Protective Effect of Chinonin in MPTP-Induced C57BL/6 Mouse Model of Parkinson’s Disease

Abstract

The aims of this study were to investigate the effect of chinonin in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice and to examine the possible mechanisms. The neurotoxin MPTP was employed to create a subacute Parkinson's disease (PD)-like model in C57BL/6 mice. Chinonin (10, 20, 40 mg/kg body weight) was intraperitoneally administered 0.5 h after MPTP (30 mg/kg) injection for 7 d consecutively. Chinonin showed neuroprotective effects in the MPTP-treated mice PD model by ameliorating motor impairment in the catwalk and open-field tests. Consistently, chinonin reduced loss of dopaminergic neurons in the substantia nigra and prevented depletion of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid and homovanillic acid in the striatum of mice. Compared with the MPTP group, in the chinonin plus MPTP groups significant increases of superoxide dismutase activity and glutathione levels were observed as well as a distinct reduction of lipid peroxidation product malondialdehyde in the striatum. Taken together, we propose that chinonin exerts neuroprotective effects in C57BL/6 mouse model of PD and these effects may be due to chinonin's antioxidative property. Key words chinonin; Parkinson's disease (PD); neuroprotection; behavior; oxidative stressParkinson's disease (PD) is a major neurodegenerative disorder characterized pathologically by a progressive loss of dopaminergic neurons and clinically by resting tremors, rigidity, slowness of movement and postural instability.1) Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), produces neuropathological and clinical hallmarks in humans, monkeys and mice that closely resemble idiopathic parkinsonism.2,3) MPTP is transformed to the 1-methyl-4-phenylpyridinium ion (MPP + ) by monoamine oxidase type B after administration. 4) Then MPP + is selectively absorbed by the dopaminergic neurons in the substantial nigra via the dopamine transporter and impairs mitochondrial respiration by inhibiting complex I, thereby blocking the production of ATP and lead to the production of reactive oxygen species (ROS). 5) Therefore, MPTP acted as a pro-oxidant in the progress of PD in MPTP-induced mouse.Although the etiologic mechanisms of PD are still obscure, oxidative injury is considered as a pivotal role in disease pathogenesis.6,7) Chinonin (Fig. 1), a natural multi-phenols compound also named Mangifera indica, has been reported to possess anti-oxidative, anti-inflammatory, anti-diabetic, anti-platelet aggregator, antiviral, and anti-depressant properties.8) Given its anti-oxidative property, chinonin have been extensively used in the Indian sub-continent as food additives and in cosmetics and medicines. 9) Besides, chinonin is able to cross the blood brain barrier and has the real potential to ameliorate the oxidative stress observed in neurodegenerative disorders.10,11) Its antioxidant properties have been extensively evaluated in various cell lines, including neurons.12) For example, A...

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