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.     

白藜芦醇与紫檀芪抗氧化活性差异的电化学研究

为揭示白藜芦醇(反式)与其衍生物紫檀芪的抗氧化活性差异的内在原因,对两种物质的氧化机理进行研究。采用循环伏安法考察pH值、富集时间对氧化过程的影响,采用薄层长光程紫外-可见光谱电化学方法原位监测氧化产物的形成。结果表明：紫檀芪在油性碳糊电极表面上的吸附富集作用远强于白藜芦醇;两者的初始氧化都发生在对位羟基上,通过一电子一质子传递步骤生成苯氧自由基中间体;紫檀芪自由基中间体易于耦合迅速转化为二聚体产物,而白藜芦醇自由基在碱性介质中需经历较难进行的中间双键断裂途径,转化为可溶性小分子产物。紫檀芪较强的亲脂性引起的富集作用以及氧化中间体的快速二聚化,是其具有较强抗氧化活性的重要原因。     

不同配方制备紫檀芪纳米乳液及其稳定性

以葵花籽油、橄榄油和中链脂肪酸甘油三酯（MCT）为载体油相,以吐温80（Tween 80）和酪蛋白酸钠（SC）为乳化剂,采用高压均质法制备紫檀芪纳米乳液（pterostilbene nanoemulsions,PTSNE）。研究了油相种类和质量分数、乳化剂类型和质量分数以及添加助乳化剂（甘油）对PTSNE粒径大小的影响。同时考察了环境因素p H（3⁹）、热处理（40¹00℃,60 min）和离子强度（0⁵00 mmol/L Na Cl,0⁵00 mmol/L CaCl₂）对PTSNE稳定性的影响。结果表明:不同载体油相制备的PTSNE粒径大小为:葵花籽油≈橄榄油>MCT,随着油相质量分数升高达到20%时,粒径变大,且储藏稳定性变差。不同乳化剂制备的PTSNE粒径大小为:Tween 809）、热处理（40⁹0℃,60 min）和离子强度（0⁵00 mmol/L Na Cl,0⁵00 mmol/L CaCl₂）环境下均有良好的稳定性;在100℃保温60 min时,其粒径增大了约50 nm。SC制备的PTSNE具有较好的温度稳定性,但在其等电点（p H≈4.6）附近和高离子强度（≥50 mmol/L CaCl₂）环境下出现明显的液滴聚集现象。      

W/O/W型复乳的制备优化及包埋矢车菊素-3-葡萄糖苷效果分析

为了考察大剂量紫檀芪（Pterostilbene,PTE）对纳米乳液特性的影响,本研究构建了富含大剂量PTE的纳米乳液运载体系,同时研究了不同条件（包括pH、盐离子浓度、反复冻融、冻干、离心）PTE对乳液体系的粒径以及流变特性变化的影响。结果表明,大剂量PTE（2%,w/v）使乳液体系的粒径减小、ζ-电位绝对值增加、乳液黏度增加。在2000~8000 r/min的中低离心转速下,大剂量PTE能显著（P<0.05）提高乳液的离心保留率;在不同pH、低盐离子浓度、冻干的处理条件下,大剂量PTE提高乳液体系稳定性。总之,纳米乳液体系对活性物质PTE的负载并不仅产生单向的影响,PTE本身就会影响乳液体系的构建和稳定性,该研究结果为拓展负载功能活性物质的乳液体系的应用提供了理论基础。

     

紫檀芪对急性心肌梗死大鼠心肌功能、心肌纤维化和炎症反应的作用及对Notch1/eIF3a信号通路的影响

目的:分析紫檀芪对急性心肌梗死大鼠心肌功能、心肌纤维化和炎症反应的作用及对Notch1/eIF3a信号通路的影响。方法:选取SPF级Wistar雄性大鼠75只,分为5组,紫檀芪低、中、高剂量组在造模前采用紫檀芪溶液预处理,灌胃剂量为10、20及40 mg/kg的紫檀芪溶液;模型组和正常组灌胃等剂量生理盐水。除正常组外,其他大鼠制备急性心肌梗死(AMI)模型。观察大鼠左心室功能、心脏血流动力指标、心肌组织病理形态和纤维化情况、心肌炎症因子含量、eIF3a与Notch1蛋白、mRNA表达。结果:模型组大鼠左室短轴缩短率(LVFS)、左室射血分数(LVEF)较正常组降低,左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)、收缩末期左室容积(LVESV)和舒展末期左室容积(LVEDV)较正常组升高;紫檀芪低、中、高剂量组大鼠LVFS、LVEF较模型组升高,LVEDd、LVESd、LVESV、LVEDV较模型组降低,差异有统计学意义(P<0.05);模型组大鼠左室压力最大降低速率(－dp/dtmax)、左室压力最大升高速率(＋dp/dtmax)、左心室收缩压(LVSP)较正常组下降,左室舒张末压(LVEDP)较正常组升高;紫檀芪低剂、中、高剂量组大鼠－dp/dtmax、＋dp/dtmax、LVSP较模型组升高,LVEDP较模型组降低,差异有统计学意义(P<0.05);模型组大鼠心肌组织白细胞介素(IL)-6、IL-1β及TNF-α含量较正常组升高;紫檀芪低剂、中、高剂量大鼠心肌组织IL-6、IL-1β及TNF-α含量较模型组降低,差异有统计学意义(P<0.05);模型组大鼠心肌组织eIF3a、Notch1蛋白与mRNA表达较正常组升高;紫檀芪低、中、高剂量大鼠心肌组织eIF3a、Notch1蛋白与mRNA表达较模型组降低,差异有统计学意义(P<0.05)。结论:AMI大鼠心肌炎症和纤维化发展可能和Notch信号通路下游eIF3a表达增加有联系,紫檀芪预处理可明显改善AMI大鼠心室重构,其作用机制可能和抑制eIF3a、Notch1表达有关。     

Modulation of Innate Immune Toxicity by Silver Nanoparticle Exposure and the Preventive Effects of Pterostilbene

Silver nanoparticles pose a potential risk to ecosystems and living organisms due to their widespread use in various fields and subsequent gradual release into the environment. Only a few studies have investigated the effects of silver nanoparticles (AgNPs) toxicity on immunological functions. Furthermore, these toxic effects have not been fully explored. Recent studies have indicated that zebrafish are considered a good alternative model for testing toxicity and for evaluating immunological toxicity. Therefore, the purpose of this study was to investigate the toxicity effects of AgNPs on innate immunity using a zebrafish model and to investigate whether the natural compound pterostilbene (PTE) could provide protection against AgNPs-induced immunotoxicity. Wild type and neutrophil- and macrophage-transgenic zebrafish lines were used in the experiments. The results indicated that the exposure to AgNPs induced toxic effects including death, malformation and the innate immune toxicity of zebrafish. In addition, AgNPs affect the number and function of neutrophils and macrophages. The expression of immune-related cytokines and chemokines was also affected. Notably, the addition of PTE could activate immune cells and promote their accumulation in injured areas in zebrafish, thereby reducing the damage caused by AgNPs. In conclusion, AgNPs may induce innate immune toxicity and PTE could ameliorate this toxicity.     

Pterostilbene Inhibits Vascular Smooth Muscle Cells Migration and Matrix Metalloproteinase‐2 through Modulation of MAPK Pathway

Smooth muscle cells (SMCs) migration and matrix metalloproteinase‐2 (MMP‐2) activation are main roles in atherosclerosis. Pterostilbene (trans‐3, 5‐dimethoxy‐4‐hydroxystilbene) is known to have various pharmacologic effects such as anti‐inflammatory and anticarcinogenic properties. The present study aimed to investigate the anti‐atheroscleroic property of pterostilbene in the rat smooth muscle cell (SMC) A7r9 cell lines and the underlying mechanisms. In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of in A7r9 cell. Pterostilbene was also found to significantly decreased MMP‐2 activity and expression by gelatin zymography and western blot assay in SMC. In the MAPK signaling pathway, western blot assay also indicated that pterostilbene up‐regulated the phosphorylation of extracellular‐signal‐regulated kinase (Erk)1/2. Moreover, inhibition of Erk1/2 by specific inhibitors significantly abolished the pterostilbene‐decreased expression of MMP‐2 and migration/invasion capacities. These findings suggest that pterostilbene inhibited SMC migration and that MMP‐2 activation could be mediated via Erk1/2 phosphorylation. It is further possible that pterostilbene could play a novel role in the treatment of atherosclerosis.