Mechanisms of Neuroprotection by Flavonoids, Phenolic Acids, Stilbenes, and Lignans

Neurodegenerative and neurological disorders act as a serious global public health problem. These conditions result in oxidative stress, neuronal loss, neuroinflammation, synaptic dysfunction, and mitochondrial impairment. Polyphenolic compounds such as flavonoids, phenolic acids, stilbenes, and lignans have gained attention due to their antioxidant, antinflammatory, cardioprotective, and neuroprotective properties. The underlying mechanism of neuroprotection of these compounds involves inhibiting the activation of cyclin-dependent kinase-5 and GSK3β, activating the PI3K/AKT pathway, increasing antioxidant enzymes, reducing the generation of oxidative species, inhibiting the NF-κB, and activating the NLRP3 pathway. Additionally, they regulate neurotransmitters (dopamine, glutamate), increase neurotrophic factors to support neuronal growth and plasticity, prevent misfolded proteins, and neurotoxicity for neuronal survival. This chapter will discuss the neuroprotective potential of these polyphenols and the current understanding of their neuroprotective mechanism.