%0 Journal Article
%T A molecular and computational study of galbanic acid as a regulator of Sirtuin1 pathway in inhibiting lipid accumulation in HepG2 cells.
%A Musavi H
%A Shokri Afra H
%A Sadeghkhani F
%A Ghalehnoei H
%A Khonakdar-Tarsi A
%A Mahjoub S
%J Arch Physiol Biochem
%V 0
%N 0
%D 2024 May 7
%M 38712991
%F 3.188
%R 10.1080/13813455.2024.2336911
%X <B>UNASSIGNED: </B>Sirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro.<BR><B>UNASSIGNED: </B>HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns.<BR><B>UNASSIGNED: </B>The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar.<BR><B>UNASSIGNED: </B>Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.