Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Aged Garlic Extract and Its Components Inhibit Platelet Aggregation in Rat

흰쥐에서 흑마늘 추출물과 그 성분들에 의한 혈소판 응집억제 효과

  • Choi, You-Hee (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Jeong, Hyung-Min (College of Pharmacy and Research Institute of Drug Development, Chonnam National University) ;
  • Kyung, Kyu-Hang (Deptment of Food Science, Sejong University) ;
  • Ryu, Beung-Ho (DOUL Agircultural Farming Corp.) ;
  • Lee, Kwang-Youl (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
  • 최유희 (전남대학교 약학대학) ;
  • 정형민 (전남대학교 약학대학) ;
  • 경규항 (세종대학교 생명과학대학 식품공학부) ;
  • 류병호 (경남 남해군 고현면 도울농산영농조합) ;
  • 이광열 (전남대학교 약학대학)
  • Received : 2011.08.16
  • Accepted : 2011.09.28
  • Published : 2011.10.31
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Abstract

Many clinical trials have demonstrated the beneficial effects of garlic (Allium sativum) on general cardiovascular health. Aged garlic extract (AGE) is known to display diverse biological activities such as in antioxidant, anti-inflammatory and anticancer activities. However, few studies have been directed on the effect of AGE on cardiovascular function. In this study, we aimed to investigate the effect of AGE and its components on platelet activation, a key contributor in thrombotic diseases. In freshly isolated rat platelets, AGE and its components have shown inhibitory activities on thrombin-induced platelet aggregation. These in vitro results were further confirmed in an in vivo platelet aggregation measurement where tail vein injection of garlic oil and S-Allylmercapto-cysteine (SAMC) significantly reduced thrombin and ADP-induced platelet aggregation. Potential active components for antiplatelet effects of AGE were identified to be SAMC and diallyl sulphide through agonist-induced platelet aggregation assay. These results indicate that aged garlic extract can be a novel dietary supplement for the prevention of cardiovascular risks and the improvement of blood circulation.

많은 임상 실험을 통해 마늘(Allium sativum)이 심혈관 질환에 유효한 효과가 알려져 있다. 흑마늘(AGE)은 항산화, 항염증, 항암 효과 등 다양한 생물학적 효과가 보고되었다. 그러나, 흑마늘의 심혈관계 질환과의 상관관계에 대한 연구는 아직 미흡한 실정이다. 흑마늘과 그 유래 성분이 혈소판에 미치는 영향을 조사하였다. 백서의 혈액을 얻어, 흑마늘과 그 유래 성분의 thrombin에 의해 유도되는 혈소판 응집에 대한 억제 효과를 조사한 결과, 흑마늘과 diallyl sulphides는 농도의존적으로 혈소판 응집을 억제함을 관찰하였다. 또한 in vivo 실험에서도 마늘 오일과 S-Allylmercapto-cystein (SAMC)는 thrombin과 ADP에 의해 유도되는 혈소판 응집을 유의성 있게 억제하는 것을 관찰하였다. 흑마늘 유래 SAMC와 diallyl sulphides가 혈소판 응집 억제 효과를 나타내는 것을 확인할 수 있었다. 이러한 결과는 흑마늘이 심혈관계 질환의 예방을 위한 건강보조식품으로의 새로운 가능성을 제시한다.

Keywords

References

  1. Apitz-Castro, R., S. Cabrera, M. R. Cruz, E. Ledezma, and M. K. Jain. 1983. Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure. Thromb. Res. 32, 155-169. https://doi.org/10.1016/0049-3848(83)90027-0
  2. Baigent, C., L. Blackwell, R. Collins, J. Emberson, J. Godwin, R. Peto, J. Buring, C. Hennekens, P. Kearney, T. Meade, C. Patrono, M. C. Roncaglioni, and A. Zanchetti. 2009. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373, 1849-1860. https://doi.org/10.1016/S0140-6736(09)60503-1
  3. Banerjee, S. K. and S. K. Maulik. 2002. Effect of garlic on cardiovascular disorders: a review. Nutr. J. 1, 4. https://doi.org/10.1186/1475-2891-1-4
  4. Barrett, N. E., L. Holbrook, S. Jones, W. J. Kaiser, L. A. Moraes, R. Rana, T. Sage, R. G. Stanley, K. L. Tucker, B. Wright, and J. M. Gibbins. 2008. Future innovations in anti-platelet therapies. Br. J. Pharmacol. 154, 918-939. https://doi.org/10.1038/bjp.2008.151
  5. Block, E. 1996. Recent results in the organosulfur and organoselenium chemistry of genus Allium and Brassica plants. Relevance for cancer prevention. Adv. Exp. Med. Biol. 401, 155-169. https://doi.org/10.1007/978-1-4613-0399-2_13
  6. Bordia, A. 1978. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 30, 355-360. https://doi.org/10.1016/0021-9150(78)90129-6
  7. Bordia, A., S. K. Verma, and K. C. Srivastava. 1996. Effect of garlic on platelet aggregation in humans: a study in healthy subjects and patients with coronary artery disease. Prostaglandins Leukot. Essent. Fatty Acids 55, 201-205. https://doi.org/10.1016/S0952-3278(96)90099-X
  8. Bordia, A., S. K. Verma, and K. C. Srivastava. 1998. Effect of garlic (Allium sativum) on blood lipids, blood sugar, fibrinogen and fibrinolytic activity in patients with coronary artery disease. Prostaglandins Leukot. Essent. Fatty Acids 58, 257-263. https://doi.org/10.1016/S0952-3278(98)90034-5
  9. Briggs, W. H., J. D. Folts, H. E. Osman, and I. L. Goldman. 2001. Administration of raw onion inhibits platelet-mediated thrombosis in dogs. J. Nutr. 131, 2619-2622.
  10. Chang, H. S, O. Yamato, Y. Sakai, M. Yamasaki, and Y. Maede. 2004. Acceleration of superoxide generation in polymorphonuclear leukocytes and inhibition of platelet aggregation by alk(en)yl thiosulfates derived from onion and garlic in dogs and humans. Prostaglandins Leukot. Essent. Fatty Acids 70, 77-83. https://doi.org/10.1016/j.plefa.2003.08.006
  11. Dillon, S. A., G. M. Lowe, D. Billington, and K. Rahman. 2002. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. J. Nutr. 132, 168-171.
  12. Dillon, S. A., R. S. Burmi, G. M. Lowe, D. Billington, and K. Rahman. 2003. Antioxidant properties of aged garlic extract: an in vitro study incorporating human low density lipoprotein. Life Sci. 72, 1583-1594. https://doi.org/10.1016/S0024-3205(02)02475-X
  13. Dwivedi, C., A. Abu-Ghazaleh, and J. Guenther. 1996. Effects of diallyl sulfide and diallyl disulfide on cisplatin-induced changes in glutathione and glutathione-S-transferase activity. Anticancer Drugs 7, 792-794. https://doi.org/10.1097/00001813-199609000-00012
  14. Gachet, C. 2001. ADP receptors of platelets and their inhibition. Thromb. Haemost. 86, 222-232.
  15. Gachet, C. 2001. Identification, characterization, and inhibition of the platelet ADP receptors. Int. J. Hematol. 74, 375-381. https://doi.org/10.1007/BF02982079
  16. Gadkari, J. V. and V. D. Joshi. 1991. Effect of ingestion of raw garlic on serum cholesterol level, clotting time and fibrinolytic activity in normal subjects. J. Postgrad. Med. 37, 128-131.
  17. Haber, D., M. H. Siess, M. C. Canivenc-Lavier, A. M. Le Bon, and M. Suschetet. 1995. Differential effects of dietary diallyl sulfide and diallyl disulfide on rat intestinal and hepatic drug-metabolizing enzymes. J. Toxicol. Environ. Health 44, 423-434. https://doi.org/10.1080/15287399509531971
  18. Jackson, S. P. and S. M. Schoenwaelder. 2003. Antiplatelet therapy: in search of the 'magic bullet'. Nat. Rev. Drug Discov. 2, 775-789. https://doi.org/10.1038/nrd1198
  19. Lawson, L. D., D. K. Ransom, and B. G. Hughes. 1992. Inhibition of whole blood platelet-aggregation by compounds in garlic clove extracts and commercial garlic products. Thromb. Res. 65, 141-156. https://doi.org/10.1016/0049-3848(92)90234-2
  20. Legnani, C., M. Frascaro, G. Guazzaloca, S. Ludovici, G. Cesarano, and S. Coccheri. 1993. Effects of a dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. Arzneimittelforschung 43, 119-122.
  21. Munday, J. S., K. A. James, L. M. Fray, S. W. Kirkwood, and K. G. Thompson. 1999. Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 143, 399-404. https://doi.org/10.1016/S0021-9150(98)00293-7
  22. Puri, R. N. 1998. Phospholipase A2: its role in ADP- and thrombin-induced platelet activation mechanisms. Int. J. Biochem. Cell Biol. 30, 1107-1122. https://doi.org/10.1016/S1357-2725(98)00080-6
  23. Qi, R., F. Liao, K. Inoue, Y. Yatomi, K. Sato, and Y. Ozaki. 2000. Inhibition by diallyl trisulfide, a garlic component, of intracellular Ca(2+) mobilization without affecting inositol-1,4, 5-trisphosphate (IP(3)) formation in activated platelets. Biochem. Pharmacol. 60, 1475-1483. https://doi.org/10.1016/S0006-2952(00)00467-6
  24. Rahman, K. and D. Billington. 2000. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J. Nutr. 130, 2662-2665.
  25. Rahman, K. 2001. Historical perspective on garlic and cardiovascular disease. J. Nutr. 131, 977S-979S.
  26. Rahman, K. 2003. Garlic and aging: new insights into an old remedy. Ageing Res. Rev. 2, 39-56. https://doi.org/10.1016/S1568-1637(02)00049-1
  27. Rahman, K. and G. M. Lowe. 2006. Garlic and cardiovascular disease: a critical review. J. Nutr. 136, 736S-740S.
  28. Rahman, K. 2007. Effects of garlic on platelet biochemistry and physiology. Mol. Nutr. Food Res. 51, 1335-1344. https://doi.org/10.1002/mnfr.200700058
  29. Steiner, M., A. H. Khan, D. Holbert, and R. I. Lin. 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.
  30. Steiner, M. and R. S. Lin. 1998. Changes in platelet function and susceptibility of lipoproteins to oxidation associated with administration of aged garlic extract. J. Cardiovasc. Pharmacol. 31, 904-908. https://doi.org/10.1097/00005344-199806000-00014
  31. Steiner, M. and W. Li. 2001. Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. J. Nutr. 131, 980S-984S.
  32. Srivastava, K. C. 1984. Aqueous extracts of onion, garlic and ginger inhibit platelet aggregation and alter arachidonic acid metabolism. Biomed. Biochim. Acta. 43, S335-346.
  33. Superko, H. R. and R. M. Krauss. 2000. Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a). J. Am. Coll. Cardiol. 35, 321-326. https://doi.org/10.1016/S0735-1097(99)90541-7
  34. Tsao, S. M. and M. C. Yin. 2001. In-vitro antimicrobial activity of four diallyl sulphides occurring naturally in garlic and Chinese leek oils. J. Med. Microbiol. 50, 646-649.
  35. Vanderhoek, J. Y., A. N. Makheja, and J. M. Bailey. 1980. Inhibition of fatty acid oxygenases by onion and garlic oils. Evidence for the mechanism by which these oils inhibit platelet aggregation. Biochem. Pharmacol. 29,3169-3173. https://doi.org/10.1016/0006-2952(80)90581-X
  36. Wang, H. X. and T. B. Ng. 1999. Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities. Life Sci. 65, 2663-2677. https://doi.org/10.1016/S0024-3205(99)00253-2
  37. Wu, C. C., L. Y. Sheen, H. W. Chen, S. J. Tsai, and C. K. Lii. 2001. Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells. Food Chem. Toxicol. 39, 563-569. https://doi.org/10.1016/S0278-6915(00)00171-X
  38. Yamada, K., A. Naemura, N. Sawashita, Y. Noguchi, and J. Yamamoto. 2004. An onion variety has natural antithrombotic effect as assessed by thrombosis/thrombolysis models in rodents. Thromb. Res. 114, 213-220. https://doi.org/10.1016/j.thromres.2004.06.007

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