Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Antioxidative Effect of S-allylmercaptocysteine Derived from Aged Garlic on Oxidation of Human Low Density Lipoprotein

숙성 마늘 유래 S-allylmercaptocysteine의 human low density lipoprotein (LDL)에 대한 항산화 효과

  • Yang, Seung Taek (Department of Food Science and Biotechnology, Kyungsung University)
  • 양승택 (경성대학교 식품생명공학과)
  • Received : 2012.09.06
  • Accepted : 2012.12.10
  • Published : 2012.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Oxidation of low density lipoprotein (LDL) plays an important role in the development and progression of atherosclerotic disease. In this study, human LDL was isolated and oxidized using $CuSO_4$ in the presence or absence of S-allylmercaptocysteine. Oxidative modification of the LDL fraction was monitored by both the appearance of thiobarbituric acid substances (TBARS), an increase in electrophoretic mobility, and conjugated diene formation. The addition of S-allylmercaptocysteine reduced lipid peroxide formation, indicating it to be an effective antioxidant. The inhibition of LDL oxidation by $5{\sim}20{\mu}g/ml$ S-allylmercaptocysteine occurred in a dose-dependent manner, as assessed by the TBARS assay. S-allylmercaptocysteine at $20{\mu}g/ml$ almost completely inhibited the $Cu^{2+}$ induced increases in electrophoretic mobility of LDL and almost completely inhibited conjugated diene formation. A more potent antioxidative activity was observed for S-allylmercaptocysteine than for either Vitamin C or $d{\ell}-{\alpha}$-tocopherol. Thus, S-allylmercaptocysteine aid in preventing the development and progression of atherosclerotic disease.

Low density lipoprotein (LDL)의 산화는 동맥경화의 유발과 진행에 중요한 역할을 하는 것으로 알려져 있다. 본 연구는 숙성 마늘 유래 유황화합물인 S-allylmercaptocysteine의 항산화 효과를 실험하였다. S-allylmercaptocysteine의 항산화 효과는 $Cu^{2+}$ 유도 LDL에 대하여 thiobarturic acid substance (TBARS)와 전기영동 이동거리, 공액 이중결합으로 측정하였다. 사람 LDL을 $Cu^{2+}$ 유도로 산화시킬 때 S-allylmercaptocysteine은 용량 의존형으로 나타났으며, 농도가 $20{\mu}g/ml$ 일 때 거의 완전한 억제 효과를 나타내었다. S-allylmercaptocysteine에 대한 전기영동 이동거리로 $20{\mu}g/ml$ 일 때 가장 낮았으며 공액 2중결합 형성도 $20{\mu}g/ml$ 일 때 거의 억제되었다. 한편 S-allylmercaptocysteine을 항산화제인 $d{\ell}-{\alpha}$-tocopherol과 LDL에 대한 항산화력을 비교한 결과 같은 농도에서 S-allylmercaptocysteine이 약간 높았다. 따라서 S-allylmercaptocysteine이 동맥경화의 발병과 진행을 예방하는 역할을 할 것으로 생각된다.

Keywords

References

  1. Aviram, M. 1996. Interaction of oxidised low density lipoprotein with macrophages in atherosclerosis, and the antiatherogenicity of antioxidants. Eur. J. Clin. Chem. Clin. Biochem. 34, 599-607.
  2. Berliner, J. A., Navab, M., Fogelman, A. M., Frank, J. S., Demer, L. L., Edwards, P. A, Watson, A. D. and Lusis, A. J. 1995. Atherosclerosis: basic mechanisms. oxidation, inflammation, and genetics. Circulation 91, 2488-2496. https://doi.org/10.1161/01.CIR.91.9.2488
  3. Chiu, Y. T., Howard, E. W., Lee, D. T., Chua, C. W., Wang, X. and Wong, Y. C. 2008. Evidence of a novel docetaxel sensitizer, garlicderived S-allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer. Int. J. Cancer 122, 1941-1948. https://doi.org/10.1002/ijc.23355
  4. Esterbauer, H., Striegl, G., Puhl, H. and Rotheneder, M. 1989. Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Rad. Res. Commun. 6, 67-75. https://doi.org/10.3109/10715768909073429
  5. Evans, P. J., Smith, C., Mitchinson, M. J. and Halliwell, B. 1995. Meta lion release from mechanically disrupted human arterial wall. Implications for the development of atherosclerosis. Free Redic. Res. 25, 465-469.
  6. Fuster, V. 1994. Mechanisms leading to myocardial infarction: Insights from studies of vascular biology (Lewis, A. Conner Meorial Lecture). Circulation 90, 2126-2134. https://doi.org/10.1161/01.CIR.90.4.2126
  7. Gey, K. F. 1995. Ten-year retrospective on the antioxidant hypothesis of atherosclerosis: Threshold plasma levels of antioxidant micronutrients related to minimum cardiovascular risk. J. Nutr. Biochem. 6, 206-212. https://doi.org/10.1016/0955-2863(95)00032-U
  8. Greenspan, P. and Gutman, R. L. 1993. Detection by nile red of agarose fel electrophoresed native and modified low density lipoprotein. Electrophoresis 14, 65-68. https://doi.org/10.1002/elps.1150140111
  9. Havel, R. J., Eder, H. A. and Bragdon, J. H. 1995. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest. 34, 1345-1352.
  10. Howard, E. W., Ling, M. T., Chua, C. W., Cheung, H. W, Wang, X. and Wong, Y. C. 2007. Garlic-derived S-allylmer-captocysteine is a novel in vivo antimetastatic agent for and rogenindependent prostate cancer. Clin. Cancer Res. 13, 1847-1856. https://doi.org/10.1158/1078-0432.CCR-06-2074
  11. Ide, N. and Lau, B. H. 1997. Garlic compounds protect vascular endothelial cells from oxidized low density lip-oprotein-induced injury. J. Pharm. Pharmacol. 49, 908-911. https://doi.org/10.1111/j.2042-7158.1997.tb06134.x
  12. Ide, N., Nelson, A. B. and Lau, B. H. 1997. Aged garlic extract and its constituents inhibit $Cu^{2+}$-induced oxidative modification of low density lipoprotein. Planta Med. 63, 263-264. https://doi.org/10.1055/s-2006-957668
  13. Kuzuya, M. and Kuzuya, F. 1993. Probucol as an antioxidant and antiatherogenic drug. Free Rad. Biol. Med. 14, 67-77. https://doi.org/10.1016/0891-5849(93)90510-2
  14. Lawson, L. D. 1996. The composition and chemistry of garlic cloves and processed garlic, in garlic: The science and therapeutic application of allium sativum L. and related species. 2nd eds. In Koch, H. P. and Lawson, L. D. (eds.), pp. 37-107, Williams and Wilkins, Baltimore.
  15. Lawson, L. D. 1998. Garlic: review of its medicinal effects and indicated active compounds. In Phytomedicines of Europe, Chemistry and Biological Activity Edited by: Lawson, L. D., Bauer, R. Washington DC: ACS Symposium series 691. American Chemical Society pp. 176-209.
  16. Lowry, O. H., Rosebrough, N. J., Far, A. L. and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265-275.
  17. Maldonado, P. D., Barrera, D., Medina-Campos, O., Hernandez-Pando, R., Ibarra-Rubio, M. E. and Pedraza-Chaverri, J. 2003. Aged garlic extract attenuates gentamicin induced renal damage and oxidative stress in rats. Life Sci. 73, 2543-2556. https://doi.org/10.1016/S0024-3205(03)00609-X
  18. Munday, J. S., James, K. A., Fray, L. M., Kirkwood, S. W. and Thompson, K. G. 1999. Daily supplementation with aged extract, but not raw garlic, protect low density lipoprotein against in vitro oxidation. Atherosclerosis 143, 399-304. https://doi.org/10.1016/S0021-9150(98)00293-7
  19. Navab, M., Fogelman, A. M., Berliner, J. A., Territo, M. C., Demer, L. L., Frank, J. S., Watson, A. D., Edwards, P. A. and Lusis, A. J. 1995. Pathogenesis of atherosclerosis. Am. J. Cardiol. 76, 18C https://doi.org/10.1016/S0002-9149(99)80466-4
  20. Parthasarathy, S., Steinberg, S. D. and Witztum, J. L. 1992. The role of oxidized low density lipoproteins in the pathogenesis of atherosclerosis. Ann. Rev. Med. 43, 219-227. https://doi.org/10.1146/annurev.me.43.020192.001251
  21. Phelps, S. and Harris, W. S. 1993. Garlic supplementation and lipoprotein oxidation susceptibility. Lipids 28, 475-484. https://doi.org/10.1007/BF02535949
  22. Pietta, P. and Simonetti, P. 1996. Dietary flavonoids and interaction with endogenous antioxidants, Biochem. Mol. Biol. Inter. 44, 1069-1074.
  23. Pinto, J. Y., Lapsia, S., Shah, A., Santiago, H. and Kim, G. 2000. Antiprofierative effect of garlic derived and other allium related compounds, In Nutrition and Cancer Prevention : New insights into the role of phytochemicals : Advances in experimental medicine and biology. American institute for cancer research (eds). Vol. 492.
  24. Puhl, H., Waeg, G. and Esterbauer, H. 1994. Methods to determine oxidation of low density lipoprotein. Method Enzymol. 233, 425-432. https://doi.org/10.1016/S0076-6879(94)33049-2
  25. Smith, C., Michinson, M. J., Aruoma, I. O. and Halliwell, B. 1992. Stimulation of lipid peroxidation and hydroxyl radical generation by the contents of human atherosclerotic lesions. Biochem. J. 286, 901-905.
  26. Srivastava, K. C., Bordia, A. and Verma, S. K. 1995, Garlic (Allium sativum) for disease prevention, South African J. Sci. 91, 68-77.
  27. Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C. and Wiztum, J. L. 1987. Modifications of low density lipoprotein that increases its atherogenicity. N. Engl. J. Med. 320, 915-924.
  28. Steinbrecher, U. P., Zhang, H. and Lougheed, M. 1990. Role of oxidatively modified LDL in atherosclerosis. Free Rad. Biol. Med. 9, 155-168.
  29. Sumioks, I., Matsura, T. and Yamade, K. 2001. Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice. Eur. J. Pharmacol. 433, 177-185. https://doi.org/10.1016/S0014-2999(01)01503-5
  30. Sumioks, I., Matsura, T., Kasuga, S., Itakura, Y. and Yamada, L. 1998. Mechanisms of protection by S-allylmercaptocys-teine against acetaminophen-induced liver injury in mice. Jpn. J. Pharmacol. 78, 199-207. https://doi.org/10.1254/jjp.78.199
  31. Swain, J. and Gutteridge, T. M. 1995. Proxidant iron and copper, with ferroxidase and xanthine oxidase activities in human atherosclerotic material FEBS. Letters 368, 513-515. https://doi.org/10.1016/0014-5793(95)00726-P
  32. Xiao, D., Pinto, J. T., Soh, J. W., Deguchi, A., Gundersen, G. G., Palazzo, A. F., Yoon, J. T., Shirin, H. and Weinstein, I. B. 2003. Induction of apoptosis by the garlicderived compound S-allylmercaptocysteine (SAMC) is associated with microtuble depolymerization and cJun NH(2)-terminal kinase 1 activation. Cancer Res. 63, 25-37.
  33. Yaki, K. 1976. A simple fluorometric assay for lipoprotein in blood plasma. Biochem. Med. 15, 212-217. https://doi.org/10.1016/0006-2944(76)90049-1