The Antithrombotic Agent Pterostilbene Interferes with Integrin αIIbβ3-Mediated Inside-Out and Outside-In Signals in Human Platelets

Platelets play a crucial role in the physiology of primary hemostasis and pathological processes such as arterial thrombosis; thus, developing a therapeutic target that prevents platelet activation can reduce arterial thrombosis. Pterostilbene (PTE) has remarkable pharmacological activities, including anticancer and neuroprotection. Few studies have reported the effects of pterostilbene on platelet activation. Thus, we examined the inhibitory mechanisms of pterostilbene in human platelets and its role in vascular thrombosis prevention in mice. At low concentrations (2–8 μM), pterostilbene strongly inhibited collagen-induced platelet aggregation. Furthermore, pterostilbene markedly diminished Lyn, Fyn, and Syk phosphorylation and hydroxyl radical formation stimulated by collagen. Moreover, PTE directly hindered integrin α_IIbβ₃ activation through interfering with PAC-1 binding stimulated by collagen. In addition, pterostilbene affected integrin α_IIbβ₃-mediated outside-in signaling, such as integrin β₃, Src, and FAK phosphorylation, and reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen as well as thrombin-stimulated fibrin clot retraction. Furthermore, pterostilbene substantially prolonged the occlusion time of thrombotic platelet plug formation in mice. This study demonstrated that pterostilbene exhibits a strong activity against platelet activation through the inhibition of integrin α_IIbβ₃-mediated inside-out and outside-in signaling, suggesting that pterostilbene can serve as a therapeutic agent for thromboembolic disorders.     

Classic NSAID and selective cyclooxygenase (COX)-1 and COX-2 inhibitors in healing of chronic gastric ulcers

Prostaglandins (PG) derived from COX-1 are essential for the maintenance of mucosal integrity but COX-2 isoform synthesizes PG at a site of inflammation. Recently, COX-2 mRNA expression was demonstrated at the ulcer edge during healing of chronic gastric ulcers but the role for expression of COX-2 and its products such as PGE(2) and cytokines including interleukin (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in ulcer healing remains unknown. In this study, Wistar rats with gastric ulcers produced by serosal application of acetic acid (ulcer area 28 mm(2)) received daily treatment either with: (1) vehicle (saline); (2) NS-398 (10 mg/kg-d i.g.) and Vioxx (5 mg/kg-d i.g.), both, highly specific COX-2 inhibitors; (3) meloxicam (5 mg/kg-d i.g.), a preferential inhibitor of COX-2; (4) resveratrol (10 mg/kg-d i.g.), a specific COX-1 inhibitor; (5) indomethacin (5 mg/kg-d i.g); and (6) aspirin (ASA; 50 mg/kg-d i.g.), non-selective inhibitors of both COX-1 and COX-2. At day 3, 7, and 14 after ulcer induction, the animals were sacrificed and the area of gastric ulcers was determined by planimetry and histology, gastric blood flow (GBF) at ulcer base and margin was measured by H(2) clearance technique, and blood was withdrawn for measurement of plasma IL-1beta and TNFalpha levels. The mucosal biopsy samples were taken for the determination of PGE(2) generation by RIA and expression of COX-1, COX-2, IL-1beta, and TNFalpha mRNA by RT-PCR. In vehicle-treated rats, gastric ulcers healed progressively and at day 14 the healing was completed, accompanied by a significant rise in the GBF at ulcer margin. The IL-1beta, TNFalpha, and COX-1 mRNA were detected in intact and ulcerated gastric mucosa, whereas COX-2 mRNA were upregulated only in ulcerated mucosa with peak observed at day 3 after ulcer induction. The plasma IL-1beta level was significantly increased at day 3 and 7 but then declined at day 14 to that measured in vehicle-controls. Indomethacin and ASA, which suppressed PGE(2) generation both in the non-ulcerated and ulcerated gastric mucosa, significantly delayed the rate of ulcer healing and this was accompanied by the fall in GBF at ulcer margin and further elevation of plasma IL-1beta and TNFalpha levels, which was sustained up to the end of the study. Treatment with NS-398 and Vioxx, which caused only a moderate decrease in the PGE(2) generation in the non-ulcerated gastric mucosa, delayed ulcer healing and attenuated significantly the GBF at ulcer margin and PGE(2) generation in the ulcerated tissue, while raising the plasma IL-1beta and TNFalpha similarly to those observed in indomethacin- and ASA-treated rats. Resveratrol, which suppressed the PGE(2) generation in both non-ulcerated and ulcerated gastric mucosa, prolonged ulcer healing and this was accompanied by the fall in the GBF at the ulcer margin and a significant increase in plasma IL-1beta and TNFalpha levels. We conclude that (1) classic NSAID delay ulcer healing due to suppression of endogenous PG, impairment in GBF at ulcer area, and excessive cytokine expression and release, and (2) this deleterious effect of classic NSAID on the healing of pre-existing ulcers can be reproduced by selective COX-1 and COX-2 inhibitors, suggesting that both COX isoforms are important sources of PG that appear to contribute to ulcer healing.     

葡萄穗轴中白藜芦醇、原花色素提取工艺的研究

利用正交实验对葡萄穗轴中白藜芦醇、原花色素的提取条件,即乙醇浓度、固液比、提取时间、提取温度进行了优化.结果表明,60%的乙醇溶液为提取剂,固液比为1:20,在80℃下提取2h为最佳提取条件,通过溶剂萃取进行分离,用紫外分光光度法和香草醛.盐酸法分别测定其含量.在最佳提取条件下,白藜芦醇的提取率为0.083%,原花色素的提取率为0.516%.     

高含量白藜芦醇葡萄酒工艺研究

白藜芦醇是葡萄中的次生代谢物,具有抗氧化、预防心脏病和防癌、防血管松弛和降血脂、抗血小板凝集和抗谤变等作用。因受气候、产地、感染程度、产量、加工工艺等制约．现有葡萄酒中白藜芦醇含量不高、不均衡。在半成品葡萄酒中加入高纯度的白藜芦醇．生产高含量白藜芦醇葡萄酒工艺具有简单实用、易于掌握、白藜芦醇含量易控制、成本低廉、无任何污染和符合绿色环保要求等特点。（孙悟）     

白藜芦醇糖苷类衍生物的设计与合成

以白藜芦醇及其类似物紫檀芪为原料,采用Schmidt成苷法、相转移催化法,分别与溴代糖和乙酰氨基糖反应,得紫檀芪乙酰葡萄糖苷和(E)-5,4'-二叔丁基二甲基硅基-3-(2"-乙酰氨基-3",4",6"-三乙酰葡萄糖二苯乙烯,其结构经红外光谱、核磁共振氢谱和质谱表征.     

多元醇稀释法制备环糊精包裹白藜芦醇的工艺研究

传统的环糊精包裹活性物的制备工艺都是以有机溶剂作为溶解活性物的载体.本研究使用化妆品中常用的多元醇代替有机溶剂,首次采用多元醇稀释法操作工艺.以白藜芦醇为活性物代表,用多元醇溶解,稳定高效地将活性物包埋于羟丙基-β-环糊精中,很好避免了有机溶剂残留的问题,并进行稳定性测试,采用光学电子显微镜观察析出物结构.采用高效液相...     

Poly(L‐lactic acid) with added α‐tocopherol and resveratrol: optical,physical, thermal and mechanical properties

Poly(L ‐lactic acid) (PLLA) films containing various concentrations of two natural antioxidants, α‐tocopherol and resveratrol, were fabricated by a melt compounding and compression molding process. The influence of the antioxidants on the optical properties such as color and UV‐visible light transmission was analyzed. The thermal, mechanical, rheological and physical properties of PLLA films with added antioxidants were assessed. PLLA films with added α‐tocopherol and resveratrol showed a yellowish brown color and the lightness was influenced by the presence of the antioxidants. The glass transition and melting temperatures were significantly reduced with the addition of antioxidants while enhanced thermal stability was observed, which could be a benefit and important for processing and production. PLLA films with added antioxidants were slightly more hydrophobic than neat PLLA. The combination effect of plasticizing and enhancement of the elastic modulus with differing concentrations of two antioxidants played a critical role in the mechanical and thermomechanical properties of PLLA films. The melt viscosity of the PLLA films with added antioxidants was substantially higher than that of neat PLLA. The higher melt viscosity and G′(ω) could be an indication of formation of entanglement between PLLA and the two antioxidants. Copyright © 2012 Society of Chemical Industry     

Enzymatic Writing to Soft Films: Potential to Filter,Store, and Analyze Biologically Relevant Chemical Information

Sensor‐based chemical analyses commonly enlist either the molecular recognition capabilities of biology (e.g., enzyme biosensors) or advanced information processing algorithms (e.g., the electronic nose). Here, a hybrid approach is proposed in which an enzyme is used to “filter” chemical information and write this information to a film which then serves as a permanent storage medium that can be ‘read’ repeatedly, interactively, and by multiple sensor modalities. This approach is demonstrated by analyzing common dietary phenols that are reported to offer health benefits. Specifically, the enzyme tyrosinase is used to convert these phenols into reactive quinones that graft (i.e., write) to a chitosan film. Grafting can be detected by optical, mechanical, and electrochemical sensors. Importantly, grafting confers redox activity to the films and this redox activity can be probed interactively by advanced electrochemical methods that allow the intrinsic redox reactivities to be compared, redox interactions to be identified, and biologically relevant redox activities to be examined. The transfer of chemical and biological information to a film is envisioned to provide broader access to the extensive capabilities offered by sensor technologies and signal processing methodologies.     

Optimising germinated conditions to enhance yield of resveratrol content in peanut sprout using response surface methodology

Peanut sprout has associated with enhance the content of a nonflavonoids known as resveratrol, which influences a variety of functions including against cancer, cardiovascular and delaying ageing. Peanut from Liaoning province of China was used as a material to accumulate resveratrol during germination. The individual effects of soaking temperature and time as well as germination temperature, time and humidity on resveratrol accumulation in 5 days germinated peanut were investigated. Then, based on Box–Behnken design, interactive effects of the germination parameters were evaluated by response surface methodology. The optimum conditions were as follows: soaking temperature at 35 °C, soaking time at 8 h, germination temperature at 29 °C, germination humidity at 90%, and germination time at 5 day. Under the optimum condition, resveratrol content reached 32.87 μg g^?1, which was almost 9.78 times higher than that in the peanut which did not germinate.     

Inductive modulation on P-glycoprotein and cytochrome 3A by resveratrol,a constituent of grapes

Resveratrol has been reported to show various beneficial pharmacological effects. Nowadays, resveratrol dietary supplement (RDS) is available in the market. Cyclosporin (CsA), a probe drug of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4), is an important immunosuppressant. This study investigated the effect of coadministration of RDS on CsA pharmacokinetics.