Regulation of Gene Expression through Food—Curcumin as a Sirtuin Activity Modulator

Abstract

The sirtuin family comprises NAD+-dependent protein lysine deacylases, mammalian sirtuins being either nuclear (SIRT1, SIRT2, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5) or cytosolic enzymes (SIRT2 and SIRT5). They are able to catalyze direct metabolic reactions, thus regulating several physiological functions, such as energy metabolism, stress response, inflammation, cell survival, DNA repair, tissue regeneration, neuronal signaling, and even circadian rhythms. Based on these data, recent research was focused on finding molecules that could regulate sirtuins’ expression and/or activity, natural compounds being among the most promising in the field. Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) can induce, through SIRT, modulation of cancer cell senescence, improve endothelial cells protection against atherosclerotic factors, enhance muscle regeneration in atrophy models, and act as a pro-longevity factor counteracting the neurotoxicity of amyloid-beta. Although a plethora of protective effects was reported (antioxidant, anti-inflammatory, anticancer, etc.), its therapeutical use is limited due to its bioavailability issues. However, all the reported effects may be explained via the bioactivation theory, which postulates that curcumin’s observed actions are modulated via its metabolites and/or degradation products. The present article is focused on bringing together the literature data correlating the ability of curcumin and its metabolites to modulate SIRT activity and its consequent beneficial effects.

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model

“…CUR is a natural antioxidant derived from the roots of ginger, a plant in the ginger family 22 . It is considered an activator of SIRT3 28 , 91 , 92 . CUR exerts a protective effect on bone marrow by reducing ROS-stimulated autophagic cell death in a SIRT3-SOD2 pathway-dependent manner 69 .…”

Curcuma aromatica Salisb. Protects from Acetaminophen-Induced Hepatotoxicity by Regulating the Sirt1/HO-1 Signaling Pathway

“…When primary hepatocytes were treated with NAC and then subjected to APAP damage, NAC treatment increased cell viability more effectively than CAS in a concentration-dependent manner ( Supplementary Figure S3 ). The mechanisms of action include the inhibition of oxidative stress-related inflammation via NF-κB signaling [ 33 ] and the amelioration of liver oxidative stress through the induction of antioxidant signaling pathways such as Nrf2 upregulation [ 34 ] and upregulation of antioxidant gene expression (e.g., NQO1, HO-1) through ERK/p38-MAPK pathways [ 35 , 36 ]. The activation of HO-1 may play an important role in the free radical scavenging activity of curcumin [ 37 , 38 ].…”

Influence of Polyphenols on Adipose Tissue: Sirtuins as Pivotal Players in the Browning Process

“…Among these, edible fruits from the genus Citrus mainly contain flavonoids; red grapes are rich in catechins, anthocyanins, stilbenes, and tannins; apples contain procyanidins, epicatechins, and catechins; cereals and legumes contain flavonoids and phenolic acids; cocoa is rich in catechins, procyanidins, anthocyanins, and flavonol glycosides [55]. They share many beneficial effects in a wide range of organs and tissues, exhibiting antioxidant, anti-inflammatory, and anti-senescence properties [56][57][58][59][60][61][62]. Recently, the potential activity of polyphenols in the regulation of lipid metabolism has also aroused particular interest [37,63].…”