From:  The role of the resveratrol-sirtuin axis in the treatment of metabolic dysfunction-associated diseases

 Mechanisms of RSV-targeted SIRT1 in the treatment of CVDs.

RSV-targeted
SIRTS
Mechanisms of actionRegulation of substrates and pathwaysRoles in diseasesResearch objectsReferences
SIRT1↑SIRT1
↓FOXO1 acetylation
↓Bim
RSV enhances SIRT1 deacetylase activity, leading to decreased acetylation of FOXO1 and subsequent downregulation of the pro-apoptotic protein Bim.Inhibits the apoptosis of myocardial cells and protects against cardiac aging and age-related cardiac dysfunction.Male senescence-accelerated mice prone mice[102]
SIRT1↑SIRT1
↓p53 acetylation
↓Ferroptosis-related genes
↓Lipid peroxidation
RSV activates SIRT1 deacetylase activity, thereby inhibiting cardiomyocyte ferroptosis and reducing lipid peroxidation stress.Attenuates cardiomyocyte ferroptosis and decelerates heart failure progression.C57BL/6 mice;
Human-induced pluripotent stem cell-derived cardiomyocytes
[103]
SIRT1↑SIRT1
↓TGF-β1
↓p-Smad3
RSV restores SIRT1 function suppressed by pressure overload, thereby suppressing TGF-β1/Smad3-mediated programs of cardiac hypertrophy and fibrosis.Attenuates pressure overload-induced cardiac hypertrophy and fibrosis.Rat;
NCMs
[104]
SIRT1↑SIRT1
↓PGC-1α/NRF-1/NRF-2 /TFAM
↑Mitochondrial
↑ATP/↓ROS
RSV activates SIRT1 to deacetylate PGC-1α and improve mitochondrial function in diabetic cardiomyopathy.Alleviates cardiac dysfunction in diabetic cardiomyopathy by preserving mitochondrial function and energy metabolism.SIRT1flox5-6/flox5-6;
Myh6-Cre+ transgenic mice;
H9c2 cardiomyoblast cell;
H9c2 embryonic rat heart-derived cell
[105]
SIRT1↑SIRT1
↑NRF2
↑Antioxidant gene
↓ROS
RSV synergizes with FGF1 to activate SIRT1-NRF2 signaling and enhance antioxidant defense.Attenuates doxorubicin-induced cardiotoxicity by reducing oxidative stress and improving cardiac function.C57BL/6J male mice;
H9c2 cardiomyoblast cell
[106]

Bim: Bcl-2-interacting mediator of cell death; CVDs: cardiovascular diseases; FGF1: fibroblast growth factor 1; FOXO1: forkhead box O1; NCMs: neonatal rat cardiomyocytes; NRF2: nuclear factor erythroid 2-related factor 2; p53: tumor protein p53; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; p-Smad3: phosphorylated Sma- and mad-related protein 3; ROS: reactive oxygen species; RSV: resveratrol; SIRT: sirtuin; TFAM: mitochondrial transcription factor A; TGF-β: transforming growth factor-β.