Gutierrez Maria Eduarda Ziani, Savall Anne Suély Pinto, da Luz Abreu Edina, Nakama Kelly Ayumi, Dos Santos Renata Bem, Guedes Marina Costa Monteiro, Ávila Daiana Silva, Luchese Cristiane, Haas Sandra Elisa, Quines Caroline Brandão, Pinton Simone
Postgraduation Program in Biochemistry, Federal University of Pampa (UNIPAMPA), Uruguaiana, RS, Brazil.
Postgraduation Program in Pharmaceutical Science, Federal University of Pampa (UNIPAMPA), Uruguaiana, RS, Brazil.
Neural Regen Res. 2021 Apr;16(4):783-789. doi: 10.4103/1673-5374.295339.
Alzheimer's disease (AD) is a progressive brain disorder and complex mechanisms are involved in the physiopathology of AD. However, there is data suggesting that inflammation plays a role in its development and progression. Indeed, some non-steroidal anti-inflammatory drugs, such as meloxicam, which act by inhibiting cyclooxygenase-2 (COX-2) have been used as neuroprotective agents in different neurodegenerative disease models. The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules (LCN) on cognitive impairment induced by amyloid-beta peptide injection in mice. LCN were prepared by the nanoprecipitation method. Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates (fragment 25-35, 3 nmol/3 μL) or vehicle and were subsequently treated with curcumin-loaded LCN (10 mg/kg) or meloxicam-loaded LCN (5 mg/kg) or meloxicam + curcumin-co-loaded LCN (5 and 10 mg/kg, respectively). Treatments were given on alternate days for 12 days (i.e., six doses, once every 48 hours, by intragastric gavage). Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice. In the inhibitory avoidance test, both meloxicam and curcumin formulations (oil or co-loaded LCN) improved amyloid-beta-induced memory impairment in mice. However, only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test. Moreover, the beneficial effects of meloxicam and curcumin-co-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical COX-2 downregulation. Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical COX-2 modulation. This study was approved by the Committee on Care and Use of Experimental Animal Resources, the Federal University of Pampa, Brazil (approval No. 02-2015) on April 16, 2015.
阿尔茨海默病（AD）是一种进行性脑疾病，其病理生理学涉及复杂机制。然而，有数据表明炎症在其发生和发展中起作用。事实上，一些通过抑制环氧化酶-2（COX-2）发挥作用的非甾体抗炎药，如美洛昔康，已在不同神经退行性疾病模型中用作神经保护剂。本研究的目的是调查脂质核纳米胶囊（LCN）中共纳米包裹的姜黄素和美洛昔康对淀粉样β肽注射诱导的小鼠认知障碍的影响。LCN通过纳米沉淀法制备。雄性瑞士小鼠接受单次脑室内注射淀粉样β肽聚集体（片段25 - 35，3 nmol/3 μL）或溶剂，随后用载姜黄素的LCN（10 mg/kg）或载美洛昔康的LCN（5 mg/kg）或美洛昔康+姜黄素共载LCN（分别为5和10 mg/kg）进行治疗。每隔一天给药12天（即六剂，每48小时一次，通过灌胃）。我们的数据表明，淀粉样β肽注入导致小鼠在抑制性回避和物体识别测试中出现长期记忆缺陷。在抑制性回避测试中，美洛昔康和姜黄素制剂（油剂或共载LCN）均改善了淀粉样β肽诱导的小鼠记忆损伤。然而，在物体识别测试中，只有美洛昔康和姜黄素共载LCN减轻了非厌恶性记忆损伤。此外，美洛昔康和姜黄素共载LCN的有益作用可通过这些药物通过下调皮质COX-2的抗炎特性来解释。我们的研究表明，美洛昔康和姜黄素共纳米包裹的神经保护潜力与皮质COX-2调节有关。本研究于2015年4月16日获得巴西潘帕联邦大学实验动物资源护理与使用委员会批准（批准号02 - 2015）。
