Resveratrol inhibits the intracellular calcium increase and angiotensin/endothelin system activation induced by soluble uric acid in mesangial cells

Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca²⁺]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca²⁺]i. Pre-incubation with Resv significantly reduced the change in [Ca²⁺]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca²⁺]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.     

红葡萄酒及白藜三醇对血小板聚集的影响

观察红葡萄酒及其提取物白藜三醇对离体和在体条件下血小板聚集的影响 ,以探讨它们对心血管系统的保护作用机制。以高胆固醇饮食造成实验性高脂血症 ,以凝血酶、二磷酸腺苷和胶原为诱导剂 ,采用Born氏法测定血小板聚集率。结果发现 ,高脂饮食明显增加兔血浆胆固醇水平 ,并伴有血小板聚集的明显增强。同时给予红葡萄酒、去酒精红葡萄酒和白藜三醇可以消除高脂饮食对兔血小板聚集的增强作用。离体条件下白藜三醇明显抑制凝血酶、二磷酸腺苷及胶原诱导的健康人的血小板聚集。结果提示 ,红葡萄酒及白藜三醇均具有抑制血小板聚集的作用 ,此作用可能为白藜三醇抗动脉粥样硬化的机制之一。     

白藜芦醇对妊娠期糖尿病大鼠血糖及氧化应激影响的研究

目的：研究白藜芦醇（Resveratrol）对妊娠期糖尿病大鼠血糖及氧化应激水平的影响。方法：取100只妊娠5天的SD大鼠,通过一次性腹腔注射链脲佐菌素（Streptozotocin,STZ）35 mg?kg^-1制备大鼠糖尿病模型,随机分为6组：妊娠糖尿病模型对照组4组,各组白藜芦醇的注射量分别为30、60、120和240 mg?kg^-1,每组20只;正常妊娠对照组为20只妊娠5天SD大鼠;正常非妊娠对照组为20只非妊娠雌性大鼠。分别检测各组在第0、7、14天的空腹血浆血糖和胰岛素水平;治疗满2周后,检测各组大鼠血清中丙二醛（Malondialdehyde,MDA）、超氧化物歧化酶（Superoxide Dismutase,SOD）、谷胱甘肽过氧化物酶（Glutathione Peroxidase,GSH-Px）、过氧化氢酶（Catalase,CAT）的水平或活性。结果：与正常非妊娠对照组相比,正常妊娠对照组的大鼠空腹血浆血糖和胰岛素水平、血清中MDA 含量和SOD、GSH-Px、CAT活性均无显著性差异（P>0.05）;与妊娠期糖尿病模型组相比,白藜芦醇（30、60、120 和240 mg?kg^-1）治疗组大鼠血清中MDA含量显著降低（P<0.05,P<0.01）;白藜芦醇（120 和240 mg?kg^-1）治疗组大鼠血糖水平显著降低、胰岛素水平显著升高（P<0.05,P<0.01）,大鼠血清中SOD、GSH-Px、CAT活性显著升高（P<0.05,P<0.01）。结论：白藜芦醇对妊娠期糖尿病大鼠有降低血糖、提高抗氧化能力的作用,且具有剂量依赖性,该作用可能与其能够有效提高胰岛素水平和改善抗氧化酶系统的活性有关。     

白藜芦醇和有氧运动对高脂饮食大鼠血脂和血管内皮功能的作用

目的:探讨白藜芦醇以及有氧运动对高脂饮食大鼠血脂代谢、抗氧化及血管内皮功能的影响。方法:40只SD雄性大鼠随机分为正常饮食对照组(N组)、高脂饮食组(H组)、高脂饮食结合运动组(HE组)以及白藜芦醇和高脂饮食结合运动组(HER组),每组10只。运动组大鼠进行3天适应性无负重游泳30 min,以后隔日增加10 min,逐渐延长至90 min,并维持此量,每周训练5天,共8周。白藜芦醇组每天按50 mg/kg剂量灌喂白藜芦醇,其他组灌喂同剂量生理盐水。正常饮食组采用普通饲料,高脂饮食组采用高脂饲料。末次训练结束后,禁食8 h,乙醚麻醉,股动脉取血,肝素抗凝,制备血浆。检测反映血脂代谢的指标总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白AI(apoAI)、载脂蛋白B100(apoB100)和脂蛋白a[Lp(a)];反映抗氧化能力的指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)和氧化型低密度脂蛋白(OX-LDL)以及反映血管内皮功能的指标内皮素-1(ET-1)、降钙素基因相关肽(CGRP)和一氧化氮(NO)。结果:与N组比较,H组大鼠TC、LDL-C、OX-LDL、MDA、apoB100、Lp(a)、ET-1显著上升(P<0.05或P<0.01),而HDL-C、apoAI、SOD、CGRP、NO显著下降(P<0.05或P<0.01)。与H组比较,HE组大鼠TC、LDL-C、OX-LDL、MDA、apoB100、Lp(a)、ET-1显著降低(P<0.05或P<0.01),HDL-C、apoAI、SOD、CGRP、NO显著上升(P<0.05或P<0.01)。与HE组比较,HER组大鼠TC、LDL-C、OX-LDL、MDA、Lp(a)、ET-1呈下降趋势(P<0.05),HDL-C、apoAI、SOD、CGRP呈升高趋势(P<0.05)。结论:高脂饮食大鼠血脂紊乱,血管内皮功能下降,抗氧化能力明显减弱。有氧运动减轻高脂饮食大鼠血脂紊乱程度,提高血管内皮功能,增强机体抗氧化能力。有氧运动同时补充白藜芦醇的效果优于单纯运动。     

白藜芦醇抗肺部疾病作用的研究进展

白藜芦醇,属于多酚类化合物,已发现它具有抗氧化、抗肿瘤、抗炎、免疫调节、心血管保护等广泛的药理作用。越来越多的资料表明白藜芦醇还有防治肺部疾病的作用。就近年来白藜芦醇对肺部疾病如慢性阻塞性肺疾病、支气管哮喘、急性肺损伤、肺癌、肺动脉高压等的防治作用及可能机制的研究进展进行归纳、介绍和探讨,深入研究这些机制将为许多肺部疾病开辟新的治疗途径,为白藜芦醇的开发利用提供理论依据。     

白藜芦醇通过P53途径抑制H2O2诱导PC-12细胞凋亡

目的探讨白藜芦醇对H2O2引起的PC-12细胞损伤的保护作用与分子机制,为提高脑缺血神经损伤的疗效提供实验依据。方法用300μmol/L H2O2诱导处理PC-12细胞,建立神经元损伤模型,H2O2模型组未加入白藜芦醇处理,白藜芦醇处理组加入50μM白藜芦醇处理,2组均通过流式细胞术检测细胞凋亡,MTT法检测细胞活力,观察PC-12细胞形态的改变,Western blot检测细胞凋亡蛋白的表达及Sirt1-P53途径相关蛋白的表达,计数资料的分析采用χ2检验,计量资料的分析采用t检验,当P〈0.05时差异有统计学意义。结果成功建立了H2O2致PC-12细胞氧化应激损伤模型,白藜芦醇能够降低H2O2诱导的PC-12细胞凋亡率（H2O2模型组vs.白藜芦醇处理组=22.3%vs.8.1%,P〈0.05）,能够提高H2O2损伤的PC-12细胞的活力（24 h OD值：H2O2模型组vs.白藜芦醇处理组=0.45 vs.0.81,48 h OD值：H2O2模型组vs.白藜芦醇处理组=0.25 vs.0.71）,与H2O2组细胞形态相比,白藜芦醇组神经元的胞体较完整,大部分细胞存在少量的突起,细胞突起存在少量的联系;白藜芦醇通过下调凋亡蛋白Caspase3表达及上调Bcl-2表达,抑制PC-12细胞凋亡,进一步研究发现白藜芦醇是通过促进Sirt1表达量增加及P53去乙酰化发挥作用的。结论白藜芦醇对H2O2致PC-12细胞氧化应激损伤具有保护作用,这种保护功能是通过激活Sirt1从而促进P53去乙酰化起作用的。     

白藜芦醇对果蝇寿命影响及抗氧化机制研究

目的研究白藜芦醇对果蝇寿命的影响及其抗氧化机制。方法采用完全随机的方法将果蝇分为4组,比较不同浓度的白藜芦醇对果蝇寿命的影响,记录果蝇的平均寿命、最高平均寿命和半数死亡时间等指标;将100只健康小鼠按照随机数字表法分为空白对照组、溴代苯模型对照组、低剂量组、中剂量组和高剂量组,其中低、中及高剂量组分别予以不同浓度的白藜芦醇溶液连续灌胃30 d,测定血中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)的水平,取血后用溴代苯制造小鼠过氧化模型,然后测定肝脏GSH-Px、SOD、MDA水平。结果对照组、低、中、高剂量组果蝇的半数死亡时间分别为52、55、59及62 d;对照组、白藜芦醇低、中、高剂量组的寿命及最高寿命比较差异均有统计学意义(P<0.05);高剂量组白藜芦醇可显著增加正常小鼠及脂质过氧化模型小鼠GSH-Px和SOD的水平,显著降低MDA水平。结论白藜芦醇能剂量依赖性地延长果蝇寿命,其抗氧化作用可能是延长果蝇寿命的机制之一。     

Resveratrol,a phenolic antioxidant with effects on blood platelet functions

The main purpose of this article is to provide an overview of the currently available evidence of antiplatelet properties of resveratrol (3,4^′,5-trihydroxystilbene). Resveratrol, a phenolic compound found naturally in fruits, nuts, flowers, seeds and bark of different plants is integral part of human diet. It exhibits a wide range of biological effects, including antiplatelet, anti-inflammatory, anticancer, antimutagenic and antifungal properties. It is also a potent antioxidant, reactive oxygen species scavenger and metal chelators. Resveratrol reduces lipid peroxidation, oxidation and nitration of platelet and plasma proteins. This review article describes the chemical structure of resveratrol, its biological activity, the effects on blood platelet functions and the mechanisms involved in its action on blood platelets, the cells which play an important role not only in the haemostatic process, but also in pathogenesis of cardiovascular diseases.     

Inhibition of phosphatidylinositol 3-kinase-mediated glucose metabolism coincides with resveratrol-induced cell cycle arrest in human diffuse large B-cell lymphomas

An abnormally high rate of aerobic glycolysis is characteristic of many transformed cells. Here we report the polyphenolic compound, resveratrol, inhibited phosphatidylinositol 3-kinase (PI-3K) signaling and glucose metabolism, coinciding with cell-cycle arrest, in germinal center (GC)-like LY1 and LY18 human diffuse large B-cell lymphomas (DLBCLs). Specifically, resveratrol inhibited the phosphorylation of Akt, p70 S6K, and S6 ribosomal protein on activation residues. Biochemical analyses and nuclear magnetic resonance spectroscopy identified glycolysis as the primary glucose catabolic pathway in LY18 cells. Treatment with the glycolytic inhibitor 2-deoxy-D-glucose, resulted in accumulation of LY18 cells in G0/G1 -phase, underscoring the biological significance of glycolysis in growth. Glycolytic flux was inhibited by the PI-3K inhibitor LY294002, suggesting a requirement for PI-3K activity in glucose catabolism. Importantly, resveratrol treatment resulted in inhibition of glycolysis. Decreased glycolytic flux corresponded to a parallel reduction in the expression of several mRNAs encoding rate-limiting glycolytic enzymes. These results are the first to identify as a mechanism underlying resveratrol-induced growth arrest, the inhibition of glucose catabolism by the glycolytic pathway. Taken together, these results raise the possibility that inhibition of signaling and metabolic pathways that control glycolysis might be effective in therapy of DLBCLs.     

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.