Programa de Pós-Graduação em Bioquímica, Universidade Federal do Pampa - Campus Uruguaiana, Uruguaiana CEP 97500-970, RS, Brazil.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Campus Uruguaiana, Uruguaiana CEP 97500-970, RS, Brazil.
Neuroscience. 2019 Dec 15;423:122-130. doi: 10.1016/j.neuroscience.2019.09.032. Epub 2019 Nov 4.
Alzheimer's disease (AD) is a neurodegenerative disorder classically characterized by cognitive functions impairment. However, its symptomatology is complex and the depression is one of the most frequent behavioral changes in AD. AD pathology includes neuroinflammation and oxidative stress resulting in the Aβ protein accumulation. Curcumin is a natural phenolic compound that shows antioxidant and anti-inflammatory properties. Nevertheless, therapeutic use of curcumin is limited due to its low bioavailability and biodistribution. In this context, the use of curcumin-loaded nanocapsules (NLC C) emerges to overcome its limitations. Thus, the present study investigated the effects of NLC C on the depressant-like behavior and oxidative stress induced by an animal model of AD. For this, Swiss male mice were divided into five groups. The Aβ, Aβ + NLC C and Aβ + Curcumin groups received Aβ aggregate (3 nmol/3 μL, i.c.v.). Control and NLC C groups received only vehicle. The NLC C were administered via gavage at a dose of 10 mg/kg in alternate days for 12 days. Our results demonstrated that Aβ infusion induced a depressantant-like behavior observed in the tail suspension and forced swimming tests, which was reversed by NLC C treatment. No change was observed in mice locomotion. Furthermore, NLC C reduced the Aβ-generated oxidative stress in the prefrontal cortex, evidenced by the increase in the reactive species levels, superoxide dismutase and catalase activities. Importantly, NLC C were more effective than the free curcumin. Thus, we demonstrated the antidepressant-like and antioxidant effects of NLC C in a mouse model of AD, suggesting its therapeutic potential for this disorder.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征通常为认知功能障碍。然而，其症状复杂，抑郁是 AD 最常见的行为变化之一。AD 病理学包括神经炎症和氧化应激，导致 Aβ 蛋白积累。姜黄素是一种天然酚类化合物，具有抗氧化和抗炎特性。然而，由于其低生物利用度和生物分布，姜黄素的治疗用途受到限制。在这种情况下，使用载姜黄素纳米胶囊（NLC C）来克服其局限性。因此，本研究调查了 NLC C 对 AD 动物模型引起的抑郁样行为和氧化应激的影响。为此，将雄性瑞士小鼠分为五组。Aβ、Aβ+NLC C 和 Aβ+姜黄素组接受 Aβ 聚集体（3 nmol/3 μL，脑室内注射）。对照和 NLC C 组仅接受载体。NLC C 通过灌胃给药，每天交替给药，剂量为 10 mg/kg，共 12 天。我们的结果表明，Aβ 输注诱导了悬尾和强迫游泳试验中观察到的抑郁样行为，NLC C 治疗可逆转这种行为。未观察到小鼠运动发生变化。此外，NLC C 降低了前额叶皮层中由 Aβ 产生的氧化应激，这表现为活性物质水平、超氧化物歧化酶和过氧化氢酶活性的增加。重要的是，NLC C 比游离姜黄素更有效。因此，我们在 AD 小鼠模型中证明了 NLC C 的抗抑郁和抗氧化作用，表明其在该疾病中的治疗潜力。
