Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson's disease.

Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson's disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells.

Litter reduction-induced obesity promotes early depressive-like behavior and elevated prefrontal cortex GFAP expression in male offspring.

Aims: The present study was developed to investigate how litter reduction-induced obesity promotes early depressive-related behaviors in rodent offspring.

Main Methods: We employed a standardized litter size reduction protocol, dividing litters into groups: normal litters (NL), consisting of six males and six females pups and small litters (SL), comprising two males and two females pups. Maternal behavior was monitored during the initial week of lactation.

Antinociceptive Effect of Dillenia indica (Linn.) Mediated by Opioid and Cannabinoid Systems: Pharmacological and Chemical Studies.

Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D.

Design, synthesis, and biological evaluation of new thalidomide-donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation.

A new series of eight multifunctional thalidomide-donepezil hybrids were synthesized based on the multi-target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti-neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the -benzylpiperidine pharmacophore of donepezil and the isoindoline-1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC value of 3.

Metabolic syndrome accentuates post-traumatic stress disorder-like symptoms and glial activation.

The relationship between individuals with post-traumatic stress disorder (PTSD) and the development of metabolic syndrome (MS) is well understood, but the relationship between individuals with preexisting MS and the development of PTSD is not yet known. Therefore, we evaluated the course of PTSD development in preexisting MS rats and we quantified the glial fibrillary acidic protein (GFAP) and ionized the calcium binding adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental animals. Male Wistar rats were divided into two groups: control or 10 % fructose for 5 weeks.

Maternal protein malnutrition prolongs sickness behavior in male offspring.

Female rats were fed a normal or hypoproteic diet during the phases of gestation and lactation. The male offspring of these rats were grown to adulthood and used to study the effects of maternal protein malnutrition on progeny. The adult male rats were pretreated with either saline or LPS and subjected to behavioral tests 2 and 6 h after administration.

Cafeteria diet during the gestation period programs developmental and behavioral courses in the offspring.

The objective of this study was to investigate the effect of exposure to maternal consumption of a hyperenergetic, highly palatable diet, known as the cafeteria diet, during the gestation period on the development and behavior of offspring. For this, we used pregnant female mice that were fed a normal or a cafeteria diet during the gestation period. The evaluation of maternal behavior in lactating dams was performed from the second to the eighth day postpartum (PND 2-8).

Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates.

A new series of sixteen multifunctional N-benzyl-piperidine-aryl-acylhydrazones hybrid derivatives was synthesized and evaluated for multi-target activities related to Alzheimer's disease (AD). The molecular hybridization approach was based on the combination, in a single molecule, of the pharmacophoric N-benzyl-piperidine subunit of donepezil, the substituted hydroxy-piperidine fragment of the AChE inhibitor LASSBio-767, and an acylhydrazone linker, a privileged structure present in a number of synthetic aryl- and aryl-acylhydrazone derivatives with significant AChE and anti-inflammatory activities. Among them, compounds 4c, 4d, 4g and 4j presented the best AChE inhibitory activities, but only compounds 4c and 4g exhibited concurrent anti-inflammatory activity in vitro and in vivo, against amyloid beta oligomer (AβO) induced neuroinflammation.

Maternal protein malnutrition induces autism-like symptoms in rat offspring.

We tested the correlation between maternal protein malnutrition and autistic-like symptoms using behavioral tests in rodents that measure main behavioral characteristics observed in humans with autism spectrum disorder (ASD). Pregnant female rats were fed a normal diet or a hypoproteic diet during gestation and lactation periods. The litters were weighed every 3 days during lactation, and the offspring were tested in behavioral tasks during infancy (postnatal day (PND) 5: quantification of ultrasonic vocalizations; PND 13: homing behavior test) and adolescence (PND 30-32: open field, hole-board, play social behavior, and object recognition tests) in order to capture the prevalence of some of the core and associated symptoms of ASD.

Experiencing early life maternal separation increases pain sensitivity in adult offspring.

Maternal separation is a widely accepted model for studying long-term behavioral changes produced by events during early life and its association with changes in pain sensitivity. Thus, our objective was to evaluate sensitivity to pain, under different stimuli in adult male and female rats that had undergone early life maternal separation. Animals were subjected to maternal separation from postnatal day (PND) 2-15.

Maternal dipyrone treatment during lactation in mice reduces maternal behavior and increases anxiety-like behavior in offspring.

Dipyrone (metamizole), a powerful drug, is widely used as an analgesic and antipyretic; however, the safety of its use during lactation and the potential impact on the offspring are not well established. This study aimed to determine the effect of maternal dipyrone treatment during lactation on offspring development and emotional behavior and on the dam's maternal behavior. Hence, on postnatal day (PND) 2, drinking water only or drinking water containing dipyrone at doses of 100, 300, and 500mg/kg/day, were offered to lactating mothers up to PND9.

Effect of prenatal ethanol exposure on sexual motivation in adult rats.

Maternal alcohol use during pregnancy adversely affects prenatal and postnatal growth and increases the risk of behavioral deficits. The aim of the present study was to evaluate the effect of prenatal exposure to a moderate dose of alcohol on sexual motivation during adulthood. Rats were prenatally exposed to ethanol by feeding pregnant dams a liquid diet containing 25% ethanol-derived calories on days 6 through 19 of gestation.

Protein malnutrition during pregnancy alters maternal behavior and anxiety-like behavior in offspring.

Objective: The aim of this study was to evaluate the effects of protein malnutrition during pregnancy on maternal behavior, on the early behavior in pups by ultrasonic vocalizations (USVs) emission, and on the behavior of offspring in adulthood in an elevated T-maze.

Methods: Pregnant female rats were fed a normal protein-powdered diet (22% casein; control) or a low-protein (hypoproteic) diet (6% casein; protein restriction) during the first 2 weeks of pregnancy. On the fifth postpartum day (PND5), the number of USV was rated.

Continuous central infusion of cannabinoid receptor agonist WIN 55,212-2 decreases maternal care in lactating rats: consequences for fear conditioning in adulthood males.

In lactating rats, maternal behavior consists of several integrated elements designed to promote care and nutrition of the offspring to ensure their survival. Given previous studies showing the role of the brain endocannabinoid system in maternal behavior, the objective of this work was to determine which changes in maternal care occur during continuous intracerebroventricular infusion of a cannabinoid receptor agonist (WIN 55,212-2). Maternal behavior was scored daily in 4 sessions of 72 min each (3 during the light phase and 1 during the dark phase).

The CB1 cannabinoid receptor mediates glucocorticoid-induced effects on behavioural and neuronal responses during lactation.

It has been shown that glucocorticoids can modulate oxytocin (OT) secretion and disrupt maternal behaviour. Because the CB1 receptor (CB1R) has been implicated in some rapid glucocorticoid-induced actions, the present study aimed to evaluate the possible involvement of CB1Rs in maternal behaviour and neuronal activation during lactation. For this purpose, lactating female rats were pre-treated with dexamethasone (DEX) or saline, followed by treatment with AM251, a CB1R antagonist, or vehicle 90 min later.

Antidepressant-like activity of Sonchus oleraceus in mouse models of immobility tests.

The aim of the present work is to evaluate the putative antidepressant-like effects of hydroethanolic and dichloromethanic extracts from the aerial parts of Sonchus oleraceus (Family Asteraceae) on the performance of male mice in the forced swimming test (FST) and tail suspension test (TST) models predictive of depression. The hydroethanolic and dichloromethanic extracts, both in doses of 30, 100, and 300 mg/kg, were orally administered 1 hour before carrying out the FST or the TST. The immobility time in both the FST and the TST was significantly reduced by acute oral treatment with the extracts (dose range, 100-300 mg/kg), without accompanying changes in ambulation, as assessed in an open-field test.

Antinociceptive effect of the extract of Morus nigra leaves in mice.

Morus nigra has been used to relieve pain in Brazilian folk medicine. This study was conducted to establish the antinociceptive properties of dichloromethane extract from leaves of M. nigra.

Anxiolytic-like effect of Sonchus oleraceus L. in mice.

Ethnopharmacological Relevance: Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system.

Evaluation of the antinociceptive activity of extracts of Sonchus oleraceus L. in mice.

Ethnopharmacological Relevance: Sonchus oleraceus L. has been used to relieve pain in Brazilian folk medicine.

Aim Of The Study: Sonchus oleraceus L.