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Lipids

, Volume 28, Issue 7, pp 613–619 | Cite as

Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes

  • Rolf Gebhardt
Article

Abstract

Exposure of primary rat hepatocytes and human HepG2 cells to water-soluble garlic extracts resulted in the concentration-dependent inhibition of cholesterol biosynthesis at several different enzymatic steps. At low concentrations, sterol biosynthesis from [14C]acetate was decreased in rat hepatocytes by 23% with an IC50 (half-maximal inhibition) value of 90μg/mL and in HepG2 cells by 28% with an IC50 value of 35 μg/mL. This inhibition was exerted at the level of hydroxymethylglutaryl-COA reductase (MHG-CoA reductase) as indicated by direct enzymatic measurements and the absence of inhibition if [14C]mevalonate was used as a precursor. At high concentrations (above 0.5 mg/mL), inhibition of cholesterol biosynthesis was not only seen at an early step where it increased considerably with dose, but also at later steps resulting in the accumulation of the precursors lanosterol and 7-dehydrocholesterol. No desmosterol was formed which, however, was a major precursor accumulating in the presence of triparanol. Thus, the accumulation of sterol precursors seem to be of less therapeutic significance during consumption of garlic, because it requires concentrations one or two orders of magnitude above those affecting HMG-CoA reductase. Alliin, the main sulfur-containing compound of garlic, was without effect itself. If converted to allicin, it resulted in similar changes of the sterol pattern. This suggested that the latter compound might contribute to the inhibition at the late steps. In contrast, nicotinic acid and particularly adenosine caused moderate inhibition of HMG-CoA reductase activity and of cholesterol biosynthesis suggesting that these compounds participate, at least in part, in the early inhibition of sterol synthesis by garlic extracts.

Keywords

HepG2 Cell Mevalonate Cholesterol Biosynthesis Lanosterol Allicin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

HMG-CoA reductase

hydroxymethylglutaryl-CoA reductase (EC 1.1.1.34)

IC50

the concentration for half-maximal inhibition

LDH

lactate dehydrogenase (EC 1.1.1.27)

SI-TLC

silverion thin-layer chromatography

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Copyright information

© American Oil Chemists’ Society 1993

Authors and Affiliations

  • Rolf Gebhardt
    • 1
  1. 1.Physiologisch-Chemisches InstituteUniversity of TübingenTübingenGermany

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