Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2′,4′‐pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP‐induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1‐methyl‐4‐phenylpyridine (MPP+)‐mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP+‐induced astroglial activation and nuclear translocation of nuclear factor‐κB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. © 2016 Wiley Periodicals, Inc. Oxidative stress, mitochondrial dysfunction, and inflammation are intimately linked to the pathogenesis of PD. Mitochondrial dysfunction and inhibition of the electron transport chain lead to the generation of ROS, oxidative stress‐induced cell damage, and cell death. Furthermore, the contribution made by oxidative stress could lead to inflammation and exacerbate PD pathologies. Morin effectively modulates mitochondrial dysfunction and ROS production in dopaminergic neurons and also alleviates the activation of astroglia and inflammation.