Polyphenols in Parkinson’s Disease: A Systematic Review of In Vivo Studies

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier. The beneficial effects of polyphenols are demonstrated by the results of behavioral examinations, mainly related to motor and cognitive capabilities, histopathological and immunohistochemical examination concerning the protection of dopaminergic neurons, analyses of dopamine and the concentration of its metabolites, as well as mechanistic studies regarding the modulation of oxidative stress, neuroinflammation, cellular iron management, proteinopathy, and additionally the regulation of signaling pathways. Importantly, data about brain distribution of the metabolic derivatives of the reviewed polyphenols are crucial for the justification of their nutritional intake in neuroprotective intervention, as well as for the identification of potential targets for a novel therapeutic approach to Parkinson’s disease.

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

“…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]. The current research trends also cover their metabolic derivatives, in particular, bioavailable gut microbiota metabolites, which offer a novel preventive approach for the disease [2].…”

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

“…Interestingly, multiple mouse models support the notion that gut metabolites are associated with brain development and function (48,90,91). Some metabolites are closely linked with neurological disorders, either to positive or negative outcomes (92,93). Several examples have been reported of gut metabolites entering circulation and directly affecting the brain, as well as cases where metabolites stimulate pathways in the gut, immune, or autonomic nervous system and exert changes to the brain and to behavior (94)(95)(96)(97).…”

Lipids Nutrients in Parkinson and Alzheimer’s Diseases: Cell Death and Cytoprotection

“…In the future, micro-and nanoencapsulation of oils and fatty acids associated with targeted therapies could help to optimize the efficiency of these compounds, whose activities depend both on the degree of degradation in the gastrointestinal tract and on the passage through the blood-brain barrier. Lipid nutrients are certainly a valuable source for developing therapies, but there are also other molecules such as polyphenols, whose properties have already been demonstrated in neurodegenerative diseases and which could be used in combination with these lipids [139,140]. Figure 2.…”