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

Abstract

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.

• Authors: Maria Eduarda Ziani Gutierrez, Anne Suély Pinto Savall, Edina da Luz Abreu, Kelly Ayumi Nakama, Renata Bem Dos Santos, Marina Costa Monteiro Guedes, Daiana Silva Ávila, Cristiane Luchese, Sandra Elisa Haas, Caroline Brandão Quines, Simone Pinton
• Journal: Neural regeneration research (Neural Regen Res) Vol. 16 Issue 4 Pg. 783-789 (Apr 2021) ISSN: 1673-5374 [Print] India
• PMID: 33063743 (Publication Type: Journal Article)