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Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes.
Lipids. 1993 Jul; 28(7):613-9.L

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 90 micrograms/mL and in HepG2 cells by 28% with an IC50 value of 35 micrograms/mL. This inhibition was exerted at the level of hydroxymethylglutaryl-CoA reductase (HMG-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 seems 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.

Authors+Show Affiliations

Physiologisch-Chemisches Institut, University of Tübingen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8394977

Citation

Gebhardt, R. "Multiple Inhibitory Effects of Garlic Extracts On Cholesterol Biosynthesis in Hepatocytes." Lipids, vol. 28, no. 7, 1993, pp. 613-9.
Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids. 1993;28(7):613-9.
Gebhardt, R. (1993). Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. Lipids, 28(7), 613-9.
Gebhardt R. Multiple Inhibitory Effects of Garlic Extracts On Cholesterol Biosynthesis in Hepatocytes. Lipids. 1993;28(7):613-9. PubMed PMID: 8394977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes. A1 - Gebhardt,R, PY - 1993/7/1/pubmed PY - 1993/7/1/medline PY - 1993/7/1/entrez SP - 613 EP - 9 JF - Lipids JO - Lipids VL - 28 IS - 7 N2 - 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 90 micrograms/mL and in HepG2 cells by 28% with an IC50 value of 35 micrograms/mL. This inhibition was exerted at the level of hydroxymethylglutaryl-CoA reductase (HMG-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 seems 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. SN - 0024-4201 UR - https://www.unboundmedicine.com/medline/citation/8394977/Multiple_inhibitory_effects_of_garlic_extracts_on_cholesterol_biosynthesis_in_hepatocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0024-4201&date=1993&volume=28&issue=7&spage=613 DB - PRIME DP - Unbound Medicine ER -