Abstract

Parkinson´s disease (PD) is a major public health problem worldwide that affects millions of people, increasingly prevalent as the population ages. This disease, the most common human neurodegenerative motor disorder, is characterized by a progressive decrease in striatal dopamine content of dopaminergic neurons in the substantia nigra pars compacta. Converging pathogenic factors such as oxidative stress, inflammation, mitochondrial impairment and altered calcium homeostasis, among others, have been described as biochemical mechanisms of neurodegeneration in PD. Presently, quite a few natural flavonoids with potential antioxidants and signaling properties have been investigated and are still in progress to identify hopefully preventive neuroprotective compounds to forestall clinical progression of PD.

Flavonoids are the most abundant plant polyphenolic substances (over 4000 different ones) and they are found in main dietary sources (fruits, vegetables and plant-derived beverages). Chemically, this group of natural products shares a 2-phenylbenzopyran as basic structure (C6-C3-C6), and it is further subdivided into different classes (i.e. flavones, flavanones, flavonols anthocyanins, flavan-3-ols). Related to their structural characteristics, flavonoids can transfer a hydrogen atom to scavenge reactive oxygen species (ROS), chelate metal ions (i.e. iron, copper) and stabilize unpaired electrons by resonance. Structural differences found among individual types of flavonoids as well as glycosylation patterns determine the biological activities of these promising chemoprotective compounds. As neuroprotective agents, flavonoids have been reported to act as direct ROS scavengers, modulate the endogenous enzymatic and nonenzymatic antioxidant defense system and activate and regulate different pro-survival pathways.

This chapter, based on highlighted research articles, focuses on the multiple neuroprotection mechanisms of natural flavonoids in PD, covering the most recent preclinical in vitro and in vivo PD animal models’ studies and clinical trials and providing an overview and challenges that may be helpful for future research.