Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1 beta, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.