A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.

Protective effects of chrysin against the neurotoxicity induced by aluminium: In vitro and in vivo studies.

Chronic exposure to aluminium (Al) can contribute to the progression of several neurological and neurodegenerative diseases. Al is a metal that promotes oxidative damage leading to neuronal death in different brain regions with behavior, cognition, and memory deficits. Chrysin is a flavonoid found mainly in honey, passion fruit, and propolis with antioxidant, anti-inflammatory, and cytoprotective properties. In this study, we used an integrated approach of in vitro and in vivo studies to evaluate the antioxidant and neuroprotective effects of chrysin against the neurotoxicity elicited by aluminium chloride (AlCl3). In in vitro studies, chrysin (5 µM) showed the ability to counteract the early oxidative stress elicited by tert-butyl hydroperoxide, an oxidant that mimics the lipid peroxidation and Fenton reaction in presence of AlCl3 as well as the late necrotic death triggered by AlCl3 in neuronal SH-SY5Y cells. In vivo studies in a mouse model of neurotoxicity induced by chronic exposure to AlCl3 (100 mg/kg/day) for ninety days then corroborated the antioxidant and neuroprotective effect of chrysin (10, 30, and 100 mg/kg/day) using the oral route. In particular, chrysin reduced the cognitive impairment induced by AlCl3 as well as normalized the acetylcholinesterase and butyrylcholinesterase activities in the hippocampus. In parallel, chrysin counteracted the oxidative damage, in terms of lipid peroxidation, protein carbonylation, catalase, and superoxide dismutase impairment, in the brain cortex and hippocampus. Lastly, necrotic cells frequency in the same brain regions was also decreased by chrysin. These results highlight the ability of chrysin to prevent the neurotoxic effects associated with chronic exposure to Al and suggest its potential use as a food supplement for brain health.