Synergistic anticancer activity of resveratrol in combination with docetaxel in prostate carcinoma cells

BACKGROUND/OBJECTIVESThe study was conducted to investigate the efficacy of the combination treatment of phytochemical resveratrol and the anticancer drug docetaxel (DTX) on prostate carcinoma LNCaP cells, including factors related to detailed cell death mechanisms.MATERIALS/METHODSUsing 2-dimensional monolayer and 3-dimensional spheroid culture systems, we examined the effects of resveratrol and DTX on cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, apoptosis, and necroptosis by MTT, flow cytometry, and Western blotting.RESULTSAt concentrations not toxic to normal human prostate epithelial cells, resveratrol effectively decreased the viability of LNCaP cells depending on concentration and time. The combination treatment of resveratrol and DTX exhibited synergistic inhibitory effects on cell growth, demonstrated by an increase in the sub-G₀/G₁ peak, Annexin V-phycoerythrin positive cell fraction, ROS, mitochondrial dysfunction, and DNA damage response as well as concurrent activation of apoptosis and necroptosis. Apoptosis and necroptosis were rescued by pretreatment with ROS scavenger N-acetylcysteine.CONCLUSIONSWe report resveratrol as an adjuvant drug candidate for improving the outcome of treatment in DTX therapy. Although the underlying mechanisms of necroptosis should be investigated comprehensively, targeting apoptosis and necroptosis simultaneously in the treatment of cancer can be a useful strategy for the development of promising drug candidates.     

白藜芦醇抗骨质疏松的研究机制进展

骨质疏松是一种随着年龄增长或病态而骨质不断流失、骨微结构不断恶化且易致骨折的全身代谢性疾病。随着人口的老龄化,全世界的发病率都在持续上升,这严重的影响了老年人群的健康和生活质量。白藜芦醇具有雌激素样作用且在骨骼中具有多向靶点,能促进骨髓间充质干细胞成骨分化、增加成骨细胞增殖生长及抑制破骨细胞,白藜芦醇治疗骨质疏松的研究日益增多并有一定的进展。本文将对近年来白藜芦醇防治骨质疏松症的研究进展作一综述。     

白藜芦醇对去卵巢大鼠生殖系统的影响

目的观察白藜芦醇(RES)对去卵巢大鼠生殖系统的影响,研究其雌激素样作用。方法48只SD大鼠随机分为6组,分别为A组:假手术、B组:去卵巢、C组:去卵巢+0·03mg/(kg·bw)已烯雌酚(DES)、D、E、F组:去卵巢+RES(分别为5,15和45mg/(kg·bw)剂量组,处理90d,观察大鼠血清雌二醇浓度、动情周期、子宫指数及子宫内膜的变化。结果A组血清雌二醇浓度显著高于其余5组(P<0·05),子宫指数A组显著高于B、D、E、F组,C组显著高于A组(P<0·05);阴道涂片显示B组大鼠基本无动情期,C组大鼠动情期明显,D、E、F组大鼠部分出现动情期;D、E、F组子宫内膜部分萎缩变薄,内薄上皮细胞形态正常,C组大鼠子宫内膜无萎缩,内膜上皮细胞水肿,但无明显增生。结论白藜芦醇在去卵巢大巢体内有较弱的雌激素样作用,对大鼠子宫内膜无促进增生的副作用。     

Interaction between resveratrol and thrombin and its biological implication

In view of important implication of resveratrol and thrombin in the process of platelet aggregation and apoptosis, the interaction effect between them and its biological implication was studied. Resveratrol could decrease fluorescence emission intensities of thrombin by a dynamic collision quenching process. The binding process was spontaneous and the resveratrol–thrombin complex formation was an endothermal reaction induced by hydrophobic interaction and hydrogen. Non-radiation energy transfer occurred from thrombin to resveratrol at the molecular level. Kinetic studies showed that the fluorescence intensity of thrombin linearly decreased along with prolonged time, whereas resveratrol intensity reduced continuously with degressive plateau in the form of second exponential decay function. Moreover, the interaction caused a decrease of α-helical structure resulting in thrombin conformation alteration. In addition, the isomerization of resveratrol was not prevented but its stability was improved with the addition of thrombin. This work might give deeper insight into resveratrol as a kind of nutritional factor with the inhibition of platelet aggregation and stimulation of platelet apoptosis in the functional food.     

Protective effect of resveratrol on arsenic trioxide-induced nephrotoxicity in rats

BACKGROUD/OBEJECTIVES

Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide (As₂O₃)-induced Male Wistar rats.

MATERIALS/METHODS

Adult rats received 3 mg/kg As₂O₃ (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before As₂O₃ treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed.

RESULTS

Rats treated with As₂O₃ had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content (0.805 ± 0.059 µg/g) of kidneys in rats treated with As₂O₃. However, resveratrol had no effect on zinc level in the kidney relative to As₂O₃-treated groups.

CONCLUSIONS

Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.     

白藜芦醇对高脂模型小鼠脂代谢影响

目的探讨白藜芦醇对高脂模型小鼠脂代谢影响。方法 50只雄性小鼠随机分为基础对照组,高脂组,白藜芦醇低、中、高剂量组;除基础对照组外,其他组均喂饲高脂饲料,4周后白藜芦醇低、中、高剂量组分别给予白藜芦醇5,22,45 mg/kg灌胃,共干预6周,检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)和高密度脂蛋白-胆固醇(HDL-C)。结果不同剂量白藜芦醇干预6周即显现出降低高脂模型小鼠血脂水平的趋势或作用,以中剂量组作用最明显,TC、TG和LDL-C分别为(3.174±0.687)、(0.884±0.408)和(1.762±0.877)mmol/L,与高脂组比较,血清TG和LDL-C明显下降(P<0.05);白藜芦醇还具有减轻高脂模型小鼠肝脏脂肪变性的作用。结论白藜芦醇干预对高脂模型小鼠可产生降脂作用。     

白藜芦醇对大鼠肾氧化损伤保护作用

目的 探讨白藜芦醇对高糖高脂饮食大鼠肾氧化损伤的保护作用。方法 大鼠分为正常对照组、高糖高脂组、白藜芦醇低、中、高剂量组,13周后处死大鼠,测定血糖血脂、肾组织氧化应激水平、抗氧化酶活性及肾脏过氧化物酶激活受体α(PPARα)、羟甲基戊二酸单酰辅酶A合成酶(HMGCS2)mRNA表达水平。结果 高糖高脂饮食13周后,高糖高脂组大鼠体重为(453.00±19.54)g,明显高于正常对照组(368.75±25.24)g和高剂量白藜芦醇组(400.40±30.39)g(t=4.545、2.991,P<0.05);高糖高脂组大鼠肾脏总抗氧化能力(T-AOC)、超氧化物歧化酶(T-SOD)分别为(1.22±0.34)、(2.69±0.13)U/(mg.Pro),明显低于正常对照组的(0.27±0.03)、(2.43±0.07)U/(mg.pro)(t=3.491,P=0.003;t=2.793,P=0.011)。结论 高糖高脂饮食大鼠肾内处于明显的氧化应激状态,白藜芦醇对高糖高脂饮食引起的氧化性肾损伤有保护作用。     

Effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats

BACKGROUND/OBJECTIVESHyperuricemic nephropathy is a common cause of acute kidney injury. Resveratrol can ameliorate kidney injury, but the explicit mechanism remains unclear. We investigated the effects of resveratrol on the inflammatory response and renal injury in hyperuricemic rats.MATERIALS/METHODSA rat model of hyperuricemic nephropathy was established by the oral administration of a mixture of adenine and potassium oxinate. Biochemical analysis and hematoxylin and eosin staining were performed to assess the rat kidney function. Enzyme-linked immunosorbent assays were performed to evaluate the immune and oxidative responses.RESULTSThe expression levels of urine albumin and β2-microglobulin were significantly decreased after resveratrol treatment. In addition, the levels of serum creatinine and uric acid were significantly decreased in the resveratrol groups, compared with the control group. The levels of proinflammatory factors, such as interleukin-1β and tumor necrosis factor-α, in kidney tissue and serum were also increased in the hyperuricemic rats, and resveratrol treatment inhibited their expression. Moreover, the total antioxidant capacity in kidney tissue as well as the superoxide dismutase and xanthine oxidase levels in serum were all decreased by resveratrol treatment.CONCLUSIONSResveratrol may protect against hyperuricemic nephropathy through regulating the inflammatory response.     

白藜芦醇对C57BL/6J小鼠脂代谢的影响

目的观察22.5mg/kg BW白藜芦醇对C57BL/6J小鼠血清和肝脏脂质的影响。方法 30只C57BL/6J雄性小鼠随机分为正常对照组、高脂组和高脂+白藜芦醇组,每组10只,正常对照组喂饲基础饲料,高脂组和高脂+白藜芦醇组喂饲高脂高胆固醇饲料。高脂+白藜芦醇组每日经灌胃给予22.5mg/kg BW白藜芦醇羧甲基纤维素钠溶液进行干预,正常对照组和高脂组均给予0.5%的羧甲基纤维素钠溶液灌胃。干预8周后测定小鼠血清TC、TG、HDL-C和LDL-C水平,肝脏TC和TG水平,并观察小鼠肝组织病理改变。结果高脂组和高脂+白藜芦醇组小鼠血清TC、LDL-C和HDL-C水平均高于正常对照组(P<0.05),高脂组血清TC和LDL-C水平还高于高脂+白藜芦醇组(P<0.05),但高脂组和高脂+白藜芦醇组小鼠血清TG水平均低于正常对照组(P<0.05)。高脂组小鼠肝脏TC水平高于高脂+白藜芦醇组和正常对照组(P<0.05)。结论 22.5mg/kg BW白藜芦醇可以降低喂饲高脂饲料的C57BL/6J小鼠体内胆固醇水平。     

白藜芦醇对高糖诱导系膜细胞增殖抑制作用

目的 研究白藜芦醇对高糖条件下系膜细胞增殖的影响,为白藜芦醇治疗糖尿病肾病提供实验依据。方法 体外培养大鼠系膜细胞,分为5组:对照组、高糖组、白藜芦醇2.5、5、10μmmol/L组;应用细胞计数Kit8(CCK8)法测定细胞增殖,流式细胞仪检测细胞周期和细胞凋亡。结果 高糖组细胞增殖率为(105.74±1.78)%,较对照组增高(P<0.01);白藜芦醇组细胞增殖率分别为(101.38±3.62)%、(96.55±1.28)%、(91.95±2.40)%,较高糖组减低(P<0.05或P<0.01);高糖组G1期细胞比例(62.86±1.57)%较对照组(57.93±2.70)%增高(P<0.05),白藜芦醇组G1期细胞比例较高糖组减少,其中10μmmol/L组与高糖组比较差异有统计学意义(P<0.05);高糖组S期细胞比例(29.00±1.08)%较对照组(34.91±1.43)%减少(P<0.01),白藜芦醇组S期细胞比例较高糖组增高,其中5、10μmmol/L组与高糖组比较差异有统计学意义(P<0.01);白藜芦醇5、10μmmol/L组细胞凋亡率分别为(2.20±0.53)%、(4.53±0.31)%,明显高于高糖组(P<0.01)。结论 白藜芦醇能抑制高糖诱导的系膜细胞增殖;白藜芦醇抑制增殖与影响细胞周期及诱导凋亡有关。     

白藜芦醇对铅诱导小鼠脂质过氧化的拮抗作用

目的探讨白藜芦醇对铅暴露引起的氧化损伤的拮抗作用。方法铅染毒动物模型用含铅(醋酸铅0.5%)饮用水构建。60只健康雄性昆明种小鼠随机分为6组,每组10只:正常对照组,铅染毒组,铅染毒+白藜芦醇低、中、高剂量干预组,白藜芦醇组。检测小鼠血铅和组织铅含量及肝、肾组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性和丙二醛(MDA)的含量和抗氧化能力指数。结果与铅染毒组相比,白藜芦醇处理组肝、肾组织中SOD、CAT和GSH-Px活性均上升(P<0.01),MDA含量降低(P<0.01)。白藜芦醇使用剂量在800～1 200mg/kg时能够显著地提高机体抗氧化酶的活力,增强机体的抗氧化能力。铅染毒小鼠血浆、肝组织及肾组织中ORAC值均有一定程度的减小,给予白藜芦醇可以拮抗铅毒性引起的ORAC值的下降。结论白藜芦醇通过提高抗氧化酶活性,以减轻铅毒引起的脂质过氧化损伤,提高小鼠机体的抗氧化能力,而实现保护肝、肾组织的作用。     

我国医疗机构药品集中采购工作回顾性研究

我国医疗机构药品集中采购工作迄今已经基本建立起以政府主导、省（区、市）为单位的集中采购模式,但控制药品价格、建立完善集中采购体系方面仍然需要加强。为实现进一步降低药品价格,政府试以降税为契机,实现终端销售价格明显下降。本研究通过了解全国各省抗癌药省级专项集中采购工作情况,对各省采购实施方案进行对比分析,了解当前各省抗癌药省级专项采购现状,为进一步完善我国抗癌药省级专项集中采购工作提供参考和建议。     

A novel red grape cells complex: health effects and bioavailability of natural resveratrol

In this study, we present a novel product consisted of red grape cells (RGC) grown in culture and evaluated its effect on human LDL oxidation (in vitro) and inflammatory stress (in an in vivo rat model). We analyzed RGC for its polyphenols content and characterized RGC-derived resveratrol (RES) and its properties; and finally, we characterized the pharmacokinetic profile of RGC-RES in human plasma. RGC has demonstrated a strong inhibitory effect on LDL oxidation with IC₅₀ as low as 8.0?μg/ml. RGC significantly reduced rats inflamed paw size induced by carrageenan injection. LC/MS analysis has shown that the main polyphenol in RGC was RES with one hexose moiety. The human pharmacokinetic analysis (clinicaltrials.gov NCT01747252) revealed relatively high bioavailability and two distinctly separated plasma concentration peaks at 1 and 5?h. The present study demonstrates antioxidant and anti-inflammatory traits of RGC that warrants further research in both pre-clinical and clinical settings.     

白藜芦醇对小鼠脂代谢及相关蛋白表达影响

目的探讨白藜芦醇（RSV）对高脂饲料喂养的C57BL/6J小鼠脂代谢及肝脏沉默信息调节因子1（SIRT1）及肝X受体α（LXRα）表达影响。方法雄性C57BL/6J小鼠30只,分为对照组、高脂组和RSV干预组（n=10）,对照组和高脂组分别喂饲基础饲料和高脂饲料,RSV干预组在喂饲高脂饲料同时给予RSV灌胃,第16周测定血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）含量,分离小鼠肝脏,测定TG、TC含量以及SIRT1、LXRα蛋白表达水平。结果与对照组比较,高脂组小鼠血清TG、TC、LDL-C含量[分别为（1.25±0.25）、（4.29±0.59）、（1.59±0.20）mmol/L]和肝脏TG、TC含量[分别为（5.78±1.69）、（2.69±1.20）mmol/L]升高,肝脏SIRT1、LXRα蛋白表达水平[分别为（0.36±0.03）、（0.78±0.07）]下降（P<0.05）;与高脂组比较,RSV干预组小鼠血清TG、TC、LDL-C含量[分别为（0.91±0.15）、（3.65±0.36）、（1.39±0.11）mmol/L]和肝脏TG、TC含量[分别为（4.63±1.70）、（1.65±0.89）mmol/L]明显下降,肝脏SIRT1、LXRα蛋白表达水平[分别为（0.41±0.05）、（0.88±0.09）]明显升高（P<0.05）。结论白藜芦醇可有效改善高脂饲料喂养C57BL/6J小鼠脂代谢异常,其机制可能与促进肝脏SIRT1及LXRα表达有关。     

白藜芦醇对心肌缺血再灌注损伤的保护作用及机制研究

目的研究白藜芦醇对大鼠心肌缺血再灌注损伤的保护作用,并进一步阐明其机制。方法建立心肌缺血再灌注损伤模型,持续观察标准Ⅱ导联心电图变化,测定乳酸脱氢酶(LDH),丙二醛(MDA)及超氧化物歧化酶(SOD)含量,确定心肌损伤程度。心肌细胞凋亡的检测采用逆转录聚合酶链反应检测bcl-2和bax mRNA的表达;Western blot检测bcl-2和bax蛋白表达。结果白藜芦醇能降低大鼠心肌冠脉结扎后ST段抬高,降低LDH和MDA水平,升高SOD水平,抑制bax而增强bcl-2的表达,减少心肌细胞凋亡。结论白藜芦醇对冠脉结扎诱发的大鼠心肌缺血再灌注损伤有保护作用,其机制可能与上调bcl-2蛋白表达,下调bax蛋白表达抑制心肌细胞凋亡有关。     

白藜芦醇联合大豆异黄酮对衰老模型大鼠学习记忆能力及葡萄糖转运蛋白表达的影响

目的探讨白藜芦醇联合大豆异黄酮干预对衰老模型大鼠回避记忆能力及海马组织神经元特异性核蛋白(neuron-specific nuclear protein, NeuN)阳性细胞数、葡萄糖转运蛋白(glucose transporter, GLUT)1及GLUT3基因和蛋白表达的影响。方法 60只SD雌性大鼠按体重随机分为6组:假手术组、衰老模型组、80 mg/kg白藜芦醇组、160 mg/kg大豆异黄酮组、80 mg/kg白藜芦醇+160 mg/kg大豆异黄酮组、0.8 mg/kg戊酸雌二醇阳性对照组。采用去卵巢合并腹腔注射100 mg/kg D-半乳糖制备衰老模型。干预组灌胃给予受试物,每天1次,持续12周。穿梭箱实验检测大鼠主、被动回避能力,免疫荧光染色检测NeuN阳性细胞数,实时荧光定量PCR和免疫印迹法分别检测海马GLUT1、GLUT3基因及蛋白水平。结果与假手术组相比,模型组大鼠回避潜伏时间延长,主动回避反应率及总回避反应率降低,NeuN阳性细胞数减少,GLUT1和GLUT3基因及蛋白表达水平下调(P<0.05)。与模型组相比,3个干预组大鼠回避潜伏时间明显缩短(P<...     

白藜芦醇对力竭运动大鼠心肌细胞凋亡影响

目的 摘探讨白藜芦醇对力竭运动大鼠心肌细胞氧化应激、凋亡影响及机制。方法 成年雄性SD大鼠随机分为5组：对照组、力竭运动组、白藜芦醇50、100、200 mg/kg组,检测大鼠心肌组织缺血缺氧面积、心肌组织超氧化物歧化酶（SOD）、丙二醛、Ca²⁺-ATPase含量,TUNEL法检测心肌细胞凋亡率,Western blot法检测心肌细胞Bax和caspase-3蛋白表达。结果 与对照组比较,力竭运动组大鼠心肌缺血缺氧面积[（112.27±48.27）μm²]与心肌组织丙二醛含量[（3.98±0.75）nmol/mgpro]明显升高、心肌组织SOD活性[（30.54±4.29）U/mgpro]与Ca²⁺-ATPase活性[（0.32±0.03）mol/（mg·h）]明显下降、心肌细胞凋亡指数[（23.4±2.3）%]与心肌组织Bax、caspase-3蛋白表达[（1.28±0.32）、（1.59±0.12）]明显升高;与力竭运动组比较,200 mg/kg白藜芦醇组大鼠心肌缺血缺氧面积[（22.12±10.22）μm²]与心肌组织丙二醛含量[（1.65±0.11）nmol/mgpro]明显减少、心肌组织SOD、Ca²⁺-ATPase活性[分别为（69.57±9.02）U/mgpro、（0.72±0.11）mol/（mg·h）]明显升高、心肌细胞凋亡指数[（10.4±1.3）%]与心肌组织Bax、caspase-3蛋白表达[（0.36±0.11）、（0.62±0.13）]明显降低（P<0.01）;呈明显剂量效应关系。结论 白藜芦醇可有效缓解大鼠力竭运动所致氧化应激状态,其机制可能与降低心肌组织Bax、caspase-3表达水平,减少心肌细胞凋亡有关。     

Dietary polyphenols and obesity

The prevalence of overweight and obesity and their associated metabolic disorders are considered a major threat to the public's health. While several diet and exercise programs are available for weight loss and prevention of weight regain, progress is often slow and disappointing. Recently, natural bioactive phytochemicals present in foods have been discovered for their potential health benefit effects on the prevention of chronic disorders such as cancer, cardiovascular disease, inflammatory and metabolic diseases including obesity. Polyphenols are a class of naturally-occurring phytochemicals, of which some such as catechins, anthocynines, resveratrol and curcumin have been shown to modulate physiological and molecular pathways that are involved in energy metabolism, adiposity, and obesity. The potential in vivo, beneficial effects of these polyphenols on adiposity and obesity as complementary agents in the up-regulation of energy expenditure have emerged by investigating these compounds in cell cultures, animal models of obesity and in some human clinical and epidemiological studies. In this brief review, the efficacy of the above-named polyphenols and their potential efficacy to modulate obesity and some associated disorders are discussed.