Protective effects of flavonoids against Alzheimer’s disease-related neural dysfunctions

Abstract Senile ages of human life is mostly associated with developmental of several neurological complicated conditions including decreased cognition and reasoning, increased memory loss and impaired language performance. Alzheimer‘s disease (AD) is the most prevalent neural disorder associated with dementia, consisting of about 70% of dementia reported cases. Failure of currently approved chemical anti-AD therapeutic agents has once again brought up the idea of administering naturally occurring compounds as effective alternative and/or complementary regimens in AD treatment. Polyphenol structured neuroprotecting agents are group of biologically active compounds abundantly found in plants with significant protecting effects against neural injuries and degeneration. As a subclass of this family, Flavonoids are potent anti-oxidant, anti-inflammatory and signalling pathways modulatory agents. Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) pathways are both affected by Flavonoids. Regulation of pro-survival transcription factors and induction of specific genes expression in hippocampus are other important anti AD therapeutic activities of Flavonoids. These agents are also capable of inhibiting specific enzymes involved in phosphorylation of tau proteins including β-secretases, cyclin dependent kinase 5 and glycogen synthase. Other significant anti AD effects of Flavonoids include neural rehabilitation and lost cognitive performance recovery. In this review, first we briefly describe the pathophysiology and important pathways involved in pathology of AD and then describe the most important mechanisms through which Flavonoids demonstrate their significant neuroprotective effects in AD therapy.