Berberine inhibits sirtuins at transcriptional as well as at translational level.
Sirtuins inhibition leads to acetylation of non-histone proteins, FoxO1/3a and p53.
Acetylated FoxO and p53 transcriptionally upregulate BH3-only proteins Bim and PUMA respectively.
BH3-only proteins trigger mitochondrial dysfunction culminating into apoptosis.
SRT-1720 (SIRT-1 activator) partially restores Bax/Bcl-2 ratio and reduces berberine induced cytotoxicity in HepG2 cells.