Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells.

Exposure of primary rat hepatocytes and human HepG2 cells to allicin and ajoene resulted in the concentration-dependent inhibition of cholesterol biosynthesis at different steps of this metabolic pathway. At low concentrations of ajoene sterol biosynthesis from [14C]acetate in rat hepatocytes was decreased by 18% with an IC50-value of 15 microM, while allicin was almost uneffective. In HepG2 cells, both compounds significantly inhibited sterol biosynthesis by 14% and 19% with IC50-values of 7 and 9 microM for allicin and ajoene, respectively. This inhibition was exerted at the level of HMG-CoA-reductase as revealed by the absence of inhibition, if [14C]acetate was replaced by [14C]mevalonate as a precursor, and by direct determination of enzyme activity. At somewhat higher concentrations inhibition of cholesterol biosynthesis by both, allicin and ajoene, was also observed at late steps resulting in the accumulation of the precursor lanosterol. Alliin instead was completely inactive. In the case of allicin, small amounts of dihydrolanosterol and 7-dehydrocholesterol were formed at intermediate concentrations of 5-10 microM. From these results it is concluded that a major point of inhibition at the late steps occurs at the level of lanosterol 14 alpha-demethylase.