采用不同提取方法优化白藜芦醇、儿茶素提取工艺。方法：分别采用乙醇回流法、超声波法和闪式提取法对酿酒葡萄皮渣中的白藜芦醇、儿茶素进行提取,通过正交试验优化提取工艺。结果：超声波法提取率高于乙醇回流法和闪式提取法。超声波法提取葡萄废渣中白藜芦醇、儿茶素的最优工艺条件为乙醇浓度80%,料液比1∶10,提取时间30min。在此条件下白藜芦醇、儿茶素的提取总得率可达2.16%。结论：超声提取法适合于葡萄废渣中有效成分的提取,可在工业生产中推广使用。     

SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell death

Prion diseases associated with the conversion of the cellular prion protein (PrP(C)) to the misfolded isoform (PrP(Sc)), affect the central nervous system (CNS) of humans and animals. Resveratrol, an activator of class III histone deacetylase SIRT1, is important in attenuating cellular injury and oxidative stress. The present study investigated the effects of SIRT1 activation on prion protein-mediated neuronal cell death and examined its possible signals in intracellular apoptotic pathways. Resveratrol treatment significantly increased both SIRT1 protein expression and SIRT1 activity and protected neuronal cells against PrP (106-126)-induced cell death. Resveratrol-mediated SIRT1 activation decreased the acetylation of p53 and p65 induced by prion protein and SIRT1 inhibitor. SIRT1 activation also inhibited PrP (106-126)-mediated p38 mitogen-activating protein kinase (MAPK) activation and caspase-3 cleavage, and increased the expression of anti-apoptotic Bcl-xL protein. Furthermore, SIRT1 overexpression by using adenoviral vector protected neuronal cells against PrP (106-126). These results indicate that resveratrol inhibits PrP (106-126)-induced neuronal cell death by regulating SIRT1 activity and SIRT-related signaling, and suggest that prion-related disease may be attenuated by SIRT1 activation or by intake of SIRT1-activating molecules.     

白藜芦醇对去卵巢大鼠骨质疏松症的保护作用

Objective To investigate the protective effect and its mechanism of resveratrol (RES) on rats with osteoporosis. Methods A total of 72 clean grade female SD rats were randomly divided into six cohorts: control cohort, osteoporosis model cohort, estrogen pretreated cohort, low, median and high dosage RES pretreated cohorts. Except for rats in the control cohort, rats in other cohorts were treated by bilateral oophorectomy and pretreated with 17β-E2 and different dosage of resveratrol respectively, ranging from 1 to 12 weeks after operation. The blood parameters associating with osteoporosis were tested. Morphological observation of bone tissue was performed by HE staining under a microscope. Bone mineral density was measured by a dual-energy X-ray absorptiometry. The mRNA expression level of antioxidant enzymes (gpx1, trx1 and γ-gt) were assayed by RT-PCR. Results Serum calcium, serum phosphate, ALP and TRAP increased obviously, but estrogen and calcium level in serum decreased sharply in the animal model. The bone tissue of the model manifested typical osteoporosis characteristics, and the expression of antioxidant enzymes was at a low level. After treated with estrogen or different dosages of resveratrol, the parameters and phenotypes mentioned above were almost close to the control cohort.Conclusion Resveratrol, likely estrogen, can maintain a balance of bone formation and absorbance, which is critical to the homeostasis of bone, antagonizing the osteoporosis pathology progression. This protective mechanism is associated with the expression and activity of antioxidant     

白藜芦醇治疗2型糖尿病合并高血脂症的临床观察

目的观察白藜芦醇对2型糖尿病合并高血脂症患者的治疗效果。方法将观察病例随机分为2组,在常规治疗的基础上,治疗组给予白藜芦醇,对照组给予安慰剂,4周后检测血糖（FPG、2HPG）及血脂（TC、TG、HDL-C、LDL-C）指标。结果治疗组患者TC、TG、LDL-C明显下降（P〈0.05）,HDL-C明显升高（P〈0.05）,与对照组相比,有统计学意义（P〈0.05）;治疗组TC、TG下降（P〈0.05）,对照组TC、TG有升高趋势（P〉0.05）。结论白藜芦醇可以有效控制2型糖尿病合并高血脂症患者血脂水平,并能增强降糖药物的疗效。     

Impact of resveratrol supplementation on inflammatory,antioxidant, and periodontal markers in type 2 diabetic patients with chronic periodontitis

BackgroundDiabetes mellitus and periodontal disease are two common and chronic diseases with bidirectional relationship influence public health and quality of life. The aims of this study was to study the impact of resveratrol supplementation in adjunct with non-surgical periodontal therapy on inflammatory, antioxidant, and periodontal markers in patients with type 2 diabetes with periodontal disease.Materials and methodsIn this randomized clinical trial, 43 patients with diabetes and chronic periodontitis were randomly allocated into two intervention and control groups receiving either resveratrol supplements or placebo for 4 weeks. Serum levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), total antioxidant capacity (TAC) and clinical attachment loss (CAL) as the main index of periodontal marker were measured pre-intervention and post-intervention.ResultsIn the intervention group, the mean serum level of IL6 was reduced significantly (P = 0.039) post-intervention (2.19 ± 1.09 and 1.58 ± 1.06). No significant differences were seen in the mean levels of IL6, TNFα, TAC and CAL between two groups post-intervention.ConclusionsIt is suggested that daily consumption of resveratrol supplement may not change TNFα, TAC and CAL, but it would be beneficial in reducing serum levels of IL6. Therefore, further studies are suggested to investigate the effects of resveratrol supplementation along with NST on periodontal status.