白藜芦醇联合顺铂对神经胶质瘤细胞的作用*

目的： 探讨白藜芦醇联合顺铂对神经胶质瘤细胞C6 的作用。方法：不同浓度的白藜芦醇与顺铂单独联合 作用于神经胶质瘤细胞C6，24、48 h 和72 h 后，CCK8法检测增殖，并选出合适浓度进行后续试验；不同浓度的 药物作用于细胞24 h 后，吖啶橙法观察细胞形态变化、流式细胞仪检测细胞凋亡、细胞周期和免疫印迹检测蛋白 Bax、Bcl-2 和p-Erk1/2 变化。结果：白藜芦醇与顺铂能协同抑制神经胶质瘤细胞C6 的增殖。联合用药后细胞周 期抑制在S 期。免疫印迹结果显示凋亡蛋白Bax 的表达量增加，而凋亡抑制蛋白Bcl-2 的表达量减少，细胞外调 节蛋白激酶p-Erk1/2 的表达量减少。结论：白藜芦醇与顺铂联合对神经胶质瘤细胞具有相互增敏作用，能够协同 抑制细胞增殖，并通过Ras-Raf-MEK-Erk 信号通路促进其凋亡。     

白藜芦醇通过激活PI3K/AKT通路抑制内皮细胞凋亡的研究

目的观察白藜芦醇对脂多糖作用下人脐静脉血管内皮细胞凋亡的影响,并探讨其作用机制。方法体外培养人脐静脉血管内皮细胞,实验分为5组:空白组给予单纯培养基培养;模型组培养基中加入1000 ng/mL脂多糖孵育24 h;5μmol/L白藜芦醇组和10μmol/L白藜芦醇组培养基中分别先加入5μmol/L、10μmol/L白藜芦醇孵育12 h,再加入1000 ng/mL脂多糖孵育24 h;PI3K抑制剂组培养基中先加入10μmol/L白藜芦醇和10μmol/L PI3K抑制剂LY294002共处理12 h,再加入1000 ng/mL脂多糖孵育24 h。使用CCK-8试剂盒检测各组细胞的增殖能力;流式细胞术检测各组细胞凋亡率;DHE荧光探针检测各组细胞中活性氧(ROS)含量;ELISA检测各组细胞培养液中一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;Western blot法检测各组AKT的磷酸化情况。结果与空白组相比,模型组细胞增殖能力明显降低,细胞凋亡率和细胞中ROS含量及TNF-α、IL-6水平均明显升高,NO水平及P-AKT/AKT表达水平明显降低,差异均有统计学意义(P均<0.05)。与模型组和PI3K抑制剂组相比,10μmol/L白藜芦醇组细胞增殖能力明显升高,细胞凋亡率和细胞中ROS含量及TNF-α、IL-6水平明显下降,NO水平及P-AKT/AKT表达水平明显升高,差异均有统计学意义(P均<0.05)。结论白藜芦醇能够提升脂多糖作用下人脐静脉血管内皮细胞的增殖能力,抑制细胞凋亡,减轻细胞的氧化应激和炎性反应,恢复细胞的分泌功能,可能与其激活PI3K/AKT通路而发挥保护作用有关。     

Resveratrol relieves particulate matter (mean diameter < 2.5 μm)‐induced oxidative injury of lung cells through attenuation of autophagy deregulation

Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM_2.5)‐induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM_2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM_2.5‐induced oxidative injury. The potential role of nuclear factor erythroid‐2‐related factor 2 and autophagy in this progress was explored. Human bronchial epithelial cells were treated with PM_2.5 and the cytotoxicity and oxidative stress markers were determined. The results showed that PM_2.5 decreased cell viability and elevated the level of lactate dehydrogenase. The levels of malondialdehyde and reactive oxygen species were increased by PM_2.5 exposure. PM_2.5 also induced a significant increase of the inflammatory cytokines including interleukin (IL)‐6, IL‐8, IL‐1β and tumor necrosis factor α. Meanwhile, PM_2.5 triggered autophagy formation and alteration of the nuclear factor erythroid‐2‐related factor 2 pathway. Furthermore, human bronchial epithelial cells were co‐treated with PM_2.5 and resveratrol in the presence or absence of 3‐methylamphetamine, an inhibitor of autophagic formation. It was revealed that resveratrol intervention abolished PM_2.5‐induced oxidative injury partially through the suppression of autophagy deregulation. Findings from this study could provide new insights into the molecular mechanisms of pulmonary intervention during PM_2.5 exposure.     

Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices,Metabolic Parameters,and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

Objective: There is a promising perspective regarding the potential effect of resveratrol in preventing and treating metabolic disturbances similar to that of calorie restriction. The aim of this study was to evaluate the effects of calorie-restricted (CR) diet on metabolic parameters and then to investigate whether resveratrol supplementation has beneficial effects similar to CR diet in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: This randomized controlled clinical trial was conducted in 90 patients with NAFLD (males and females) aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m². Participants were assigned to one of three intervention groups as follows: The CR diet group (n = 30) received a prescribed low-calorie diet, the resveratrol group (n = 30) received 600 mg pure trans-resveratrol (2 × 300 mg) daily, and the placebo group (n = 30) received placebo capsules (2 × 300 mg) daily for 12 weeks. Fasting blood samples, anthropometric measurements, and dietary intake and physical activity data were collected for all participants at baseline and at the end of the trial.

Results: CR diet significantly reduced weight (by 4.5%); BMI; waist circumference; waist-to-hip ratio; and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles in participants compared to resveratrol and placebo (all p < 0.05). Significant reductions in weight (by 1.1%) and BMI were found in the resveratrol group compared to the placebo group (p < 0.05). ALT, AST, and lipid profiles did not change significantly in the resveratrol group (all p > 0.05). No significant changes were seen in hepatic steatosis grade, serum glycemic parameters, and high-density lipoprotein cholesterol and sirtuin-1 levels in any group (all p > 0.05).

Conclusions: CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.     

Anti-platelet effects of vitamin supplements in age-related macular degeneration: an in vitro study

Objective: The purpose of this experimental study was to investigate the role of vitamin supplements (Ocuvite, Vitalux Omega, and Nutrof Total) as possible inhibitors of the onset of age-related macular degeneration (AMD).

Materials and methods: The anti-aggregating effect of each vitamin was determined against four accumulative factors namely, platelet activating factor (PAF), adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), and arachidonic acid (AA) in the platelet rich plasma (PRP) of healthy volunteers.

Results: Ocuvite, Vitalux Omega, and Nutrof Total were more potent inhibitors against PAF and ADP compared to TRAP and AA. Among the three vitamins, Nutrof Total displayed more potent inhibitions against TRAP and AA, while against PAF and ADP all the three vitamins revealed similar IC₅₀ values.

Conclusions: The vitamins Ocuvite, Vitalux Omega, and Nutrof Total have anti-aggregating effects and therefore can be used against AMD in healthy volunteers.     

白藜芦醇对急性胰腺炎肺损伤大鼠树突状细胞的影响

目的 观察白藜芦醇（resveratrol,Res）对重症急性胰腺炎（SAP）肺损伤大鼠树突状细胞（DC）的影响.方法 36只SD大鼠随机分为三组：假手术组、SAP模型组、Res治疗组（Res 10 mg/kg）,每组各12只.各组SD大鼠于制模后12 h处死,行胰腺及肺组织病理学检查和评分.提取肺树突状细胞,流式细胞仪检测DC表型CD80表达,并检测IL-12的分泌水平.结果 Res组肺和胰腺组织病理学评分分别为（3.49±1.02）和（6.43±1.40）,而SAP组分别为（6.12±2.02）和（11.00±2.58）,Res组评分均显著降低（P＜ 0.05）.SAP组DC细胞表面分子CD80阳性表达率为（45.3±6.7）％,而Res组为（20.1±3.2）％,显著低于SAP组,差异有统计学意义（P＜0.05）;Res组和SAP组DC分泌IL-12浓度分别为（1 676.5±121.8） g/L和（4 436.4±169.8） g/L,Res组IL-12浓度显著低于SAP组,差异有统计学意义（P＜0.05）.结论 Res能显著减轻SAP时肺和胰腺组织损伤,其机制与抑制肺DC活化有关.     

买麻藤中1个新的含氮芪类化合物

目的 研究买麻藤Gnetum montanum藤茎的化学成分。方法 利用正相硅胶、Sephadex LH-20凝胶、中压制备液相色谱和半制备HPLC等多种柱色谱技术进行分离纯化,并综合运用ESI-MS、HR-ESI-MS、¹H-NMR、¹³C-NMR、DEPT、¹H-¹H COSY、HSQC、HMBC等方法鉴定化合物的结构。结果 从买麻藤藤茎的95%乙醇提取物中分离得到14个化合物,分别鉴定为（Z）-5-（2,4-二羟基-6-（4-羟基-3-甲氧基苯乙烯基）苯基）吡咯烷-2-酮（1）、银松素单甲醚（2）、3-羟基-5,4''-二甲氧基芪（3）、银松素（4）、买麻藤醇（5）、刚果买麻藤素F（6）、异丹叶大黄素（7）、闭苞买麻藤素（8）、白藜芦醇（9）、顺式-ε-葡萄素（10）、ε-葡萄素（11）、双异食用大黄苷元A（12）、顺式-射干素B（13）和小叶买麻藤素A（14）。结论 化合物1为新化合物,命名为顺式买麻藤内酰胺（cis-gnetumamide）,化合物3、10、13和14为首次从该植物中分离得到。     

Primary cilia mediate sonic hedgehog signaling to regulate neuronal‐like differentiation of bone mesenchymal stem cells for resveratrol induction in vitro

Mesenchymal stem cells (MSCs) can differentiate into neuronal‐like cell types under specific conditions. The classical antioxidant inducers such as β‐mercaptoethanol (BME), butylated hydroxyanisol (BHA), and dimethylsulfoxide (DMSO) are limited in clinical because of toxicity. Resveratrol, a safer, natural antioxidant, can stimulate osteoblastic differentiation of MSCs. However, its effect of inducing MSCs to differentiate into neuronal‐like cells is less well studied, and its differentiated mechanisms are not well understood. Sonic hedgehog (Shh) signaling, mediated by the primary cilia, is crucial for embryonic development and tissue differentiation, but relatively little is known about the role of Shh signaling and primary cilia in neuronal‐like differentiation of MSCs. Here we show that primary cilia, harboring patched 1 (Ptc1), are present in growth‐arrested MSCs and that smoothened (Smo) and Gli1 are present in cytoplasm of MSCs, which are important components of the Shh signaling pathway. After resveratrol induction, MSCs acquire neuronal‐like cell morphologies and phenotypes, Smo translocates to the primary cilia, Gli1 enters the nucleus, and expressions of Smo and Gli1 proteins increase, which can be inhibited by cyclopamine, a Smo antagonist. Meanwhile, Smo agonist (SAG) attains similar effects compared with the resveratrol group. These data indicate that resveratrol can induce MSCs to differentiate into neuronal‐like cells and activate Shh signaling pathway in the primary cilia. Moreover, the primary cilia and Shh signaling are essential for resveratrol inducing neuronal‐like differentiation of MSCs. Our finding is important for understanding the neuronal‐like differentiation mechanism of MSCs for resveratrol and promoting its clinical therapeutic utility. © 2014 Wiley Periodicals, Inc.