Flavonoids as Sirtuin Modulators

Abstract

Sirtuins (SIRTs) are described as NAD+-dependent deacetylases, also known as class III histone deacetylases. So far, seven sirtuin genes (SIRTS 1–7) have been identified and characterized in mammals and also known to occur in bacteria and eukaryotes. SIRTs are involved in various biological processes including endocrine system, apoptosis, aging and longevity, diabetes, rheumatoid arthritis, obesity, inflammation, etc. Among them, the best characterized one is SIRT1. Actually, small molecules seem to be the most effective SIRT modulators. Flavonoids have been reported to possess many positive effects favrable for human health, while a relatively less research has been reported so far on their funcions as SIRT modulation mechanisms. In this regard, we herein aimed to focus on modulatory effects of flavonoids on SIRTs as the most common secondary metabolites in natural products. Our literature survey covering the years of 2006-2021 pointed out that flavonoids frequently interact with SIRT1 and SIRT3 followed by SIRT6. It can be also concluded that some popular flavonoid derivatives, e.g. resveratrol, quercetin, and catechin derivatives came forward in terms of SIRT modulation.

The Anticancer Effect of a Flavonoid-Rich Extract of Bergamot Juice in THP-1 Cells Engages the SIRT2/AKT/p53 Pathway

“…In the last decade, SIRTs have been extensively studied as potential molecular targets in several age-related diseases. Of note, small molecules including some flavonoids appeared to be effective SIRT modulators [ 46 ]. Previously, we have investigated the role of BJe and of its flavonoids against SIRT1, one of the seven isoforms of the sirtuin family, in an in vitro model of inflammation, observing a modulation of this sirtuin [ 47 ].…”

Amentoflavone Mitigates Cyclophosphamide-Induced Pulmonary Toxicity: Involvement of -SIRT-1/Nrf2/Keap1 Axis, JAK-2/STAT-3 Signaling, and Apoptosis

“…These favorable effects may be attributed to the ability of AMV to increase the genetic expression of SIRT1 with a subsequent increase in Nrf2 content in the pulmonary tissues, which restores the prooxidant/antioxidant balance to normal values [16,42]. In addition, the enhancement of the histone deacetylase activity of SIRT1 mediated by AMV may underlie the mitigating effects of AMV detected in the present study on the inflammatory cascade [16,43].…”

Cell Survival, Death, and Proliferation in Senescent and Cancer Cells: the Role of (Poly)phenols

“…Numerous studies have focused on quercetin anticancer activities, and various antitumoral molecular mechanisms have been highlighted in cancer cells, from induction of apoptosis and reduced proliferation to cell cycle arrest and inhibition of metastasis [ [215] , [216] , [217] ]. Multiple targets have been demonstrated in cancer cells, including modulation of NF-κB, sirtuins, cyclins, and other proteins involved in cell cycle regulation, heat shock protein 70, antiapoptotic proteins coded by Bcl-xL and Bcl-2, and cytochrome c oxidase subunit 2, p-JNK/c-Jun axis, PI3K/Akt/mTOR pathway, as well as upregulation of proapoptotic factors like p53, p21, Bid, Bax, Bad, cytochrome c, caspase-3, and caspase-9 [ [217] , [218] , [219] , [220] , [221] , [222] ].…”