Effects of eugenol on the behavioral and pathological progression in the MPTP-induced Parkinson's disease mouse model

Abstract

Parkinson's disease (PD) is the world's second most common neurological disorder. Oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. Eugenol is a phytochemical with potent antioxidant and anti-inflammatory activity. The present investigation is aimed to study the effect of eugenol in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of PD and its relationship to antioxidant effect. The effects of seven days of oral pre-treatment and post-treatment with three doses of eugenol (25, 50 and 100 mg/kg/day) were investigated against the MPTP-induced PD mouse model. In addition to the assessment of behavioural parameters using various tests (actophotometer, beam walking test, catalepsy, rearing, rotarod), biochemical parameters including lipid peroxidation and reduced glutathione levels in brain tissues, were also estimated in this study. The binding mode of eugenol in the human myeloid differentiation factor-2 (hMD-2) was also studied. Results showed that MPTP administration in mice resulted in the development of motor dysfunction (impaired motor coordination and hypo locomotion) similar to that of PD in different behavioural studies. Pre-treatment with eugenol reversed motor dysfunction caused by MPTP administration while post-treatment with eugenol at a high dose aggravated the symptoms of akinesia associated with MPTP administration. MPTP resulted in increased lipid peroxidation while decreased reduced glutathione levels in the brains of mice. MPTP-induced increased lipid peroxidation and attenuated levels of reduced glutathione were found to be alleviated with eugenol pre-treatment while augmented with eugenol post-treatment. Eugenol showed a binding affinity of -6.897 kcal/mol against the MD2 coreceptor of toll-like receptor-4 (TLR4). Biochemical, as well as neurobehavioral studies, showed that eugenol is having a protective effect, but does not have a curative effect on PD.