The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells
Background & Aims: 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...
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| Format: | Article |
| Language: | English |
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Urmia University of Medical Sciences
2020-06-01
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| Series: | Journal of Research in Applied and Basic Medical Sciences |
| Subjects: | |
| Online Access: | http://ijrabms.umsu.ac.ir/article-1-118-en.pdf |
| _version_ | 1827865813533589504 |
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| author | Negar Karimi Darya Ghadimi Mojtaba Fathi |
| author_facet | Negar Karimi Darya Ghadimi Mojtaba Fathi |
| author_sort | Negar Karimi |
| collection | DOAJ |
| description | Background & Aims: 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.
Materials & Methods: 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 |
| first_indexed | 2024-03-12T14:54:38Z |
| format | Article |
| id | doaj.art-698cc93b9b484865b842ae445d56443e |
| institution | Directory Open Access Journal |
| issn | 2717-0098 |
| language | English |
| last_indexed | 2024-03-12T14:54:38Z |
| publishDate | 2020-06-01 |
| publisher | Urmia University of Medical Sciences |
| record_format | Article |
| series | Journal of Research in Applied and Basic Medical Sciences |
| spelling | doaj.art-698cc93b9b484865b842ae445d56443e2023-08-15T04:45:55ZengUrmia University of Medical SciencesJournal of Research in Applied and Basic Medical Sciences2717-00982020-06-0163167185The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 CellsNegar Karimi0Darya Ghadimi1Mojtaba Fathi2 Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences Background & Aims: 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. Materials & Methods: 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 CHDhttp://ijrabms.umsu.ac.ir/article-1-118-en.pdfnafldsrebp2hmg-coa reductasebiochanin afenofibrate |
| spellingShingle | Negar Karimi Darya Ghadimi Mojtaba Fathi The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells Journal of Research in Applied and Basic Medical Sciences nafld srebp2 hmg-coa reductase biochanin a fenofibrate |
| title | The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells |
| title_full | The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells |
| title_fullStr | The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells |
| title_full_unstemmed | The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells |
| title_short | The Inhibitory Effect of Biochanin A on Hepatic Cholesterol Biosynthesis in High Glucose-Induced Steatosis in HepG2 Cells |
| title_sort | inhibitory effect of biochanin a on hepatic cholesterol biosynthesis in high glucose induced steatosis in hepg2 cells |
| topic | nafld srebp2 hmg-coa reductase biochanin a fenofibrate |
| url | http://ijrabms.umsu.ac.ir/article-1-118-en.pdf |
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