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Cholestin inhibits cholesterol synthesis and secretion in hepatic cells (HepG2)
Ricky Y K Man1, Edward G Lynn, Filly Cheung
1Department of Pharmacology, Faculty of Medicine, University of Hong Kong, China.
Insights
Cholestin, a red yeast rice supplement, inhibits cholesterol synthesis in liver cells by reducing HMG-CoA reductase activity. This natural alternative offers a potential treatment for hyperlipidemia by lowering cholesterol levels.
Area of Science:
- Biochemistry
- Pharmacology
- Nutraceuticals
Background:
- Hyperlipidemia is a significant risk factor for atherosclerosis.
- Statins are primary treatments for hyperlipidemia but have limitations like cost and side effects.
- Natural products offer potential alternatives for managing lipid levels.
Purpose of the Study:
- To investigate the cellular effects of Cholestin on cholesterol synthesis in human hepatic cells (HepG2).
- To elucidate the mechanism of action of Cholestin in altering lipid metabolism.
- To document the biomolecular action of red yeast rice.
Main Methods:
- Treatment of HepG2 cells with varying concentrations of Cholestin.
- Assay of HMG-CoA reductase activity.
- Quantification of cellular and secreted cholesterol and cholesteryl ester levels.
Main Results:
- Cholestin significantly inhibited HMG-CoA reductase activity (78-69% reduction).
- Cholesterol levels in HepG2 cells decreased dose-dependently (81-45% reduction).
- Synthesis and secretion of unesterified cholesterol and cholesteryl ester were reduced.
Conclusions:
- Cholestin exerts anti-hyperlipidemic effects by inhibiting cholesterol biosynthesis in hepatic cells.
- This study provides the first documentation of the biomolecular mechanism of red yeast rice.
- Cholestin represents a potential natural alternative for managing hyperlipidemia.
Abstract:
Hyperlipidemia is a well-known risk factor for atherosclerosis and statins are widely used to treat patients with elevated levels of lipids in their plasma. Notwithstanding the proven benefits of statin drugs on both primary and secondary prevention of heart disease, the high cost of statin treatment, in addition to possible side effects such as liver function abnormalities, may limit their widespread use. We conducted a study on a natural product as an alternative to statin treatment. Cholestin, a dietary supplement, is prepared from rice fermented with red yeast (Monascus purpureus), which has been shown to significantly decrease total cholesterol levels in hyperlipidemic subjects. Our objective was to determine the cellular effect of Cholestin on cholesterol synthesis in human hepatic cells (HepG2) and the mechanism by which it caused a change in lipid metabolism. Cholestin had a direct inhibitory effect on HMG-CoA reductase activity (78-69% of control). Cholesterol levels in HepG2 cells treated with Cholestin (25-100 microg/mL) were significantly reduced in a dose-dependent manner (81-45% of control, respectively). This reduction was associated with decreased synthesis and secretion of both unesterified cholesterol (54-31 and 33-14% of control, respectively) and cholesteryl ester (18-6 and 37-19% of control, respectively). These results indicate that one of the anti-hyperlipidemic actions of Cholestin is a consequence of an inhibitory effect on cholesterol biosynthesis in hepatic cells and provide the first documentation of a biomolecular action of red yeast rice.