α-Asarone이 항산화 활성 및 기질금속단백질 분해효소 활성 조절에 미치는 영향

DOI QR코드

DOI QR Code

박혜정;김문무
Park, Hye-Jung;Kim, Moon-Moo

  • 투고 : 2015.06.24
  • 심사 : 2015.08.13
  • 발행 : 2015.09.30

초록

α-Asarone은 동양의 전통적인 약재로 잘 알려진 석창포(Acorus gramineus)의 주된 성분이다. 석창포는 항위궤양, 항알러지, 히스타민 방출 억제 그리고 항산화 효과와 같이 다양한 효과를 나타내는 것으로 잘 알려져 있다. 그러나 석창포 역할에 대한 기전연구는 아직 부족한 실정이다. 본 연구에서는, HT1080 세포주에서 α-asarone의 항산화 효과뿐만 아니라 matrix metalloproteinase에 대한 효과를 조사하였다. 가장 먼저 α-asarone의 세포 생존에 대한 효과를 조사하기 위해 MTT assay를 이용하여 16 μM이하에서 세포독성이 없음을 나타내었다. α-asarone이 환원력과 fenton reaction에 의해 유도된 DNA 산화로부터 보호효과를 나타내는 것을 확인하였다. 더욱이, α- asarone은 collagenase 활성을 증가시키고 phorbol 12-myristate 13-acetate (PMA)로 자극된 MMP-2 및 MMP-9의 활성을 증가시켰다. 한편 phenazine methosulfate (PMS) 로 자극된 경우 MMP-9의 활성은 α-asarone의 존재하에서 증가되었으나 MMP-2 활성에는 변화가 없었다. 그러므로 우리의 연구결과는 α-asarone이 산화적 스트레스 및 MMPs와 관련된 병리학적 질환의 예방 및 치료제로 개발이 기대된다고 제안한다.

키워드

α-Asarone;Acorus gramineus;antioxidant;collagenase;matrix metalloproteinase

참고문헌

  1. Salo, T., Mäkelä, M., Kylmäniemi, M., Autio-Harmainen, H. and Larjava, H. 1994. Expression of matrix metalloproteinase-2 and-9 during early human wound healing. Lab. Invest. 70, 176-182.
  2. Sambrook, J., Fritsch, E. F. and Maniatis, T. 1989. Molecular cloning: a laboratory manual: Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1977.
  3. Shin, J. W., Cheong, Y. J., Koo, Y. M., Kim, S., Noh, C. K., Son, Y. H., Kang, C. and Sohn, N. W. 2014. Alpha-asarone Ameliorates memory deficit in lipopolysaccharide-treated mice via suppression of pro-inflammatory cytokines and microglial activation. Biomol. Ther. 22, 17-26. https://doi.org/10.4062/biomolther.2013.102
  4. Simon, H. U., Haj-Yehia, A. and Levi-Schaffer, F. 2000. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5, 415-418. https://doi.org/10.1023/A:1009616228304
  5. Taniyama, Y. and Griendling, K. K. 2003. Reactive oxygen species in the vasculature molecular and cellular mechanisms. Hypertension 42, 1075-1081. https://doi.org/10.1161/01.HYP.0000100443.09293.4F
  6. Vihinen, P. and Kähäri, V. M. 2002. Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int. J. Cancer 99, 157-166. https://doi.org/10.1002/ijc.10329
  7. Limón, I. D., Mendieta, L., Díaz, A., Chamorro, G., Espinosa, B., Zenteno, E. and Guevara, J. 2009. Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-β (25-35). Neurosci. Lett. 453, 98-103. https://doi.org/10.1016/j.neulet.2009.02.011
  8. Manikandan, S. and Devi, R. S. 2005. Antioxidant property of alphaasarone against noise-stress-induced changes in different regions of rat brain. Pharmacol. Res. 52, 467-474. https://doi.org/10.1016/j.phrs.2005.07.007
  9. Martin, P. 1997. Wound healing--aiming for perfect skin regeneration. Science 276, 75-81. https://doi.org/10.1126/science.276.5309.75
  10. Mittler, R. 2002. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci. 7, 405-410. https://doi.org/10.1016/S1360-1385(02)02312-9
  11. Neufeld, G., Cohen, T., Gengrinovitch, S. and Poltorak, Z. 1999. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13, 9-22.
  12. Oyaizu, M. 1986. Studies on product of browning reaction prepared from glucose amine. Jpn. J. Nutr. 44, 307-315. https://doi.org/10.5264/eiyogakuzashi.44.307
  13. Pages, N., Maurois, P., Delplanque, B., Bac, P., Stables, J. P., Tamariz, J., Chamorro, G. and Vamecq, J. 2010. Activities of α-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties. Neurosci. Res. 68, 337-344. https://doi.org/10.1016/j.neures.2010.08.011
  14. Park, H. J., Lee, S. J. and Kim, M. M. 2015. Effect of α-asarone on angiogenesis and matrix metalloproteinase. Environ. Toxico.l Pharmacol. 39, 1107-1114. https://doi.org/10.1016/j.etap.2015.04.005
  15. Rodríguez-Páez, L., Juárez-Sanchez, M., Antúnez-Solís, J., Baeza, I. and Wong, C. 2003. α-Asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats. Phytomedicine 10, 397-404. https://doi.org/10.1078/0944-7113-00274
  16. Cho, J., Kim, Y. H., Kong, J. Y., Yang, C. H. and Park, C. G. 2002. Protection of cultured rat cortical neurons from excitotoxicity by asarone, a major essential oil component in the rhizomes of Acorus gramineus. Life Sci. 71, 591-599. https://doi.org/10.1016/S0024-3205(02)01729-0
  17. Coussens, L. M., Fingleton, B. and Matrisian, L. M. 2002. Matrix metalloproteinase inhibitors and cancer-trials and tribulations. Science 295, 2387-2392. https://doi.org/10.1126/science.1067100
  18. Hansen, M. B., Nielsen, S. E. and Berg, K. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119, 203-210. https://doi.org/10.1016/0022-1759(89)90397-9
  19. 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 Medica 60, 417-420. https://doi.org/10.1055/s-2006-959522
  20. Jain, N., Jain, R., Jain, A., Jain, D. K. and Chandel, H. S. 2010. Evaluation of wound-healing activity of Acorus calamus Linn. Nat. Prod. Res. 24, 534-541. https://doi.org/10.1080/14786410802531782
  21. Kim, M. M., Ta, Q. V., Mendis, E., Rajapakse, N., Jung, W. K., Byun, H. G., Jeon, Y. J. and Kim, S. K. 2006. Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity. Life Sci. 79, 1436-1443. https://doi.org/10.1016/j.lfs.2006.04.022
  22. Lee, K. W. and Lee, H. J. 2006. Biphasic effects of dietary antioxidants on oxidative stress-mediated carcinogenesis. Mechsm Age. Dev. 127, 424-431. https://doi.org/10.1016/j.mad.2006.01.021
  23. Lee, S. J., Seo, K. W., Yun, M. R., Bae, S. S., Lee, W. S., Hong, K. W. and Kim, C. D. 2008. 4-Hydroxynonenal enhances MMP-2 production in vascular smooth muscle cells via mitochondrial ROS-mediated activation of the Akt/NF kappaBsignaling pathways. Free Radic. Biol. Med. 45, 1487-1492. https://doi.org/10.1016/j.freeradbiomed.2008.08.022
  24. Apel, K. and Hirt, H. 2004. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu. Rev. Plant Biol. 55, 373-399. https://doi.org/10.1146/annurev.arplant.55.031903.141701
  25. Bergers, G., Brekken, R., McMahon, G., Vu, T. H., Itoh, T., Tamaki, K., Tanzawa, K., Thorpe, P., Itohara, S., Werb, Z. and Hanahan, D. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2, 737-744. https://doi.org/10.1038/35036374