中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 780-786.doi: 10.4103/1673-5374.295339

• 原著:退行性病与再生 • 上一篇    下一篇

美洛昔康与姜黄素共负载纳米胶囊可改善淀粉样β蛋白诱导的认知功能障碍

  

  • 出版日期:2021-04-15 发布日期:2020-12-22
  • 基金资助:

    南里奥格兰德州科学基金会(FAPERGS);国家技术和科学发展顾问(CNPq)基金和学生奖学金

Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice#br#

Maria Eduarda Ziani Gutierrez1, Anne Suély Pinto Savall1, Edina da Luz Abreu1, Kelly Ayumi Nakama2, Renata Bem Dos Santos2, Marina Costa Monteiro Guedes1, Daiana Silva Ávila1, Cristiane Luchese3, Sandra Elisa Haas1, 2, Caroline Brandão Quines1, *, Simone Pinton1, *#br#   

  1. 1 Postgraduation Program in Biochemistry, Federal University of Pampa (UNIPAMPA), Uruguaiana, RS, Brazil;  2 Postgraduation Program in Pharmaceutical Science, Federal University of Pampa (UNIPAMPA), Uruguaiana, RS, Brazil;  3 Postgraduation Program in Biochemistry and Bioprospecting, Federal University of Pelotas (UFPEL), Capão do Leão, RS, Brazil 
  • Online:2021-04-15 Published:2020-12-22
  • Contact: Caroline Brandão Quines, PhD, carol_quines@hotmail.com; Simone Pinton, PhD, sipinton@gmail.com.
  • Supported by:
    This study was supported by the Rio Grande do Sul Science Foundation (FAPERGS), grants # 16/2551-0000207-0 and 16/0526-5 (PRONUPEQ)  (to SP), National Counsel of Technological and Scientific Development (CNPq) (Universal grants # 423435/2016-7 and 460122/2014-2) and for student scholarships (to CL, SEH and DSÁ). 

摘要:

有研究表明,炎症在阿尔茨海默病的发展进程中有重要作用,而通过抑制环氧合酶2(COX-2)起作用的非甾体抗炎药(NSAIDs)美洛昔康对神经退行性疾病有神经保护作用。为研究美洛昔康与姜黄素共负载纳米胶囊对淀粉样β蛋白诱导小鼠认知功能障碍的影响。实验首先给予雄性小鼠单次脑室内注射淀粉样β蛋白25-35(3 nmol /3μL)建立阿尔茨海默病动物模型,随后灌胃单独负载姜黄素或美洛昔康的纳米胶囊或两者共负载的纳米胶囊,连续12d。抑制性回避测试结果显示,美洛昔康与姜黄素共负载纳米胶囊改善了淀粉样β蛋白25-35诱导的小鼠记忆功能障碍。免疫印迹检测结果显示,美洛昔康与姜黄素共负载纳米胶囊可抑制前额叶皮质环氧合酶2的表达。这些结果表明,美洛昔康与姜黄素共负载纳米胶囊对阿尔茨海默病有神经保护作用,该作用与调节大脑皮质环氧合酶2表达有关。

https://orcid.org/0000-0002-3818-1690 (Caroline Brandão Quines); 

https://orcid.org/0000-0001-6630-7329 (Simone Pinton)

Abstract: Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease. 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 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 cyclooxygenase-2 downregulation. Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-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. 

Key words: Alzheimer’s disease, curcumin, cyclooxygenase-2, lipid core nanocapsules, meloxicam, memory, rats, inflammation