Modulation of nitric oxide signaling by flavonoids: implications for neurodegeneration

The worldwide burden of neurodegenerative diseases (NDDs) has increased significantly during the last decades. Nitric oxide (*NO), a neurotransmitter, plays critical functions in the activation of numerous inflammatory processes. Although physiological *NO is required for protection against a wide range of infections, oxidative stress, and inflammatory cascades, excessive or dysregulated *NO production can contribute to cellular damage, exacerbating oxidative stress and inflammation, and potentially leading to various pathological conditions, including NDDs. Thus, reducing the overproduction of *NO is a promising treatment strategy for NDDs. Several substances have been investigated for the treatment of NDDs; however, they offer minimal clinical advantages and numerous side effects. Lifestyle modifications, particularly nutrition, can play a significant role in the battle against and prevention of various diseases. Natural flavonoids, a diverse class of chemicals containing phenolic groups found in numerous plants, have potential anti-oxidant, anti-inflammatory, and anti-apoptotic characteristics. The current review discusses the mechanism of *NO generation and its implication in NDDs via the modulation of molecular pathways by flavonoids to inhibit the *NO pathway.