Effect of Genistein on Cholesterol Metabolism‐Related Genes in HepG2 Cell

• Published in: Journal of food science 2019-08, Vol.84 (8), p.2330-2336
• Main Authors: Lu, Rongrong, Zheng, Zicong, Yin, Yimin, Jiang, Zhuoqin
• Format: Article
• Language: English
• Subjects: ABCA1 protein; Absorption; Apolipoproteins; Arteriosclerosis; Atherosclerosis; ATP-binding protein; Binding; Cholesterol; Coenzyme A; Density; Dosage; Efflux; Genistein; High density lipoprotein; Hydroxymethylglutaryl-CoA reductase; Intracellular; Lipid metabolism; Liver X receptors; Low density lipoprotein receptors; Metabolic disorders; Metabolism; mRNA; peroxisome proliferator‐activated receptor‐γ; Protein transport; Proteins; Receptor density; Reductases; Regulatory sequences; Secretion; sterol regulatory element binding proteins‐2; Sterol regulatory element-binding protein
• ISSN: 0022-1147; 1750-3841
• DOI: 10.1111/1750-3841.14725

It has been reported that genistein could improve metabolic syndromes. Our study aimed to investigate the effects and potential mechanisms of genistein on improving cholesterol metabolism in HepG2 cell. HepG2 cells were cultured with 0, 0.01, 1.00, 10.00, and 50.00 µM genistein for 24 hr. The current results showed a dose‐dependent manner between genistein and intracellular contents of total cholesterol (TC), high‐density lipoprotein‐cholesterol (HDL‐C), and cellular apolipoprotein A1 (Apo‐A1) secretion. TC was increased by 25.69%, meanwhile HDL‐C and Apo‐A1 were decreased by 56.00% and 25.93%, respectively, when the dosage of genistein was 1.00 µM. Genistein dose‐dependently upregulated the protein and mRNA levels of sterol regulatory element binding proteins‐2 (SREBP‐2), as well as the mRNA levels of low‐density lipoprotein receptor (LDLR) and 3‐hydroxy‐3‐methyl glutaryl coenzyme A reductase (HMGCR), by 145.91%, 72.29%, 310.23%, and 123.08%, respectively, when we gave 1.00 µM genistein, indicating that intracellular cholesterol synthesis and absorption of exogenous cholesterol were increased. In addition, the mRNA levels of peroxisome proliferator‐activated receptor‐γ (PPARγ) and liver X receptor (LXRα), lowered by 58.23% and 34.86% at 0.01 µM genistein, were reduced in a dose‐dependent manner. LXRα and ATP‐binding cassette transporter A1 (ABCA1) protein levels were significantly (P < 0.05) decreased by 50.35% and 11.60% at 1.00 µM genistein, which indicated that cellular cholesterol efflux was inhibited. Taken together, our results suggested that genistein at dosage of more than 1.00 µM was able to increase the intracellular cholesterol levels by up regulating SREBP‐2/LDLR/HMGCR pathway and suppressing PPARγ/LXRα/ABCA1 pathway. Practical Application In this study, genistein appeared to be effective in reducing plasma cholesterol levels due to increase the intracellular cholesterol levels by upregulating cholesterol absorption through SREBP‐2/LDLR/HMGCR pathway, and also downregulating cholesterol efflux via PPARγ/LXRα/ABCA1 pathway in vitro. In addition, plasma cholesterol is regarded as the key indicator of atherosclerosis; therefore, we believe that our findings could be used for further exploration on a possible therapeutic application of genistein for atherosclerosis.