, Volume 35, Issue 2, pp 197–203 | Cite as

Inhibition of cholesterol biosynthesis by organosulfur compounds derived from garlic

  • Lijuan Liu
  • Yu-Yan YehEmail author


The study was undertaken to test the inhibitory potential on cholesterogenesis of organosulfur compounds derived from garlic. The primary rat hepatocytes maintained in Dulbecco's modified Eagle's medium were treated with [2-14C]-acetate as substrate for cholesterol synthesis in the presence or absence of test compounds at 0.05 to 4.0 mmol/L. Eleven watersoluble and six lipid-soluble compounds of garlic were tested. Among water-soluble compounds,S-allyl cysteine (SAC),S-ethyl cysteine (SEC), andS-propyl cysteine (SPC) inhibited [2-14C]acetate incorporation into cholesterol in a concentration-dependnet manner, achieving 42 to 55% maximal inhibition. γ-Glutamyl-S-allyl cysteine, γ-glutamyl-S-methyl cysteine, and γ-glutamyl-S-propyl cysteine were less potent, exerting only 16 to 29% maximal inhibitions. Alliin,S-allyl-N-acetyl cysteine,S-allylsulfonyl alanine, andS-methyl cysteine had no effect on cholesterol synthesis. Of the lipid-soluble compounds, diallyl disulfide (DADS), diallyl trisulfide (DATS), and dipropyl disulfide (DPDS) depressed cholesterol synthesis by 10 to 25% at low concentrations (0.5 mmol/L), and abolished the synthesis at high concentrations (1.0 mmol/L). Diallyl sulfide, dipropyl sulfide, and methyl allyl sulfide slightly inhibited [2-14C]acetate incorporation into cholesterol only at high concentrations. The complete depression of cholesterol synthesis by DADS, DATS, and DPDS was associated with cytotoxicity as indicated by marked increase in cellular LDH release. There was no apparent increase in LDH secretion by water-soluble compounds exceptS-allyl mercaptocysteine, which also abolished cholesterol synthesis. Judging from maximal inhibition and IC50 (concentration required for 50% of maximal inhibition), SAC, SEC, and SPC are equally potent in inhibiting cholesterol synthesis.


Allicin Diallyl Organosulfur Compound Aged Garlic Extract Acetate Incorporation 
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.



analysis of variance


diallyl disulfide


diallyl sulfide


diallyl trisulfide


Dulbecco's modified Eagle's medium


dimethyl sulfoxide


dipropyl disulfide


dipropyl sulfide


fetal bovine serum


γ-glutamyl-S-allyl cysteine


γ-glutamyl-S-methyl cysteine


γ-glutamyl-S-propyl cysteine


concentration required for 50% of maximal inhibition


lactate dehydrogenase


methyl allyl sulfide




S-allyl cysteine


S-allyl mercaptocysteine


S-allyl-N-acetyl cysteine


S-allylsulfonyl alanine


S-ethyl cysteine


S-methyl cysteine


S-propyl cysteine


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Steiner, M., Khan, A.H., Holbert, D., and Lin, R.I. (1996) A Double-Blind Crossover Study in Moderately Hypercholesterolemic Men That Compared the Effect of Aged Garlic Extract and Placebo Administration on Blood Lipids,Am. J. Clin. Nutr. 64, 866–870.PubMedGoogle Scholar
  2. 2.
    Yeh, Y.-Y., Lin, R.I., Yeh, S.-M., and Evens, S. (1997) Garlic Reduces Plasma Cholesterol in Hypercholesterolemic Men Maintaining Habitual Diets, inFood Factors for Cancer Prevention (Ohigashi, H., Osawa, T., Terao, J., Watanabe, S., and Toshikawa, T., eds.), pp. 226–230, Springer, Tokyo.Google Scholar
  3. 3.
    Milner, J.A. (1996) Garlic: Its Anticarcinogenic and Antitumorigenic Properties,Nutr. Rev. 54, S82-S86.PubMedCrossRefGoogle Scholar
  4. 4.
    Dirsch, V.M., Gerbes, A.L., and Vollmar, A.M. (1998) Ajoene, a Compound of Garlic, Induces Apoptosis in Human Promyeloleukemic Cells, Accompanied by Generation of Reactive Oxygen Species and Activation of Nuclear Factor κB,Mol. Pharmacol. 53, 402–407.PubMedGoogle Scholar
  5. 5.
    Lin, X.Y., Liu, J.Z., and Milner, J.A. (1994) Dietary Garlic Suppresses DNA Adducts Caused byN-Nitroso Compounds,Carcinogenesis 15, 349–352.PubMedCrossRefGoogle Scholar
  6. 6.
    Sakamoto, K., Lawson, L.D., and Milner, J.A. (1997) Allyl Sulfides from Garlic Suppress thein vitro Proliferation of Human A549 Lung Tumor Cells,Nutr. Cancer 29, 152–156.PubMedGoogle Scholar
  7. 7.
    Schaffer, E.M., Liu, J.Z., Green, J., Dangler, C.A., and Milner, J.A. (1996) Garlic and Associated Allyl Sulfur Components InhibitN-Methyl-N-nitrosourea Induced Rat Mammary Carcinogenesis,Cancer Lett. 102, 199–204.PubMedCrossRefGoogle Scholar
  8. 8.
    Sundaram, S.G., and Milner, J.A. (1993) Impact of Organosulfur Compounds in Garlic on Canine Mammary Tumor Cells in Culture,Cancer Lett. 74, 85–90.PubMedCrossRefGoogle Scholar
  9. 9.
    Sundaram, S.G., and Milner, J.A. (1996) Diallyl Disulfide Inhibits the Proliferation of Human Tumor Cells in Culture,Biochim. Biophys. Acta 1315, 15–20.PubMedGoogle Scholar
  10. 10.
    Dion, M.E., Agler, M., and Milner, J.A. (1997)S-Allyl Cysteine Inhibits Nitrosomorpholine Formation and Bioactivation,Nutr. Cancer 28, 1–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Srivastava, S.K., Hu, X., Xia, H., Zaren, H.A., Chatterjee, M.L., Agarwal, R., and Singh, S.V. (1997) Mechanism of Differential Efficacy of Garlic Organosulfides in Preventing Benzo(a)-pyrene-Induced Cancer in Mice,Cancer Lett. 118, 61–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Auer, W., Eiber, A., Hertkorn, E., Hoehfeld, E., Koehrle, U., Lorenz, A., Mader, F., Merx, W., Otto, G., and Schmid-Otto, B. (1990) Hypertension and Hyperlipidaemia: Garlic Helps in Mild Cases,Br. J. Clin. Pract. Suppl. 69, 3–6.PubMedGoogle Scholar
  13. 13.
    Brosche, T., Platt, D., and Dorner, H. (1990) The Effect of a Garlic Preparation on the Composition of Plasma Lipoproteins and Erythrocyte Membranes in Geriatric Subjects,Br. J. Clin. Pract. Suppl. 69, 12–19.PubMedGoogle Scholar
  14. 14.
    Jain, A.K., Vargas, R., Gotzbowsky, S., and McMahon, F.G. (1993) Can Garlic Reduce Levels of Serum Lipids?Am. J. Med. 94, 632–635.PubMedCrossRefGoogle Scholar
  15. 15.
    Lau, B.H.S., Sam, F., and Wang-Cheng, R. (1987) Effect of an Odor-Modified Garlic Preparation on Blood Lipids,Nutr. Res. 7, 139–149.CrossRefGoogle Scholar
  16. 16.
    Qureshi, A.A., Abuirmeileh, N., Din, Z.Z., Elson, C.E., and Burger, W.C. (1983) Inhibition of Cholesterol and Fatty Acid Biosynthesis in Liver Enzymes and Chicken Hepatocytes by Polar Fractions of Garlic,Lipids 18, 343–348.PubMedCrossRefGoogle Scholar
  17. 17.
    Vorberg, G., and Schneider, B. (1990) Therapy with Garlic: Results of a Placebo-Controlled, Double-Blind Study,Br. J. Clin. Pract. Suppl. 69, 7–11.PubMedGoogle Scholar
  18. 18.
    Silagy, C., and Neil, A. (1994) Garlic as a Lipid Lowering Agent—A Meta-Analysis,J.R. Coll. Physicians Lond. 28, 39–45.PubMedGoogle Scholar
  19. 19.
    Warshafsky, S., Kamer, R.S., and Sivak, S.L. (1993) Effect of Garlic on Total Serum Cholesterol. A Meta-Analysis,Ann. Intern. Med. 119, 599–605.PubMedGoogle Scholar
  20. 20.
    Bordia, A., Verma, S.K., and Srivastava, K.C. (1998) Effect of Garlic (Allium sativum) on Blood Lipids, Blood Sugar, Fibrinogen and Fibrinolytic Activity in Patients with Coronary Artery Disease,Prostaglandins Leukotrienes Essent. Fatty Acids 58, 257–263.CrossRefGoogle Scholar
  21. 21.
    Berthold, H.K., Sudhop, T., and von Bergmann, K. (1998) Effect of a Garlic Oil Preparation on Serum Lipoproteins and Cholesterol Metabolism: A Randomized Controlled Trial,JAMA 279, 1900–1902.PubMedCrossRefGoogle Scholar
  22. 22.
    Isaacsohn, J.L., Moser, M., Stein, E.A., Dudley, K., Davey, J.A., Liskov, E., and Black, H.R. (1998) Garlic Powder and Plasma Lipids and Lipoproteins: A Multicenter, Randomized, Placebo-Controlled Trial,Arch. Intern. Med. 158, 1189–1194.PubMedCrossRefGoogle Scholar
  23. 23.
    Simons, L.A., Balasubramaniam, S., von Konigsmark, M., Parfitt, A., Simons, J., and Peters, W. (1995) On the Effect of Garlic on Plasma Lipids and Lipoproteins in Mild Hypercholesterolaemia,Atherosclerosis 113, 219–225.PubMedCrossRefGoogle Scholar
  24. 24.
    Gebhardt, R. (1991) Inhibition of Cholesterol Biosynthesis by a Water-Soluble Garlic Extract in Primary Cultures of Rat Hepatocytes,Arzneim. Forsch. 41, 800–804.Google Scholar
  25. 25.
    Gebhardt, R. (1993) Multiple Inhibitory Effects of Garlic Extracts on Cholesterol Biosynthesis in Hepatocytes,Lipids 28, 613–619.PubMedCrossRefGoogle Scholar
  26. 26.
    Gebhardt, R., Beck, H., and Wagner, K.G. (1994) Inhibition of Cholesterol Biosynthesis by Allicin and Ajoene in Rat Hepatocytes and HepG2 Cells,Biochim. Biophys. Acta 1213, 57–62.PubMedGoogle Scholar
  27. 27.
    Yeh, Y.-Y., and Yeh, S.-M. (1994) Garlic Reduces Plasma Lipids by Inhibiting Hepatic Cholesterol and Triacylglycerol Synthesis,Lipids 29, 189–193.PubMedCrossRefGoogle Scholar
  28. 28.
    Gebhardt, R., and Beck, H. (1996) Differential Inhibitory Effects of Garlic-Derived Organosulfur Compounds on Cholesterol Biosynthesisin Primary Rat Hepatocyte Cultures,Lipids 31, 1269–1276.PubMedCrossRefGoogle Scholar
  29. 29.
    Lawson, L.D. (1993) Bioactive Organosulfur Compounds of Garlic and Garlic Products, inHuman Medicinal Agents from Plants (Kinghorn, A.D., and Balandrin, M.F., eds.), pp. 307–330, American Chemical Society, Washington, DC.Google Scholar
  30. 30.
    Agarwal, K.C. (1996) Therapeutic Actions of Garlic Constituents,Med. Res. Rev. 16, 111–124.PubMedCrossRefGoogle Scholar
  31. 31.
    Berry, M.N., and Friend, D.S. (1969) High-Yield Preparation of Isolated Rat Liver Parenchymal Cells: A Biochemical and Fine Structural Study,J. Cell Biol. 43, 506–520.PubMedCrossRefGoogle Scholar
  32. 32.
    Seglen, P.O. (1973) Preparation of Rat Liver Cells. 3. Enzymatic Requirements for Tissue Dispersion,Exp. Cell Res. 82, 391–398.PubMedCrossRefGoogle Scholar
  33. 33.
    Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues,J. Biol. Chem. 226, 497–510.PubMedGoogle Scholar
  34. 34.
    Kabara, J.J. (1957) A Quantitative Micromethod for Isolation and Liquid Scintillation Assay of Radioactive Free and Ester Cholesterol,J. Lab. Clin. Med. 50, 146–151.PubMedGoogle Scholar
  35. 35.
    Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randall, R.J. (1951) Protein Measurement with the Folin Phenol Reagent,J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  36. 36.
    Chao, E.S., Dunbar, D., and Kaminsky, L.S. (1988) Intracellular Lactate Dehydrogenase Concentration as an Index of Cytotoxicity in Rat Hepatocyte Primary Culture,Cell Biol. Toxicol. 4, 1–11.PubMedCrossRefGoogle Scholar
  37. 37.
    Jauregui, H., Hayner, N.T., Driscoll, J.L., Williams-Holland, R., Lipsky, M.H., and Galletti, P.M. (1981) Trypan Blue Dye Uptake and Lactate Dehydrogenase in Adult Rat Hepatocytes—Freshly Isolated Cells, Cell Suspensions, and Primary Monolayer Cultures,In Vitro 81, 1100–1110.CrossRefGoogle Scholar
  38. 38.
    Houck, H.E., Lipsky, M.M., Marzella, L., and Burnett, J.V. (1996) Toxicity of Sea Nettle (Chrysaora quinquecirrha) Fishing Tentacle Nematocyst Venom in Cultured Rat Hepatocytes,Toxicon 34, 771–778.PubMedCrossRefGoogle Scholar
  39. 39.
    McMillan, J.M., and Jollow, D.J. (1995) Macrophage Enhancement of Galactosamine Hepatotoxicity Using a Rat Hepatocyte Culture System,Res. Commun. Mol. Pathol. Pharmacol. 88, 327–338.PubMedGoogle Scholar
  40. 40.
    Zurlo, J., and Arterburn, L.M. (1996) Characterization of a Primary Hepatocyte Culture System for Toxicological Studies,In Vitro Cell Dev. Biol. 32, 211–220.Google Scholar
  41. 41.
    Abdul-Hussain, S.K., and Mehendale, H.M. (1991) Studies on the Age-Dependent Effects of Galactosamine in Primary Rat Hepatocyte Cultures,Toxicol. Appl. Pharmacol. 107, 504–513.PubMedCrossRefGoogle Scholar
  42. 42.
    Augusti, K.T. (1996) Therapeutic Values of Onion (Allium cepa L.) and Garlic (Allium sativum L.),Indian J. Exp. Biol. 34, 634–640.PubMedGoogle Scholar
  43. 43.
    Imai, J., Ide, N., Nagae, S., Moriguchi, T., Matsuura, H., and Itakura, Y. (1994) Antioxidant and Radical Scavenging Effects of Aged Garlic Extract and Its Constituents,Planta Med. 60, 417–420.PubMedCrossRefGoogle Scholar
  44. 44.
    Amagase, H., and Milner, J.A. (1993) Impact of Various Sources of Garlic and Their Constituents on 7,12-Dimethylbenz[a]anthracene Binding to Mammary Cell DNA,Carcinogenesis 14, 1627–1631.PubMedCrossRefGoogle Scholar
  45. 45.
    Qureshi, A.A., Crenshaw, T.D., Abuirmeileh, N., Peterson, D.M., and Elson, C.E. (1987) Influence of Minor Plant Constituents on Porcine Hepatic Lipid Metabolism. Impact on Serum Lipids,Atherosclerosis 64, 109–115.PubMedCrossRefGoogle Scholar
  46. 46.
    Focke, M., Feld, A., and Lichtenthaler, K. (1990) Allicin, a Naturally Occurring Antibiotic from Garlic, Specifically Inhibits Acetyl-CoA Synthetase,FEBS Lett. 261, 106–108.PubMedCrossRefGoogle Scholar

Copyright information

© AOCS Press 2000

Authors and Affiliations

  1. 1.Graduate Program in NutritionThe Pennsylvania State UniversityUniversity Park

Personalised recommendations