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

作　　者：Maria Eduarda Ziani Gutierrez Anne Suély Pinto Savall Edina da Luz Abreu Kelly Ayumi Nakama Renata Bem Dos Santos Marina Costa Monteiro Guedes Daiana SilvaÁvila Cristiane Luchese Sandra Elisa Haas Caroline Brandão Quines Simone Pinton 

机构地区：[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

出　　处：《Neural Regeneration Research》2021年第4期780-786,共7页中国神经再生研究（英文版）

基　　金：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：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 antiinflammatory 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/3μL)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 curcuminco-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.

关 键 词：Alzheimer’s disease CURCUMIN CYCLOOXYGENASE-2 lipid core nanocapsules MELOXICAM memory rats inflammation 

分 类 号：R453[医药卫生—治疗学] R364[医药卫生—临床医学]