Abstract
Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines including dopamine (DA). MAO expression is elevated in Parkinson’s disease (PD). An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B)) participates in the generation of reactive oxygen species (ROS), such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen) has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP+)- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP+ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disease whose main symptom is movement impairment due to degeneration of the brain nigrostriatal system
High levels of Monoamine oxidase (MAO)-B positive astrocytes are concentrated in the substantia nigra pars compacta (SNpc), a region of the brain impacted in PD
Caffeic acid which is rich in Juglandis Semen (JS) significantly inhibited the monoamine oxidase B (MAO-B) activity in rat C6 astrocyte cells, and its phenethyl ester derivative protected against 6-hydroxydopamine-induced neuronal degeneration [28,29]
Summary
Parkinson’s disease (PD) is a common neurodegenerative disease whose main symptom is movement impairment (e.g., rigidity, resting tremor, hypokinesia, bradykinesia, and postural instability) due to degeneration of the brain nigrostriatal system This process is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and is accompanied by depletion of striatal dopamine (DA) and its metabolites, including. MPP+ is produced in the astrocytes of the brain and is taken into dopaminergic neurons by dopamine transporters [15,16] It accumulates in the mitochondria and inhibits Complex I of the cell process of respiration [17,18]. Caffeic acid which is rich in JS significantly inhibited the MAO-B activity in rat C6 astrocyte cells, and its phenethyl ester derivative protected against 6-hydroxydopamine-induced neuronal degeneration [28,29]. We have investigated the effects of JS against MPP+-induced ROS and NO generation due to elevation of MAO-B
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