Neuroprotective Effects of Pomegranate Juice against Parkinson's Disease and Presence of Ellagitannins-Derived Metabolite-Urolithin A-In the Brain.

Małgorzata Kujawska,Piotr Chmielarz,Michael Jourdes,Hanna Szaefer,Violetta Krajka-Kuźniak,Pierre-Louis Teissedre,Michał Szulc,Grzegorz Kreiner,Przemyslaw Łukasz Mikołajczak,Monika Kurpik,Jadwiga Jodynis-Liebert

doi:10.3390/ijms21010202

Abstract

Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate’s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites—urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and α-synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and α-synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.

Highlights

Studies on dietary polyphenols suggest their beneficial role against Parkinson’s disease (PD), which is mainly attributed to antioxidant, anti-inflammatory, and anti-apoptotic activity [1]
We examined whether administration with pomegranate juice to rats intoxicated with rotenone provided any beneficial effects on postural stability and neuronal survival, and we assessed the influence of the treatment on antioxidant, inflammatory, and apoptotic markers as well as α-synuclein level in the midbrain
Panosatluyrsaisl oInf svtaarbiialnitcye (ANOVA) followed by Sidak’s multiple comparisons test. * p < 0.05 vs. control group (Control). # p2

Summary

Introduction

Studies on dietary polyphenols suggest their beneficial role against Parkinson’s disease (PD), which is mainly attributed to antioxidant, anti-inflammatory, and anti-apoptotic activity [1]. Supplementation with pomegranate juice in the drinking water of pregnant and nursing dams has been demonstrated to protect the neonatal brain in an inflammatory [4] and a hypoxic-ischemic (H-I) models [5,6]. These neuroprotective effects have been shown to be attributed to the inhibition of oxidative stress, and a decrease in the production of proinflammatory cytokines [4] and apoptotic proteins [4,5,6]. Since mitochondrial impairment and the associated oxidative stress, neuroinflammation, and apoptosis are proposed to be critical processes for neurodegeneration, the inhibition of production of intracellular reactive oxygen species (ROS) [18,19], nitric oxide [18], and pro-inflammatory cytokines [18,20] and the prevention of activation of proapoptotic caspases 3 and 9 [19] caused by urolithins A and B in neuronal cell lines, support their involvement in the neuroprotection

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