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

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.

Curcumin-Loaded Nanocapsules Reverses the Depressant-Like Behavior and Oxidative Stress Induced by ß-Amyloid in Mice.

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 Aß 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 Aß, Aß + NLC C and Aß + Curcumin groups received Aß25-35 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 Aß 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 Aß-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.

(3Z)-5-Chloro-3-(Hydroxyimino)indolin-2-one attenuates hyperglycemia, increased hepatic glycogen content and hepatic damage induced by malathion acute exposure in rats.

BACKGROUND: Organophosphorus pesticides (OP's) are heavily constituted in agriculture, gardens, home and veterinary and although it is useful, there are concerns about the environment, safety and health of human and animals. In this study, we investigated the effects of a new oxime, (3Z)-5-Chloro-3-(Hydroxyimino)indolin-2-one (OXIME) against the alterations induced by malathion, an OP insecticide, acute exposure on markers of hepatic damage, glucose homeostasis, oxidative stress in rats cholinesterase (ChE) activity in rats. METHODS: Adult male Wistar rats were divided into four groups: Control; Malathion; OXIME; and Malathion+OXIME. Twelve hours after co-treatment with malathion (250 mg/kg, i.p.) and/or OXIME (50 mg/kg, i.g.), the plasma and liver samples were collected for biochemical analyses. RESULTS: The OXIME blocked the increase of plasma markers of hepatic function (AST and ALP) and the enzymatic inhibition of catalase and glutathione reductase in the liver of malathion-treated rats. Moreover, the hepatic cholinesterases inhibition induced by malathion acute exposure was suppressed by OXIME treatment. As assessed, a single dose of OXIME lowered the glycemia levels and hepatic glycogen content enhanced by malathion. CONCLUSIONS: This study suggests promise effects of (3Z)-5-Chloro-3-(Hydroxyimino) indolin-2-one against the hyperglycemia and the hepatic damage induced by malathion acute exposure, as well as its use as a ChE activity reactivator.