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

Abstract

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.

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

“…At present, it is believed that due to the complex pathophysiology of neurodegenerative diseases, potential therapeutic agents must display multi-target activities [180]. In this regard, bioactive compounds of natural origin, particularly those with a polyphenolic backbone, are highly appreciated as potential therapeutics due to their relative safety and multifunctional biological and pharmacological activities that target many cellular events related to neurodegeneration [56,66,123,[181][182][183].…”

Umuhengerin Neuroprotective Effects in Streptozotocin-Induced Alzheimer’s Disease Mouse Model via Targeting Nrf2 and NF-Kβ Signaling Cascades

“…In recent years, regular intake of food rich in flavonoids has been linked with humans’ augmented cognitive abilities via the protection of neurons against oxidative stress, and the inhibition of AChE and β-secretase activities [ 9 ]. Moreover, these are shown to be capable of augmenting vascular blood flow and initiating neurogenesis [ 10 ].…”

Mangiferin and Hesperidin Transdermal Distribution and Permeability through the Skin from Solutions and Honeybush Extracts (Cyclopia sp.)—A Comparison Ex Vivo Study

“…The intensity of fluorescence in the epidermis and dermis after hesperidin application proved the presence of free hesperidin, which did not interact with skin macromolecules [68]. The permanent hesperidin interaction with molecules of the dermis extracellular matrix (ECM) was generally slight, though the mechanism of the protection can differ from the conventional antioxidant trail [75][76][77]. Nevertheless, the experiment was carried out ex vivo, and it should be emphasised that in a living organism, the partition of free hesperidin and that associated with macromolecules could be different.…”