Journal of Life Science (생명과학회지)

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

DOI QR Code

In vitro Inhibitory Effect of Aged Black Garlic Extract with Antioxidant Activity on MMP-2 and MMP-9 Related to Metastasis

In vitro에서 항산화 효능이 있는 흑마늘 추출물의 MMP-2 및 MMP-9에 대한 활성 억제효과

  • Lee, Soo-Jin (Department of Chemistry, Dong-Eui University) ;
  • Nam, Hyang (Department of Chemistry, Dong-Eui University) ;
  • Kim, Moon-Moo (Department of Chemistry, Dong-Eui University) ;
  • Jang, Ho-Jung (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Park, Jung-Ae (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Kim, Byung-Woo (Department of Life Science and Biotechnology, Dong-Eui University) ;
  • Chung, Kyung-Tae (Blue-Bio Industry RIC, Dong-Eui University)
  • 이수진 (동의대학교 화학과) ;
  • 남향 (동의대학교 화학과) ;
  • 김문무 (동의대학교 화학과) ;
  • 장호정 (동의대학교 생명응용과학과) ;
  • 박정애 (동의대학교 생명응용과학과) ;
  • 김병우 (동의대학교 생명응용과학과) ;
  • 정경태 (동의대학교 블루바이오 소재 개발 센터)
  • Received : 2010.04.06
  • Accepted : 2010.04.16
  • Published : 2010.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

The oxidative damage of lipids, protein, and DNA is known to be involved in not only chronic inflammations such as arthritis, hepatitis, nephritis, gastritis, colitis, and periodontitis but also metastasis. It has given impetus to searching for natural compounds without toxicity, which prevent the development of these diseases. The direct scavenging effects of aged black garlic extract (ABGE) were evaluated in vitro on DPPH radical, hydroxyl radical, hydrogen peroxide, and genomic DNA damage related to oxidative stress. Furthermore, its antioxidant effect on lipid peroxidation was investigated in human fibrosarcoma cells (HT1080), which were exposed to the hydroxyl radical generated by the Fenton reaction. It was observed that ABGE exhibited a greater inhibitory effect on hydrogen peroxide than other reactive oxygen species, and also blocked DNA oxidation and lipid peroxidation induced by the hydroxyl radical. The oxidative stress in live cells was also inhibited in the presence of ABGE. In addition, its inhibitory effects on the activity and expression of MMP-2 and -9 related to metastasis were determined using gelatin zymography and western blot. The data showed that it inhibited MMP-2 and -9 in PMA-stimulated HT1080 cells. Therefore, these results suggest that ABGE show potential as an excellent agent for prevention of metastasis related to oxidative stress.

지질, 단백질 및 DNA의 산화적 손상이 관절염, 간염, 위염, 대장염 및 치주 질환과 같은 만성 염증뿐만 아니라 암 전이에 관련되어 있다고 알려져 있다. 이러한 질환의 발생을 예방하기 위하여 독성이 없는 천연 화합물을 개발하는 것이 최근의 주요 연구 관심 대상이다. 산화적 스트레스와 관련 있는 DPPH radical, hydrogen peroxide, hydroxyl radical 및 과산화수소와 같은 활성산소에 대한 흑마늘(ABGE)의 소거능력이 연구되었다. 뿐만 아니라 TBARS assay를 이용하여 본 연구에서 사용된 산화방법으로 Fenton반응에 의하여 hydroxyl radical에 노출된 세포에서 ABGE의 항산화 효과도 조사되었다. ABGE는 활성산소종 중에서 특히 과산화수소에 대한 항산화 효능이 우수하였고 hydroxyl radical에 노출된 genomic DNA의 산화에 대한 보호 효과도 관찰되었다. 살아있는 세포에 대한 산화적 스트레스도 ABGE의 존재 하에서 억제되었다. 뿐만 아니라, 암전이와 관련 있는 MMP-2 및 MMP-9의 활성과 발현에 대한 ABGE의 효과를 gelatin zymography 및 western blot을 이용하여 조사하였다. ABGE는 PMA로 자극한 사람 섬유아육종세포로부터 분비된 MMP-2 및 MMP-9의 활성과 발현을 동시에 억제 하였으므로 암을 억제 할 수 있는 하나의 생리활성물질로 개발 될 수 있으리라 판단된다.

Keywords

References

  1. Agarwal, K. 1996. Therapeutic actions of garlic constituents. Medicinal Research Reviews 16, 111-124. https://doi.org/10.1002/(SICI)1098-1128(199601)16:1<111::AID-MED4>3.0.CO;2-5
  2. Ara, T. and Y. DeClerck. 2006. Mechanisms of invasion and metastasis in human neuroblastoma. Cancer and Metastasis Reviews 25, 645-657. https://doi.org/10.1007/s10555-006-9028-9
  3. Aronne, L., D. Nelinson, and J. Lillo. 2009. Obesity as a disease state: A new paradigm for diagnosis and treatment. Clinical Cornerstone 9, 9-29.
  4. Brand-Williams, W., M. Cuvelier, and C. Berset. 1995. Use of a free radical method to evaluate antioxidant activity. LWT-Food Science and Technology 28, 25-30. https://doi.org/10.1016/S0023-6438(95)80008-5
  5. Chen, P., Y. Hsieh, H. Chiou, and S. Chu. 2005. Silibinin inhibits cell invasion through inactivation of both PI3K-Akt and MAPK signaling pathways. Chemico-biological interactions 156, 141-150. https://doi.org/10.1016/j.cbi.2005.08.005
  6. Cheng, A., C. H. Hsu, J. K. Lin, M. M. Hsu, Y. F. Ho, T. S. Shen, J. Y. Ko, J. T. Lin, B. R. Lin, W. Ming-Shiang, H. S. Yu, S. H. Jee, G. S. Chen, T. M. Chen, C. A. Chen, M. K. Lai, Y. S. Pu, M. H. Pan, Y. J. Wang, C. C. Tsai, and C. Y. Hsieh. 2001. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Research 21, 2895-2900.
  7. Cho, S., E. Bae, C. Lee, C. You, and J. Lee. 2003. A case of irritant contact dermatitis due to garlic. Korean Journal of Dermatology 41, 385-387.
  8. Choi, C., S. Kim, S. Hwang, B. Choi, H. Ahn, M.Lee, S. Park, and S. Kim. 2002. Antioxidant activity and free radical scavenging capacity between Korean medicinal plants and flavonoids by assay-guided comparison. Plant science (Limerick) 163, 1161-1168. https://doi.org/10.1016/S0168-9452(02)00332-1
  9. Chung, S., T. Osawa, and S. Kawakishi. 1997. Hydroxyl radical-scavenging effects of spices and scavengers from brown mustard (Brassica nigra). Bioscience, biotechnology, and biochemistry 61, 118-123. https://doi.org/10.1271/bbb.61.118
  10. Hansen, M., S. Nielsen, and K. Berg. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. Journal of Immunol Methods 119, 203-210. https://doi.org/10.1016/0022-1759(89)90397-9
  11. Hasani-Ranjbar, S., B. Larijani, and M. Abdollahi.2009. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflammation and Allergy 8, 2-10. https://doi.org/10.2174/187152809787582561
  12. Imai, J., N. Ide, S. Nagae, T. Moriguchi, H. Matsuura, and Y. Itakura. 1994. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Medica 60, 417. https://doi.org/10.1055/s-2006-959522
  13. Jang, M. L. Cai, G. O. Udeani, K. V. Slowing, C. F. Thomas, C. W. Beecher, H. H. Fong, N. R. Farnsworth, A. D. Kinghorn, R. G. Mehta, R. C. Moon, J. M. Pezzuto. 1997. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218-220. https://doi.org/10.1126/science.275.5297.218
  14. Lightfoot, T, C. F. Skibola, A. G. Smith, M. S. Forrest, P. J. Adamson, G. J. Morgan, P. M. Bracci, E. Roman, M. T. Smith, and E. A. Holly. 2006. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Haematologica 91, 1222-1227.
  15. Looi, M., A. Z. Mohd Dali, S. A. Md Ali, W. Z. Wan Ngah, and Y. A. Mohd Yusof. 2008. Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix. European Journal of Cancer Prevention 17, 555-560. https://doi.org/10.1097/CEJ.0b013e328305a10b
  16. Medi - ari , M., V. Rastija, M. Boji, and Male. 2009. From functional food to medicinal product: Systematic approach in analysis of polyphenolics from propolis and wine. Nutrition Journal 8, 33. https://doi.org/10.1186/1475-2891-8-33
  17. Milne, L, P. Nicotera, S. Orrenius, and M., B. 1993. Effects of glutathione andchelating agents on copper-mediated DNA oxidation: pro-oxidant and antioxidant properties of glutathione. .Archives of Biochemistry and Biophysics 304, 102-109. https://doi.org/10.1006/abbi.1993.1327
  18. Ohnishi, N. and T. Yokoyama. 2004. Interactions between medicines and functional foods or dietary supplements. The Keio Journal of Medicine 53, 137-150. https://doi.org/10.2302/kjm.53.137
  19. Oyaizu, M. 1986. Studies on products of browning reaction: antioxidative activities of products of browning reaction prepared from glucosamine. Japonesse.Journal of Nutrition 44, 307-305. https://doi.org/10.5264/eiyogakuzashi.44.307
  20. Queiroz, Y., E. Ishimoto, D. Bastos, G. Sampaio, and E. Torres. 2009. Garlic (Allium sativum L.) and ready-to-eat garlic products: In vitro antioxidant activity. Source. Food Chemistry 115, 371-374. https://doi.org/10.1016/j.foodchem.2008.11.105
  21. Raju, J. and R. Mehta. 2009. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin. Nutrition and Cancer 61, 27-35. https://doi.org/10.1080/01635580802357352
  22. Reddy, A. and B. Lokesh. 1994. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Molecular and Cellular Biochemistry 137, 1-8. https://doi.org/10.1007/BF00926033
  23. Rona, C. and E. Berardesca. 2008. Aging skin and food supplements: the myth and the truth. Clinics in Dermatology 26, 641-647. https://doi.org/10.1016/j.clindermatol.2007.09.002
  24. Shukla, Y. and N. Kalra. 2007. Cancer chemoprevention with garlic and its constituents. Cancer Letters 247, 167-181. https://doi.org/10.1016/j.canlet.2006.05.009
  25. Sirtori, C., C. Galli, J. Anderson, E. Sirtori, and A. Arnoldi. 2009. Functional foods for dyslipidaemia and cardiovascular risk prevention. Nutrition Research Reviews 22, 244-261. https://doi.org/10.1017/S0954422409990187
  26. Vasanthi, H., S. Mukherjee, and D. Das.2009. Potential Health Benefits of Broccoli-A Chemico-Biological Overview. Mini Reviews in Medicinal Chemistry 9, 749-759. https://doi.org/10.2174/138955709788452685
  27. Wilson, E. and B. Demmig-Adams. 2007. Antioxidant, anti-inflammatory, and antimicrobial properties of garlic and onions. Nutrition & Food Science 37, 178-183. https://doi.org/10.1108/00346650710749071
  28. Yoon, G. 2006. Effect of garlic supplement and exercise on plasma lipid and antioxidant enzyme system in rats. The Korean Journal of Nutrition 39, 3-10.
  29. Yu, T., C. Wu, and S. Chen. 1989. Effects of pH adjustment and heat treatment on the stability and the formation of volatile compounds of garlic. Journal of Agricultural and Food Chemistry 37, 730-734. https://doi.org/10.1021/jf00087a033

Cited by

  1. Effect of Polygala radix Hot Water Extract on Biological Activity in PC12 Cells vol.23, pp.8, 2013, https://doi.org/10.5352/JLS.2013.23.8.1041
  2. The Physicochemical Characteristics and Antioxidant Properties of Commercial Nurungji Products in Korea vol.32, pp.5, 2016, https://doi.org/10.9724/kfcs.2016.32.5.575
  3. Recovery Effect of Garlic Extract and Vitamin B group Enhanced Diet on Swimming Fatigue vol.21, pp.6, 2011, https://doi.org/10.5352/JLS.2011.21.6.875
  4. Improvement of Antioxidative Activity by Enzyme Treatment and Lactic Acid Bacteria Cultivation in Black Garlic vol.40, pp.5, 2011, https://doi.org/10.3746/jkfn.2011.40.5.660
  5. UnripeRubus coreanusMiquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression vol.78, pp.8, 2014, https://doi.org/10.1080/09168451.2014.921550