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.
