Galbanic acid of Ferula assa-foetida L, as a regulator of the AMPK pathway in reduction of lipid accumulation in HepG2 cells

Introduction: Hepatic fat accumulation is a complication of non-alcoholic fatty liver disease (NAFLD). An AMP-activated protein kinase (AMPK) reduces the synthesis of fatty acids by inhibiting sterol regulatory element-binding transcription factor 1-c (SREBP1-C) and acetyl COA carboxylase (ACC). Objectives: We aimed to investigate the impress of galbanic acid (Gal) from the Ferula plant on AMPK and its inhibitory effect on lipogenic enzymes in HepG2 cells. Materials and Methods: In an applied-fundamental study, HepG2 cells were treated for 24 hours with Gal in palmitate (Pal). Resveratrol (RSV) was conducted as a positive control. Fatty acid synthase (FAS) and SREBP1-C gene expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR). FAS, phospho-acetyl-CoA carboxylase (P-ACC), P-AMPK, AMPK, SREBP-1c, and ACC protein levels were measured by western blotting. Lipid accumulation was investigated qualitatively and semi-quantitatively with oil red. Results: The semi-quantitative results of oil revealed a substantial reduction (P<0.004) in lipid accumulation for treatment with Gal. The significant increase in the protein level of P-AMPK (P<0.001) and P-ACC (P=0.054) and significant decrease in FAS (P<0.003), SREBP-1c (P<0.001) and ACC (P<0.011) due to the effect galbanic acid was observed. FAS gene expression decreased significantly (P<0.009), while the decrease in SREBP-1c gene expression was not significant (P=0.303). Conclusion: These findings direct that galbanic acid can be a new regulator of AMPK. Hence, the present study may introduce galbanic acid as a new plan to positively regulate the AMPK pathway, which leads to the regulation of various cellular processes.