SIRT1 Activation by Natural Phytochemicals: An Overview

Abstract

Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD + as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. In recent years, scientific interest focusing on the identification of SIRT1 modulators has led to the discovery of novel small molecules targeting SIRT1 activity. This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact.

Dietary Anti-Aging Polyphenols and Potential Mechanisms

“…In addition to the direct action on eNOS expression/activity, polyphenols were reported to activate Sirt1 [ 182 , 183 ], which is an upstream regulator of eNOS [ 184 , 185 ], therefore Sirt1-mediated mitochondrial biogenesis might underlie the anti-aging actions of polyphenols against oxidative stress. Indeed, resveratrol treatment increased mitochondrial biogenesis in wild-type mice but not eNOS knockout mice [ 179 ].…”

The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

“…The diversity and complexity of natural products can provide excellent source for bioactive molecules with remarkable efficacy and specificity. Therefore, they hold a great potential for new scaffolds discovery with the ability to modulate therapeutic protein targets [ 41 , 78 , 79 ]. SIRT modulators are compounds that are able to inhibit or activate SIRTs’ activity ( Figure 6 ).…”

“…SIRT modulators are compounds that are able to inhibit or activate SIRTs’ activity ( Figure 6 ). They gained a particular interest as they can regulate (activate or inhibit) their function [ 60 , 61 , 62 , 78 , 79 , 80 , 81 ]. For example, SIRT1 activators have been proposed for treating a range of diseases and disorders such as aging, oxidative stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease and inflammation [ 78 , 79 , 80 , 81 , 82 ].…”

“…To date, several modulators with a wide range of core structures have been identified and characterized [ 41 , 79 ]. Some well-known modulators of SIRTs are shown in Figure 6 and briefly discussed.…”

SIRT1 Antagonizes Oxidative Stress in Diabetic Vascular Complication

“…As discussed above, SIRT1 antagonises oxidative stress via different substrates in DM, implying activating SIRT1 as potent therapeutic strategy. Importantly, SIRT1 can be activated directly or indirectly by some naturally polyphenols in vitro and in vivo , such as resveratrol, quercetin, and catechins ( 122 , 123 ). For instance, resveratrol is one of the well-studied SIRT1 activators that binds to SIRT1 to promote its substrate binding activity.…”