The oxidative stress leading to degenerative changes in the brain of Alzheimer’s disease (AD) is evident. Our aim was to evaluate the therapeutic and protective effects of pomegranate extract (PE) and pomegranate extract-loaded nanoparticles (PE nano) in an AlCl 3-induced AD rat model. Nanoparticles were synthesized with a PE load of 0.68% w/w, and 70 male Wistar rats were divided into 7 groups: Group I was the control, Group II received PE., Group III received PE nano for 2 weeks, Group IV received AlCl 3 (50 mg/kg) daily orally for 4 weeks, Group V received PE for 2 weeks, Group VI received PE nano for 2 weeks, and Groups V and VI were started after AlCl 3 administration was stopped. Group VII received PE for 2 weeks and was stopped before AlCl 3 was administered. The Results revealed that the discrimination index in the novel object recognition test was the least in AD rat model but increased in cases protected with PE treated with PE nano. Similar results were shown based on calculating the brain weight/body weight percent. The biomarkers of antioxidant activity (catalase, glutathione and total antioxidant activity) in brain homogenate were significantly increased in groups treated with either PE or PE nano. The thiobarbituric acid reactive substance measured to estimate lipid peroxidation was significantly increased in AD rat model and decreased in groups protected with PE or treated with PE nano. Histopathological studies using hematoxylin and eosin, cresyl violet, and silver stains revealed hyaline degeneration, chromatolysis, and hallmarks of AD; neurofibrillary tangles and the senile plaques in brains of AD rat model. Restoration of the histological architecture, Nissl granules, and minimal appearance of hallmarks of AD characterized brains treated with PE or PE nano. In conclusion, PE was more effective as a protectant than a therapeutic measure in alleviating the antioxidant, lipid peroxidative effects and histopathological hallmarks in AD brains. But, the therapeutic PE-loaded nanoparticles increased the efficacy of active components and produced similar results as the protective PE.

氧化应激导致阿尔茨海默病（AD）大脑发生退行性变化是显而易见的。我们的目的是评估石榴提取物 (PE) 和负载石榴提取物的纳米颗粒 (PE nano) 在 AlCl 3 诱导的 AD 大鼠模型中的治疗和保护作用。合成纳米颗粒时，PE 负载量为 0.68% w/w，70 只雄性 Wistar 大鼠分为 7 组：I 组为对照组，II 组接受 PE，III 组接受 PE 纳米 2 周，IV 组接受 AlCl每天口服3(50mg/kg)，持续4周，V组接受PE，持续2周，VI组接受PE nano，持续2周，V和VI组在停止AlCl 3 给药后开始。 VII组接受PE 2周并在施用AlCl 3 之前停止。结果显示，在AD大鼠模型中，新物体识别测试中的辨别指数最低，但在经过PE纳米处理的PE保护的情况下，辨别指数有所增加。基于计算脑重量/体重百分比显示了类似的结果。在用 PE 或 PE 纳米处理的组中，脑匀浆中的抗氧化活性生物标志物（过氧化氢酶、谷胱甘肽和总抗氧化活性）显着增加。为评估脂质过氧化而测量的硫代巴比妥酸反应物质在 AD 大鼠模型中显着增加，而在用 PE 保护或用 PE 纳米处理的组中减少。使用苏木精和曙红、甲酚紫和银染色进行的组织病理学研究揭示了透明变性、色谱溶解和 AD 的特征； AD大鼠模型大脑中的神经原纤维缠结和老年斑。 组织学结构、尼氏颗粒的恢复以及用 PE 或 PE 纳米处理的 AD 特征大脑的最小外观特征。总之，在减轻 AD 大脑中的抗氧化、脂质过氧化作用和组织病理学特征方面，PE 作为保护剂比治疗措施更有效。但是，治疗性 PE 负载纳米颗粒提高了活性成分的功效，并产生了与保护性 PE 相似的结果。