Flavonoids and the Brain: Evidences and Putative Mechanisms for a Protective Capacity

The origin and/or the evolution of brain diseases of high morbidity and mortality such as cerebrovascular diseases, Alzheimer's Dementia or Parkinson's disease have been linked to oxidative stress. Epidemiological or clinical descriptive studies have shown that diets with predominant vegetarian composition or popular beverages like green tea or red wine have beneficial effects on general pathological markers of oxidative stress. The flavonoids, ubiquitous polyphenols in plants and vegetables, have been identified as mainly by responsible for these actions. In apparent agreement with these data, numerous in vitro and in vivo studies have demonstrated a neuroprotective capacity of flavonoids against oxidative or excitotoxic aggressions. Oral flavonoids undergo several metabolic steps and circulate in the blood mainly as metabolites. These metabolites by themselves or after cleavage into non-metabolised flavonoids in the brain would be the active molecules. The intracellular targets of flavonoids are multiple, from chelation of iron to homeostasis of calcium as well as scavenging of free radicals and involvement through kinase modulation, with key intracellular signalling cascades. As key regulators of cell reactivity against oxidative aggressions, the flavonoid molecule can become an ideal template for compounds therapeutically active in stroke, dementia or aging.