The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells

Non-alcoholic fatty liver disease (NAFLD) results from fat accumulation in the liver (liver fat >5% of liver
weight). The excess of lipids in hepatic steatosis primarily consists of triacylglycerol and cholesterol esters. De novo hepatic lipogenesis
from excessive dietary carbohydrate intake is the most consistent underlying pathogenic agent of NAFLD. Hypercholesterolemia that
mostly associates with NAFLD has been recognized as the most important risk factor for the development of coronary heart disease
(CHD). In other words, reducing the hepatic cholesterol synthesis in NAFLD patients prevents risk of developing atherosclerosis and
CHD. HMGCR is the rate-controlling enzyme pathway, responsible for cholesterol biosynthesis. De novo cholesterol synthesis by
inducing the expression of HMGCR; activates the SREBP2. PPARα activation significantly lowers hepatic SREBP2 and HMGR
mRNA levels. The aim of this study was to investigate the effect of Fenofibrate and Biochanin A, as PPARα agonists, on mRNA levels
of SREBP2 and HMGR in HepG2 cells exposed to high glucose concentration.HepG2 cells were used in this study. The induction of steatosis was performed by high glucose concentration.
Cytotoxicity of Glucose, Fenofibrate, and Biochanin A were assessed in separate experiments for HepG2 cells. Some biochemical
parameters such as intracellular total cholesterol, HMGCR, ALT, and AST activity were measured. SREBP2 and HMGR mRNA levels
were examined by real-time RT-PCR.
Results: Results of our study indicated an inhibitory effect of Fenofibrate and Biochanin A on the mRNA levels of SREBP2 and HMGR
in HepG2 cells which were treated by high glucose concentration. Additionally, a decreased level of intracellular total cholesterol
concentration was accompanied by decreased HMGCR activity.
Conclusion: Based on the findings of the present study, it can be concluded that Biochanin A could be a useful agent in the prevention
of de novo hepatic cholesterol synthesis and development of hypercholesterolemia; which is the main cause of CHD.