Flavonoids-Macromolecules Interactions in Human Diseases with Focus on Alzheimer, Atherosclerosis and Cancer

Flavonoids, a class of polyphenols, consumed daily in our diet, are associated with a reduced risk for oxidative stress (OS)-related chronic diseases, such as cardiovascular disease, neurodegenerative diseases, cancer, and inflammation. The involvement of flavonoids with OS-related chronic diseases have been traditionally attributed to their antioxidant activity. However, evidence from recent studies indicate that flavonoids' beneficial impact may be assigned to their interaction with cellular macromolecules, rather than exerting a direct antioxidant effect. This review provides an overview of the recent evolving research on interactions between the flavonoids and lipoproteins, proteins, chromatin, DNA, and cell-signaling molecules that are involved in the OS-related chronic diseases; it focuses on the mechanisms by which flavonoids attenuate the development of the aforementioned chronic diseases via direct and indirect effects on gene expression and cellular functions. The current review summarizes data from the literature and from our recent research and then compares specific flavonoids' interactions with their targets, focusing on flavonoid structure-activity relationships. In addition, the various methods of evaluating flavonoid-protein and flavonoid-DNA interactions are presented. Our aim is to shed light on flavonoids action in the body, beyond their well-established, direct antioxidant activity, and to provide insights into the mechanisms by which these small molecules, consumed daily, influence cellular functions.