Hypolipidemic effects of silymarin are not mediated by the peroxisome proliferator-activated receptor alpha

Abstract

Silymarin is widely used in supportive therapy of liver diseases. It has been shown lately that silymarin has beneficial effects on some risk factors of atherosclerosis owing to its hypolipidemic properties. PPARα plays a key role in lipid metabolism and homeostasis as its target genes are involved in catabolism of fatty acids by β-oxidation (e.g. acyl-CoA oxidase) and by ω-oxidation (e.g. cytochrome P4504A). Here we studied the possibility that hypolipidemic effects of silymarin may be mediated by PPARα. Rats fed with a high-cholesterol diet with either silymarin or fenofibrate (as a positive control both for PPARα expression as well as for lipid determination) were used. The effects of silymarin on expression of PPARα both at the mRNA (including selected target genes) as well as the protein level were determined. In parallel, the levels of cholesterol and triacylglycerols were determined. Our results confirmed the hypolipidemic effects of silymarin and demonstrated that these effects are probably not mediated by PPARα because of unchanged mRNA levels of PPARα target genes. Furthermore, this work shows for the first time that cholesterol itself inhibits expression of CYP4A mRNA.

Key Words::

• Silymarin
• PPARα
• Cholesterol
• Cytochrome P4504A

Acknowledgements

This project was covered in part by the COST B25.003 project and by Czech Ministry of Education grants 1P03OC065 and MSM 6198959216. Professor Meyer's laboratory is supported by Swiss National Science Foundation.