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Vol. 72, No. 6, 2005
Issue release date: April 2006
Pathobiology 2005;72:325–334

The Antiatherogenic Effect of Allicin: Possible Mode of Action

Gonen A. · Harats D. · Rabinkov A. · Miron T. · Mirelman D. · Wilchek M. · Weiner L. · Ulman E. · Levkovitz H. · Ben-Shushan D. · Shaish A.
aInstitute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel Hashomer, bSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, and cDepartment of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel

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Objective: Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. Methods and Results: Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO4-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with 3H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu2+ binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. Conclusions: By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages.

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  1. Lusis AJ: Atherosclerosis. Nature 2000;407:233–241.
  2. Glass CK, Witztum JL: Atherosclerosis: the road ahead. Cell 2001;104:503–516.
  3. Stocker R, Keaney JF: Role of oxidative modifications in atherosclerosis. Physiol Rev 2004;84:1381–1478.
  4. Parthasarathy S, Santanam N, Ramachandran S, Meilhac O: Oxidants and antioxidants in atherogenesis. An appraisal. J Lipid Res 1999;40:2143–2157.
  5. Diaz MN, Frei B, Vita JA, Keaney JF: Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408–416.
  6. Ferguson E, Singh RJ, Hogg N, Kalyanaraman B: The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low density lipoprotein. Arch Biochem Biophys 1997;341:287–294.
  7. Roland A, Patterson RA, Leake DS: Measurement of copper-binding sites on low density lipoprotein. Arterioscler Thromb Vasc Biol 2001;21:594–602.
  8. Jessup W, Kritharides L: Metabolism of oxidized LDL by macrophages. Curr Opin Lipidol 2000;11:473–481.
  9. Wang X, Greilberger J, Ledinski G, Kager G, Jurgens G: Binding and uptake of differently oxidized low density lipoprotein in mouse peritoneal macrophages and THP-1 macrophages: involvement of negative charges as well as oxidation-specific epitopes. J Cell Biochem 2001;81:557–569.
  10. Chait A, Heinecke JW: Lipoprotein modification: cellular mechanisms. Curr Opin Lipidol 1994;5:365–370.
  11. Burkitt MJ: A critical overview of the chemistry of copper-dependent low density lipoprotein oxidation: roles of lipid hydroperoxides, alpha-tocopherol, thiols, and cerulo plasmin. Arch Biochem Biophys 2001;394:117–135.
  12. Ackermann R, Mulrow C, Ramirez G, Gardner C, Morbidoni L, Lawrence V: Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813–824.
  13. Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H, Itakura Y: Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med 1994;60:417–420.
  14. Ali M, Al-Qattan KK, Al-Enezi F, Khanafer RM, Mustafa T: Effect of allicin from garlic powder on serum lipids and blood pressure in rats fed with a high cholesterol diet. Prostaglandins Leukot Essent Fatty Acids 2000;62:253–259.
  15. Campbell JH, Efendy JL, Smith NJ, Camp- bell GR: Molecular basis by which garlic suppresses atherosclerosis. J Nutr 2001;131:1006S–1009S.
  16. Eilat S, Oestraicher Y, Rabinkov A, Ohad D, Mirelman D, Battler A, Eldar M, Vered Z: Alteration of lipid profile in hyperlipidemic rabbits by allicin, an active constituent of garlic. Coronary Artery Dis 1995;6:985–990.
  17. Kwon MJ, Song YS, Choi MS, Park SJ, Jeong KS, Song YO: Cholesteryl ester transfer protein activity and atherogenic parameters in rabbits supplemented with cholesterol and garlic powder. Life Sci 2003;72:2953–2964.
  18. Munday JS, James KA, Fray LM, Kirkwood SW, Thompson KG: Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 1999;143:399–404.
  19. Dillon SA, Burmi RS, Lowe GM, Billington D, Rahman K: Antioxidant properties of aged garlic extract: an in vitro study incorporating human low density lipoprotein. Life Sci 2003;72:2953–2964.
  20. Brace LD: Cardiovascular benefits of garlic (Allium sativum L). J Cardiovasc Nurs 2002;16:33–49.

    External Resources

  21. Orekhov AN, Grunwald J: Effects of garlic on atherosclerosis. Nutrition 1997;13:656–663.
  22. Banerjee SK, Maulik SK: Effect of garlic on cardiovascular disorder: a review. Nutrition J 2002;1:1–14.

    External Resources

  23. Efendy JL, Simmons DL, Campbell GR, Campbell JH: The effect of the aged garlic extract, ‘Kyolic’, on the development of experimental atherosclerosis. Atherosclerosis 1997;132:37–42.
  24. Abramovitz D, Gavri S, Harats D, Levkovitz H, Mirelman D, Miron T, Eilat-Adar S, Rabinkov A, Wilchek M, Eldar M, Vered Z: Allicin-induced decrease in formation of fatty steaks (atherosclerosis) in mice fed on a cholesterol-rich diet. Coronary Artery Dis 1999;10:515–519.
  25. Prasad K, Laxdal VA, Yu M, Raney BL: Evaluation of hydroxyl radical-scavenging property of garlic. Mol Cell Biochem 1996;154:55–63.
  26. Espirito Santo SM, van Vlijmen BJ, Buytenhek R, van Duyvenvoorde W, Havekes LM, Arnault I, Auger J, Princen HM: Well-characterized garlic-derived materials are not hypolipidemic in APOE*3-Leiden transgenic mice. J Nutr 2004;134:1500–1503.

    External Resources

  27. Espirito Santo SM, van Vlijmen BJ, van Duyvenvoorde W, Offerman EH, Havekes LM, Arnault I, Auger J, Princen HM: Absence of an atheroprotective effect of the garlic powder printanor in APOE*3-Leiden transgenic mice. Atherosclerosis 2004;177:291–297.
  28. Yeh YY, Liu L: Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies. J Nutr 2001;131:989S–993S.
  29. Lawson LD, Gardner CD: Composition, stability, and bioavailability of garlic products used in a clinical trail. J Agric Food Chem 2005;53:6254–6261.
  30. Hsu CC, Huang CN, Hung YC, Yin MC: Five cysteine-containing compounds have antioxidative activity in Balb/cA mice. J Nutr 2004;134:149–152.
  31. Rabinkov A, Miron T, Konstantinovski L, Wilchek M, Mirelman D, Weiner L: The mode of action of allicin: trapping of radicals and interaction with thiol containing proteins. Biochim Biophys Acta 1998;1379:233–244.
  32. Miron T, Bercovici T, Rabinkov A, Wilchek M, Mirelman D: [3H]Allicin: preparation and applications. Anal Biochem 2004;331:364–369.
  33. Hatch FT: Practical methods for plasma lipoprotein analysis. Adv Lipid Res 1968;6:1–68.
  34. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with Folin phenol reagent. J Biol Chem 1951;193:265–275.
  35. Gieseg SP, Esterbauer H: Low density lipoprotein is saturable by pro-oxidant copper. FEBS Lett 1994;343:188–194.
  36. Salacinski PR, McLean C, Sykes JE, Clement-Jones VV, Lowry PJ: Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl glycoluril (Iodogen). Anal Biochem 1981;117:136–146.
  37. Bellosta S, Mahley RW, Sanan DA, Murata J, Newland DL, Taylor JM, Pitas RE: Macrophage-specific expression of human apolipoprotein E reduces atherosclerosis in hypercholesterolemic apolipoprotein E-null mice. J Clin Invest 1995;96:2170–2179.
  38. Goldstein JL, Basu SK, Brown MS: Receptor-mediated endocytosis of low density lipoprotein in cultured cells. Methods Enzymol 1983;98:241–260.
  39. Ishibashi S, Herz J, Maeda N, Goldstein JL, Brown MS: The two-receptor model of lipoprotein clearance: tests of the hypothesis in ‘knockout’ mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins. Proc Natl Acad Sci USA 1994;91:4431–4435.
  40. Kruczala K, Schlick S: Interaction of ionomers and polyelectrolytes with divalent transition metal cations (Cu2+ and VO2+): a study by electron spin resonance (ESR) spectroscopy and viscosimetry. Polym Mat Sci Eng 1999;79:475–476.
  41. Millard CB, Shnyrov VL, Newstead S, Shin I, Roth E, Silman I, Weiner L: Stabilization of a metastable state of Torpedo californica acetylcholinesterase by chemical chaperones. Protein Sci 2003;12:2337–2347.
  42. Miron T, Rabinkov A, Mirelman D, Wilchek M, Weiner L: The mode of action of allicin: its ready permeability through phospholipid membranes may contribute to its biological activity. Biochim Biophys Acta 2000;1463:20–30.
  43. Eliash T, Weiner L, Ottolenghi M, Sheves M: Specific binding sites for cations in bacteriorhodopsin. Biophys J 2001;81:1155–1162.
  44. Aharoni A, Weiner L, Ottolenghi M, Sheves M: Bacteriorhodopsin experiences light-induced conformational alterations in nonisomerizable C(13) = C(14) pigments. A study with EPR. J Biol Chem 2000;275:21010–21016.
  45. Veniant MM, Withycombe S, Young SG: Lipoprotein size and atherosclerosis susceptibility in Apoe(–/–) and LDL-R(–/–) mice. Arterioscler Thromb Vasc Biol 2001;21:1567– 1570.
  46. Lawson DL, Wang ZJ: Allicin release under simulated gastrointestinal conditions from garlic powder tablets employed in clinical trials on serum cholesterol. Planta Med 2001;67:13–18.
  47. Lebedev VS, Volodina LA, Fedorov I: Analysis of the binding site of copper with intact and Escherichia coli bacteria modified by N-ethylmaleimide by ESR. Biofizika 1991;36:91–96.
  48. Hong SY, Yang JO, Lee EY, Lee ZW: Effects of N-acetyl-L-cystein and glutathion on antioxidant status of human serum and 3T3 fibroblasts. J Korean Med Sci 2003;18:649–654.
  49. Gruarin P, Sitia R, Alessio M: Formation of one or more intrachain disulphide bonds is required for the intracellular processing and transport of CD36. Biochem J 1997;328:635–642.
  50. Lawson LD, Wang ZJ: Allicin and allicin-derived garlic compounds increase breath acetone through allyl methyl sulfide: use in measuring allicin bioavailability. J Agric Food Chem 2005;53:1974–1983.
  51. Rosen RT, Hiserodt RD, Fukuda EK, Ruiz RJ, Zhou Z, Lech J, Rosen SL, Hartman TG: Determination of allicin, S-allylcysteine and volatile metabolites of garlic in breath, plasma or simulated gastric fluids. J Nutr 2001;131:968S–971S.

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