Ameliorative effect of ethoxylated chalcone-based MAO-B inhibitor on behavioural predictors of haloperidol-induced Parkinsonism in mice: evidence of its antioxidative role against Parkinson's diseases.

Abstract

Parkinson's disease is a progressive neurodegenerative disorder that affects mostly elderly people above the age of 60. Previously, we have reported that the ethoxylated chalcone derivative (E)-1-(4-ethoxyphenyl)-3-(fluorophenyl)prop-2-en-1-one (E7) showed potent, reversible, and competitive MAO-B inhibition with an IC50 value of 0.053 μm. The present study aims to investigate the anti-Parkinson activity of compound E7 in a haloperidol-induced animal model of mice. The disease was induced with haloperidol (1 mg/kg, intraperitoneal route) once daily for 21 days. E7 was given at dose levels of 10, 20, and 30 mg/kg/day for 21 days, consecutively. Behavioural tests were carried out during and at the end of the study. Biochemical analyses such as oxidative stress biomarkers and neurotransmitters were quantified on the brain homogenate at the end of the study. Behavioural results showed that there is a marked improvement in locomotor activity and motor coordination in the treatment group. Oxidative stress biomarkers such as SOD, CAT, and GSH levels were increased dose-dependently with a maximum at 30 mg/kg, whereas the dose-dependent decrease (30 mg/kg) in the MDA and nitrite levels were observed in the treatment groups. Levels of neurotransmitters, such as dopamine, serotonin, and noradrenaline, were increased in the treatment groups while dopamine and noradrenaline levels were more than in the standard treated group. MAO-B level was also decreased dose dependently in the treatment group in comparison with the control group. Based on the findings, it was concluded that the E7 compound exhibited anti-Parkinson activity which was more evident at 30 mg/kg oral dose as evaluated by the haloperidol-induced animal model of mice.