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

Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes

  • Rolf Gebhardt


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.


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.


HMG-CoA reductase

hydroxymethylglutaryl-CoA reductase (EC


the concentration for half-maximal inhibition


lactate dehydrogenase (EC


silverion thin-layer chromatography


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  1. 1.
    Augusti, K.T., and Mathew, P.T. (1973)Ind. J. Exp. Biol. 11, 239–241.Google Scholar
  2. 2.
    Jain, R.C. (1975)Artery 1, 115–125.Google Scholar
  3. 3.
    Jain, R.C., and Vyas, C.R. (1975)Artery 1, 363–364.Google Scholar
  4. 4.
    Reuter, H.D. (1988) inArzneimitteltherapie heute (Berufsverband Deutscher Internisten, ed.) Vol. 1, pp. 13–64, Aesopus Verlag, Zug.Google Scholar
  5. 5.
    Mader, F.H. (1990)Arzneim-Forsch/Drug. Res. 40, 1111–1116.Google Scholar
  6. 6.
    Vorberg, G., and Schneider, B. (1990)Br. J. Clin. Practice 44 (Suppl. 69, 7–11.Google Scholar
  7. 7.
    Davis, R.A., Engelhorn, S.C., Pangburn, S.H., Weinstein, D.B., and Steinberg, D. (1979)J. Biol. Chem. 254, 2010–2016.PubMedGoogle Scholar
  8. 8.
    Havel, C., Hansbury, E., Scallen, T.J., and Watson, J.A. (1979)J. Biol. Chem. 254, 9573–9582.PubMedGoogle Scholar
  9. 9.
    Bell-Quint, J., and Forte, T. (1981)Biochim. Biophys. Acta 663, 83–98.PubMedGoogle Scholar
  10. 10.
    Aufenanger, J., Pill, J., Schmidt, F.H., and Stegmeier, K. (1986)Biochem. Pharmacol. 35, 911–916.PubMedCrossRefGoogle Scholar
  11. 11.
    Gebhardt, R. (1986) inResearch in Isolated and Cultured Hepatocytes (Guguen-Guillouzo, C., and Guillouzo, A., eds.) pp. 353–375, John Libbey Eurotex, London, INSERM, Paris.Google Scholar
  12. 12.
    De La Vaga, F.M., and Mendoza-Figueroa, T. (1991)Biochim. Biophys. Acta 1081, 293–300.Google Scholar
  13. 13.
    Ugele, B., Kempen, H.J.M., Gebhardt, R., Meijer, P., Burger, H.-J., and Princen, H.M.G. (1991)Biochem. J. 276, 73–77.PubMedGoogle Scholar
  14. 14.
    Kempen, H.J., Van Son, K., Cohen, L.H., Griffioen, M., Verboom, H., and Havekes, L. (1987)Biochem. Pharmacol. 36, 1245–1249.PubMedCrossRefGoogle Scholar
  15. 15.
    Boogaard, A., Griffioen, M., and Cohen, L.H. (1987)Biochem. J. 241, 345–351.PubMedGoogle Scholar
  16. 16.
    Ranganathan, S., and Kottke, B.A. (1989)Hepatology 9, 547–551.PubMedGoogle Scholar
  17. 17.
    Gebhardt, R. (1991)Arzneim-Forsch/Drug Res. 41, 800–804.Google Scholar
  18. 18.
    Müller, B. (1989)Dtsch. Apoth. Ztg. 46, 2500–2504.Google Scholar
  19. 19.
    Iberl, B., Winkler, G., Müller, B., and Knobloch, K. (1990)Planta Med. 56, 320–326.Google Scholar
  20. 20.
    Gebhardt, R., Fitzke, H., Fausel, M., Eisenmann-Tappe, I., and Mecke, D. (1990)Cell Biol. Toxicol. 6, 365–378.PubMedCrossRefGoogle Scholar
  21. 21.
    Gebhardt, R., and Jung, W. (1982)J. Cell Sci. 56, 233–244.PubMedGoogle Scholar
  22. 22.
    Fahrner, J., Labruyere, W.T., Gaunitz, C., Moorman, A.F.M., Gebhardt, R., and Lamers, W.H. (1993)Eur. J. Biochem. 213, 1067–1073.PubMedCrossRefGoogle Scholar
  23. 23.
    Pill, J., Aufenanger, J., Stegmeier, K., Schmidt, F.H., and Müller, D. (1987)Fresenius Z. Anal. Chem. 327, 558–560.CrossRefGoogle Scholar
  24. 24.
    Shapiro, D.J., Nordstrom, J.L., Mitchelen, J.J., Rodwell, J.W., and Schimke, R.T. (1974)Biochim. Biophys. Acta 370, 369–377.PubMedGoogle Scholar
  25. 25.
    Nepokroeff, C.M., Lakshmanan, M.R., and Porter, J.W. (1975)Methods Enzymol. 35, 37–44.PubMedGoogle Scholar
  26. 26.
    Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951)J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  27. 27.
    Gebhardt, R. (1991)Medwelt 42 (Suppl. 7a), 12–13.Google Scholar
  28. 28.
    Qureshi, A.A., Abuirmeileh, N., Din, Z.Z., Elson, C.E., and Burger, W.C. (1983)Lipids 18, 343–348.PubMedGoogle Scholar
  29. 29.
    Koch, H.P., and Hahn, G. (1988)Knoblauch, pp. 42–72, Urban & Schwarzenberg München.Google Scholar
  30. 30.
    Glover, J., and Green, C. (1957)Biochem. J. 67, 308–316.PubMedGoogle Scholar
  31. 31.
    Van-den-Bossche, H., Willemsens, G., Cools, W., Cornelissen, F., Lauwers, W.F., and Van-Cutsem, J.M. (1980)Antimicrob. Agents. Chemother. 17, 922–928.PubMedGoogle Scholar
  32. 32.
    Horton, B.J., Horton, J.D., and Sabine, J.R. (1971)Biochim Biophys. Acta 239, 475–481.PubMedGoogle Scholar
  33. 33.
    Avigan, J., Steinberg, D., Vroman, H.E., Thompson, M.J., and Mosettig, E. (1960)J. Biol. Chem. 235, 3123–3126.PubMedGoogle Scholar
  34. 34.
    Goh, E.H., Colles, S.M., and Otte, K.D. (1989)Lipids 24, 652–655.PubMedCrossRefGoogle Scholar

Copyright information

© American Oil Chemists’ Society 1993

Authors and Affiliations

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

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