Structural basis of the anti-ageing effects of polyphenolics: mitigation of oxidative stress

Abstract

Ageing, and particularly the onset of age-related diseases, is associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Polyphenolic natural products such as stilbenoids, flavonoids and chalcones have been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis and cellular senescence, both in vitro and in vivo. Here we aim to identify the structural basis underlying the pharmacology of polyphenols towards ROS and related biochemical pathways involved in age-related disease. We compile and describe SAR trends across different polyphenol chemotypes including stilbenoids, flavonoids and chalcones, review their different molecular targets and indications, and identify common structural ground between chemotypes and mechanisms of action. In particular, we focus on the structural requirements for the direct scavenging of reactive oxygen/nitrogen species such as radicals as well as coordination of a broader antioxidant response. We further suggest that it is important to consider multiple (rather than single) biological activities when identifying and developing new medicinal chemistry entities with utility in modulating complex biological properties such as cell ageing.

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

“…With respect to their antioxidant activity, flavonoids are believed to prevent diseases that are related to OS via the direct scavenging of reactive oxygen species (ROS) through the donation of a hydrogen atom, activation of antioxidant enzymes, metal (such as iron and copper)-chelating activity, and alleviation of oxidative stress that is caused by nitric oxide (NO) [1,[8][9][10][11]. Antioxidant activity, though, cannot be the sole explanation for the in vivo cellular effects of flavonoids', since antioxidant activity is expressed at flavonoid concentrations that are above 10 M, but their concentration in the circulation does not exceed 2 M [12].…”

“…Several mechanisms of action have been proposed to explain flavonoidsʹ anti-inflammatory activity in vivo, such as antioxidant activity and the modulation of the production of proinflammatory cytokines and gene expression [11]. Interestingly, flavonoids affect the inflammatory process not only by reducing the expression of cytokines and other related inflammatory markers, but also by interacting with proteins that are related to inflammation.…”

Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

“…As well coordinating the antioxidant response, activation of Nrf2 has been demonstrated to increase proteasomal activity, allowing cells to control protein levels by regulated degradation. Activation of Nrf2 increases the expression and activity of the proteasome in a Nrf2-dependant manner [ 90 , 165 ].…”

Role of Resveratrol in Prevention and Control of Cardiovascular Disorders and Cardiovascular Complications Related to Covid-19 Disease: Mode of Action and Approaches Explored to Increase Its Bioavailability

“…Ageing is also a risk factor for developing atherosclerosis and CVD since age-related changes include reduced efficiency of metabolic processes and accumulation of unfavorable molecular species and events [106]. Several strategies have been employed to decelerate ageing and particularly vascular ageing [107,108].…”