생명과학회지 (Journal of Life Science)

  • 제27권7호
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  • Pages.783-789
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  • 2017
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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Malus melliana 에탄올 추출물의 항산화 및 항염증 활성

The Anti-oxidative and Anti-inflammatory Activities of Malus melliana Ethanol Extract

  • 이수현 (동의대학교 블루바이오소재개발 및 실용화 지원센터) ;
  • 진경숙 (동의대학교 블루바이오소재개발 및 실용화 지원센터) ;
  • 김병우 (동의대학교 블루바이오소재개발 및 실용화 지원센터) ;
  • 권현주 (동의대학교 블루바이오소재개발 및 실용화 지원센터)
  • Lee, Su Hyeon (Blue-Bio Industry Regional Innovation Center, Dong-Eui University) ;
  • Jin, Kyong-Suk (Blue-Bio Industry Regional Innovation Center, Dong-Eui University) ;
  • Kim, Byung Woo (Blue-Bio Industry Regional Innovation Center, Dong-Eui University) ;
  • Kwon, Hyun Ju (Blue-Bio Industry Regional Innovation Center, Dong-Eui University)
  • 투고 : 2017.01.05
  • 심사 : 2017.04.27
  • 발행 : 2017.07.30
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초록

Malus melliana (Hand.-Mazz.) Rehder (M. melliana)는 장미과에 속하는 중국 자생 식물 중 하나로 현재까지 보고된 생리활성은 전무하다. 본 연구에서는 M. melliana 에탄올 추출물(MMEE)의 항산화 및 항염증 생리활성을 DPPH 라디칼 소거능, ROS 소거능, NO 생성 저해능 및 Western blot hybridization을 통한 연관 단백질 발현분석을 통해 평가하였다. MMEE의 항산화능을 DPPH 라디칼 소거능을 통해 분석한 결과 양성 대조군으로 사용한 대표적인 항산화제인 아스코르빈산과 유사한 정도의 높은 소거활성을 보여 MMEE가 매우 강한 항산화능을 보유함을 확인하였다. 또한 RAW 264.7 세포주에서 $H_2O_2$에 의해 유도된 ROS에 대한 MMEE의 소거능을 분석한 결과, 농도의존적인 강한 ROS 소거능을 보였다. 뿐만 아니라 대표적인 항산화 효소인 HO-1 및 그 전사 인자인 Nrf2의 단백질 발현에 미치는 영향을 분석한 결과 MMEE에 의해 HO-1 및 Nrf2의 발현이 증가됨을 보였다. 한편 MMEE가 LPS에 의해 유도된 NO 생성에 미치는 영향을 분석한 결과 농도의존적인 NO 생성 저해능을 보였으며 이는 NO 생성 단백질인 iNOS의 발현 저해에서 기인함을 확인하였다. 이러한 결과를 통해 MMEE의 높은 항산화능과 항염증 활성을 확인하였으며 향후 잠재적인 기능성 소재로서 유용하게 활용될 수 있을 것으로 판단된다. 추후 계속적인 연구를 통해 활성 물질의 규명이 필요할 것으로 판단된다.

Malus melliana (Hand.-Mazz.) Rehder (M. melliana) is a Chinese plant that belongs to the Rosaceae family. There have been no previous reports regarding its bioactivity. In this study, the anti-oxidative and anti-inflammatory activities of M. melliana ethanol extract (MMEE) were evaluated using a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity assay, reactive oxygen species (ROS) scavenging activity assay, nitric oxide (NO) inhibitory activity assay, and the analysis of related protein expressions through Western blot hybridization. MMEE showed potent scavenging activity against DPPH, similar to ascorbic acid, a well-known anti-oxidative agent, which was used as a positive control. MMEE also inhibited hydrogen peroxide-induced ROS in RAW 264.7 cells. Moreover, MMEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1, and its upstream transcription factor, nuclear factor E2-related factor-2, in a dose-dependent manner. On the other hand, MMEE was associated with a reduction in NO production, which was induced by the lipopolysaccharide treatment of RAW 264.7 cells. The expression of inducible nitric oxide synthase, which is the upstream regulator of NO production, was also inhibited. Taken together, these results suggest that MMEE has anti-oxidative and anti-inflammatory properties, thus appearing to be a potential anti-oxidant and anti-inflammatory agent. The further identification of active compounds that confer the biological activities of MMEE may be necessary.

키워드

참고문헌

  1. Ames, B. N., Shingenaga, M. K. and Hagen, T. M. 1993. Oxidants, antioxidants, and the degenerative diseases of aging. Proc. Natl. Acad. Sci. USA 90, 7915-7922. https://doi.org/10.1073/pnas.90.17.7915
  2. Azuma, K., Nakayama, M., Koshica, M., Lppoushi, K., Yamaguchi, Y., Kohata, K., Yamaguchi, Y., Ito, H. and Higashio, H. 1999. Phenolic antioxidants from the leaves of Corchorus olitorius L. J. Agric. Food Chem. 47, 3963-3966. https://doi.org/10.1021/jf990347p
  3. Balogun, E., Hoque, M., Gong, P., Killeen, E., Green, C. J., Foresti, R., Alam, J. and Motterlini, R. 2003. Curcumin activates the heme oxygenase-1 gene via regulation of Nrf2 and the antioxidant responsive element. Biochem. J. 371, 887-895. https://doi.org/10.1042/bj20021619
  4. Beckman, K. B. and Ames, B. N. 1979. The free radical theory of aging matures. Physiol. Rev. 59, 527-605. https://doi.org/10.1152/physrev.1979.59.3.527
  5. Gonzalez-Burgos, E. and Gomez-Serranillos, M. P. 2012. Terpene compounds in nature: a review of their potential antioxidant activity. Curr. Med. Chem. 19, 5319-5341. https://doi.org/10.2174/092986712803833335
  6. Guertler, A., Kraemer, A., Roessler, U., Hornhardt, S., Kulka, U., Moertl, S., Friedl, A. A., Illig, T., Wichmann, E. and Gomolka, M. 2011. The WST survival assay: an easy and reliable method to screen radiation-sensitive individuals. Radiat. Prot. Dosimetry 143, 487-490. https://doi.org/10.1093/rpd/ncq515
  7. Hofseth, L. J. and Ying, L. 2006. Identifying and defusing weapons of mass inflammation in carcinogenesis. Biochim. Biophys. Acta 1765, 74-84.
  8. Hu, F. and Lu, R. 2004. Studies on scavenging activities to DPPH free radical of extracts from fresh leaves of some woody plants of Rosaceae. Chinese Bull. Botany 21, 74-78.
  9. Hwang, S. M., Chen, C. H., Chen, S. S. and Chen, J. C. 2000. Chitinous materials inhibit nitric oxide production by activated RAW 264.7 macrophages. Biochem. Biophys. Res. Commun. 271, 229-233. https://doi.org/10.1006/bbrc.2000.2602
  10. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M. and Nabeshima, Y. 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236, 313-322. https://doi.org/10.1006/bbrc.1997.6943
  11. Jo, N. R., Park, C. I., Park, C. W., Shin, D. H., Hwang, Y. C., Kim, Y. H. and Park, S. N. 2012. Cellular protective effects of peanut sprout root extracts. Chem. Eng. 23, 183-189.
  12. Kim, B. W., Kim, J. I., Kim, H. R. and Byun, D. S. 2014.Anti-inflammatory effect of an ethyl acetate fraction fromMyagropsis yendoi on lipopolysaccharides-stimulated RAW264.7 cells. Kor. J. Fish Aquat. Sci. 47, 527-536.
  13. Kim, D. H., Park, S. J., Jung, J. Y., Kim, S. C. and Byun, S. H. 2009. Anti-inflammatory effects of the aqueous extract of Hwangnyeonhaedok-tang in LPS activated macrophage cells. Kor. J. Herbology 24, 39-47.
  14. Kocanova, S., Buytaert, E., Matroule, J. Y., Piette, J., Golab, J., de Witte, P. and Agostinis, P. 2007. Induction of hemeoxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy. Apoptosis 12, 731-741. https://doi.org/10.1007/s10495-006-0016-x
  15. Kundu, J. K. and Surh, Y. J. 2008. Inflammation: gearing the journey to cancer. Mutat. Res. 659, 15-30. https://doi.org/10.1016/j.mrrev.2008.03.002
  16. Lee, K. H., Nam, H. O. and Yoon, W. H. 2007. Effect of protein-bond polysaccharide isolated from Acanthopanax senthopanax in reducing the toxic effect of cisplatin. Kor. J. Pharmacogn. 38, 1-17.
  17. Lee, M. S., Lee, J., Kwon, D. Y. and Kim, M. S. 2006. Ondamtanggamibang protects neurons from oxidative stress with induction of heme oxygenase-1. J. Ethnopharmacol. 108, 294-8. https://doi.org/10.1016/j.jep.2006.05.012
  18. Lee, S. C., Kim, D. H. and Lee, H. W. 1998. Roles of nitric oxide in the ultraviolet B-induced inflammatory response of the mouse skin. Kor. J. Invest. Dermatol. 5, 127-132.
  19. Lee, S. O., Kim, M. J., Kim, D. K. and Choi, H. J. 2005. Antioxidative activities of temperature-stepwise water extracts from Inonotus obliquus. Kor. J. Soc. Food Sci. Nutr. 34, 139-147. https://doi.org/10.3746/jkfn.2005.34.2.139
  20. Lim, N. K., Lee, D. S., Yeo, S. H., Kim, Y. C. and Jeong, G. S. 2012. Involvement of heme oxygenase-induction in the neuroprotective activitiy of extract of Siegesbeckia herba in murine hippocampal HT22 cells. Kor. J. Pharmacogn. 43, 316-322.
  21. Lowenstein, C. J. and Snyder, S. H. 1992. Nitric oxide, a novel biologic messenger. Cell 70, 705-707. https://doi.org/10.1016/0092-8674(92)90301-R
  22. McDaniel, M. L., Kwon, G., Hill, J. R., Marshall, C. A. and Corbett, J. A. 1996. Cytokines and nitric oxide in islet inflammation and diabetes. Proc. Soc. Exp. Biol. Med. 211, 24-32. https://doi.org/10.3181/00379727-211-43950D
  23. Nathan, C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J. 6, 3051-3064. https://doi.org/10.1096/fasebj.6.12.1381691
  24. Ngamwongsatit, P., Banada, P. P., Panbangred, W. and Bhunia, A. K. 2008. WST-1-based cell cytotoxicity assay as a substitute for MTT-based assay for rapid detection of toxigenic Bacillus species using CHO cell line. J. Microbiol. Methods 73, 211-215. https://doi.org/10.1016/j.mimet.2008.03.002
  25. Nguyen, T., Huang, H. C. and Pickett, C. B. 2000. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J. Biol. Chem. 275, 15466-15473. https://doi.org/10.1074/jbc.M000361200
  26. Noworyta-Sokolowska, K., Gorska, A. and Golembiowska, K. 2013. LPS-induced oxidative stress and inflammatory reaction in the rat striatum. Pharmacol. Rep. 65, 863-869. https://doi.org/10.1016/S1734-1140(13)71067-3
  27. Papa, S. and Skulachev, V. P. 1997. Reactive oxygen species, mitochondria, apoptosis and aging. Mol. Cell Biochem. 174, 305-319. https://doi.org/10.1023/A:1006873518427
  28. Park, C. M., Park, J. Y., Noh, K. H., Shin, J. H. and Song, Y. S. 2011. Taraxacum officinale Weber extracts inhibit LPS-induced oxidative stress and nitric oxide production via the NF-kappaB modulation in RAW 264.7 cells. J. Ethnopharmacol. 133, 834-842. https://doi.org/10.1016/j.jep.2010.11.015
  29. Pillai, S., Oresajo, C. and Hayward, J. 2005. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation-a review. Int. J. Cosmet. Sci. 27, 17-34. https://doi.org/10.1111/j.1467-2494.2004.00241.x
  30. Radi, R., Beckman, J. S., Bush, K. M. and Freeman, B. A. 1991. Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J. Biol. Chem. 266, 4244-4250.
  31. Saw, C. L., Wu, Q., Su, Z. Y., Wang, H., Yang, Y., Xu, X., Huang, Y., Khor, T. O. and Kong, A. N. 2013. Effects of natural phytochemicals in Angelica sinensis (Danggui) on Nrf2-mediated gene expression of phase II drug metabolizing enzymes and anti-inflammation. Biopharm. Drug Dispos. 34, 303-311. https://doi.org/10.1002/bdd.1846
  32. Shan, Y., Lambrecht, R. W., Donohue, S. E. and Bonkovsky, H. L. 2006. Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin. FASEB J. 20, 2651-2653. https://doi.org/10.1096/fj.06-6346fje
  33. Shin, D. C., Kim, G. C., Song, S. Y., Kim, H. J., Yang, J. C. and Kim, B. A. 2013. Antioxidant and antiaging activities of complex supercritical fluid extracts from Dendropanax morbifera, corni fructus and lycii fructus. Kor. J. Herbology 28, 95-100.
  34. Soo, Y. B., Song, J. S., Moon, H. I. and Kim, Y. H. 2015. Effects of achyranthoside C dimethyl ester on heme oxygenase- 1 expression and NO production. J. Life Sci. 25, 976-983. https://doi.org/10.5352/JLS.2015.25.9.976
  35. Sranely, M., Princem, P. and Men, V. P. 2001. Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats. Phytither. Res. 15, 213-217. https://doi.org/10.1002/ptr.707
  36. Srisook, K., Kim, C. and Cha, Y. N. 2005. Molecular mechanisms involved in enhancing HO-1 expression: de-repression by heme and activation by Nrf2, the "one-two" punch. Antioxid. Redox. Signal. 7, 1674-1687. https://doi.org/10.1089/ars.2005.7.1674
  37. Szuster-Ciesielska, A., Daniluk, J. and Kandefr-Szerszen, M. 2001. Alcohol-related cirrosis with pancreatitis. The role of oxidative stress in the progression of the disease. Arch. Immunol. Ther. Exp. 49, 19-22.
  38. Young, I. S. and McEneny, J. 2001. Lipoprotein oxidation and atherosclerosis. Biochem. Soc. Trans. 29, 358-361. https://doi.org/10.1042/bst0290358
  39. Zamora, R., Vodovotz, Y. and Billiar, T. R. 2000. Inducible nitric oxide synthase and inflammatory diseases. Mol. Med. 6, 347-373.