생명과학회지 (Journal of Life Science)

  • 제28권10호
  • /
  • Pages.1170-1178
  • /
  • 2018
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

감태에서 분리된 플로로탄닌의 염증 및 알러지 억제 효과

Anti-inflammatory and Anti-allergic Effects of Phlorofucofuroeckol A and Dieckol Isolated from Ecklonia cava

  • 이승수 (경희대학교 피부생명공학센터) ;
  • 방면호 (경희대학교 피부생명공학센터) ;
  • 전형주 (장안대학교 식품영양학과) ;
  • 황태규 (우석대학교 호텔관광학과) ;
  • 양선아 (계명대학교 식품가공학과)
  • Lee, Seung-Su (Skin Biotechnology Center, Kyung Hee University) ;
  • Bang, Myun-Ho (Skin Biotechnology Center, Kyung Hee University) ;
  • Jeon, Hyeong-Ju (Department of Food & Nutrition, Jangan University) ;
  • Hwang, Taekyoo (Department of Hotel & Aviation Tourism Management, Woosuk University) ;
  • Yang, Seun-Ah (Department of Food Science and Technology, Keimyung University)
  • 투고 : 2018.08.08
  • 심사 : 2018.10.11
  • 발행 : 2018.10.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

갈조류인 감태(Ecklonia cava)의 에틸아세테이트 분획으로부터 phloroglucinol, eckol, eckstolonol, triphlorethol-A, phlorofucofuroeckol A, dieckol의 6종의 phlorotannin이 분리되었으며, NMR 및 MS분석으로 구조가 규명되었다. 감태의 주요 활성물질 분석을 위하여, 분리된 6종 물질에 대한 항산화, 항염증 및 항알러지 효과를 평가하였다. 그 중 phlorofucofuroeckol A와 triphlorethol-A가 라디컬(DPPH, ABTS) 소거 활성이 높았으며, 염증 반응에 대한 활성을 분석하기 위하여 LPS를 처리한 대식세포주인 Raw264.7에서 산화질소(NO) 생성 억제활성을 측정한 결과, phlorofucofuroeckol A의 NO 생성 억제 효과가 가장 큰 것으로 나타났다. 또한, 알러지 반응에 대한 억제활성을 분석하기 위하여 IgE-항체로 활성화시킨 비만세포주 RBL-2H3에서 분비되는 ${\beta}-Hexosaminidase$를 측정한 결과, dieckol이 농도의존적으로 가장 높은 억제 효과를 나타냈다. 따라서, 본 연구에서 항염증 및 항알러지 활성을 중심으로 분리된 6종의 플로로탄닌 중 phlorofucofuroeckol A와 dieckol은 감태의 알러지 염증 억제활성을 나타내는 주요 물질로 사료된다.

The anti-inflammatory effect of brown alga Ecklonia cava is well known, and several phlorotannins have also been reported. In this study, major active components for anti-allergy and anti-inflammation were identified by NMR and MS analysis, and the levels of effectiveness were compared. Six major phlorotannins-phloroglucinol, eckol, eckstolonol, triphlorethol-A, phlorofucofuroeckol A, and dieckol-were isolated from the ethyl acetate fraction of E. cava. In order to analyze the major active substances in E. cava, antioxidant, anti-inflammatory, and anti-allergic effects were evaluated for the six separate substances. Antioxidant capacities of each phlorotannin were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, where phlorofucofuroeckol A and triphlorethol-A had the highest radical scavenging capacity in respective radical scavenging assays. Phlorofucofuroeckol A exhibited the highest inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells among phlorotannins tested. Dieckol inhibited the release of ${\beta}-hexosaminidase$, a marker for the release of histamine in mast cells, in a dose-dependent manner in antigen-stimulated RBL-2H3 mast cells. Additionally, no cytotoxicities were observed at 1 and $2{\mu}g/ml$ in both phlorofucofuroeckol A and dieckol. These results suggest that phlorofucofuroeckol A and dieckol may play a key role in allergic inflammatory reactions.

키워드

참고문헌

  1. Ahn, G. N., Kim, K. N., Cha, S. H., Song, C. B., Lee, J. H., Heo, M. S., Yeo, I. K., Lee, N. H., Jee, Y. H. and Kim, J. S. 2007. Antioxidant activities of phlorotannins purified from Ecklonia cava on free radical scavenging using ESR and $H_2O_2$-mediated DNA damage. Eur. Food Res. Technol. 226, 71-79. https://doi.org/10.1007/s00217-006-0510-y
  2. Beckman, J. S. 1994. Peroxynitrite versus hydroxyl radical: the role of nitric oxide in superoxide-dependent cerebral injury. Ann. NY Acad. Sci. 738, 69-75.
  3. Bu, H. J., Ham, Y. M., Kim, J. M., Lee, S. J., Hyun, J. W. and Lee, N. H. 2006. Elastase and hyaluronidase inhibition activities of phlorotannins isolated from Ecklonia cava. Kor. J. Pharmacogn. 37, 92-96.
  4. Chauthe, S. K., Bharate, S. B., Sabde, S., Mitra, D., Bhutani, K. K. and Singh, I. P. 2010. Biomimetic synthesis and anti-HIV activity of dimeric phloroglucinols. Bioorg. Med. Chem. 18, 2029-2036.
  5. Cho, J. Y., Kim, A. R., Yoo, E. S., Baik, K. U. and Park, M. H. 1999. Immunomodulatory effect of arctigenin, a lignan compound, on tumour necrosis factor-alpha and nitric oxide production, and lymphocyte proliferation. J. Pharm. Pharmacol. 51, 1267-1273. https://doi.org/10.1211/0022357991777001
  6. Cho, S. M., Yang, H. J., Jeon, Y. J., Lee, C. J., Jin, Y. H., Baek, N. I., Kim, D. S., Kang, S. M., Yoon, M. S., Yong, H. I., Shimizu, M. and Han, D. S. 2012. Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols. Food Chem. 132, 1133-1142.
  7. Cho, S. Y., Park, S. J., Kwon, M. J., Jeong, T. S., Bok, S. H., Choi, W. Y., Jeong, W. I., Ryu, S. Y., Do, S. H., Lee, C. S., Song, J. C. and Jeong, K. S. 2003. Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-Κb pathway in lipopolysaccaride-stimulated macrophage. Mole. Cell. Biochem. 243, 153-160. https://doi.org/10.1023/A:1021624520740
  8. Fukuyama, Y., Kodama, M., Miura, I., Kinzyo, Z., Kido, M., Mori, H., Nakayama, Y. and Takahashi, M. 1989. Structure of an anti-plasmin inhibitor, eckol, isolated from the brown alga Ecklonia kurome Okamura and inhibitory activities of its derivatives on plasma plasmin inhibitors. Chem. Pharm. Bull. 37, 349-353. https://doi.org/10.1248/cpb.37.349
  9. Goldsby, R. A., Kindt, T. J., Osborne, B. A. and Kuby, J. 2002. Immunology, 5th ed., WH Freedman and Company, New York, USA, p553.
  10. Heo, S. J., Ko, S. C., Cha, S. H., Kang, D. H., Park, H. S., Choi, Y. U., Kim, D., Jung, W. K. and Jeon, Y. J. 2009. Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation. Toxicol. In Vitro 23, 1123-1130.
  11. Jung, W. K., Heo, S. J., Jeon, Y. J., Lee, C. M., Park, Y. M., Byun, H. G., Choi, Y. H., Park, S. G. and Choi, I. W. 2009. Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. J. Agr. Food Chem. 57, 4439-4446. https://doi.org/10.1021/jf9003913
  12. Kang, C. K., Jin, Y. B., Lee, H. K., Cha, M. J., Sohn, E. T., Moon, J. H., Park, C. W., Chun, S. H., Jung, E. S., Hong, J. S., Kim, S. B., Kim, J. S. and Kim, E. K. 2010. Brown alga Ecklonia cava attenuates type 1diabetes by activating AMPK and Akt signaling pathways. Food Chem. Toxicol. 48, 509-516.
  13. Kang, S. M., Cha, S. H., Ko, J. Y., Kang, M. C., Kim, D. K., Heo, S. J., Kim, J. S., Heu, M. S., Kim, Y. T., Jung, W. K. and Jeon, Y. J. 2012. Neuroprotective effects of phlorotannins isolated from a brown alga, Ecklonia cava, against $H_2O_2$-induced oxidative stress in murine hippocampal HT22 cells. Environ. Toxicol. Pharmacol. 34, 96-105.
  14. Kang, S. M., Kim, K. N, Lee, S. H., Ahn, G., Cha, S. H., Kim, A. D., Yang, X. D., Kang, M. C. and Jeon, Y. J. 2011. Anti-inflammatory activity of polysaccharide purified from AMG-assistant extract of Ecklonia cava in LPS-stimulated RAW264.7 macrophages. Carbohydr. Polym. 85, 80-85. https://doi.org/10.1016/j.carbpol.2011.01.052
  15. Kawakami, T. and Galli, S. J. 2002. Regulation of mast-cell and basophil function and survival by IgE. Nat. Rev. Immunol. 2, 773-786. https://doi.org/10.1038/nri914
  16. Kim, A. R., Shin, T. S., Lee, M. S., Park, J. Y., Park, K. E., Yoon, N. Y., Kim, J. S., Choi, J. S., Jang, B. C., Byun, D. S., Park, N. K. and Kim, H. R. 2009. Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties. J. Agr. Food Chem. 57, 3483-3489.
  17. Kobayashi, S. and Tanabe, S. 2006. Evaluation of the anti-allergic activity of Citrus unshiu using rast basophilic leukemia RBL-2H3 cells as well as basophils of patients with seasonal allergic rhinitis to pollen. Int. J. Mol. Med. 17, 511-515.
  18. Lee, H. K., Kang, C. K., Jung, E. S., Kim, J. S. and Kim, E. K. 2011. Antimetastatic activity of polyphenol-rich extract of Ecklonia cava through the inhibition of Akt pathway in A549 human lung cancer cells. Food Chem. 127, 1229-1236.
  19. Li, Y., Lee, S. H., Le, Q. T., Kim, M. M. and Kim, S. K. 2008. Anti-allergic effects of phlorotannins on histamine release via binding inhibition between IgE and Fc epsilonRI. J. Agr. Food Chem. 56, 12073-12080. https://doi.org/10.1021/jf802732n
  20. Lim, D., Kim, W., Lee, M. G., Heo, H. J., Chun, O. K. and Kim, D. O. 2012. Evidence for protective effects of coffees on oxidative stress-induced apoptosis through antioxidant capacity of phenolics. Food Sci. Biotechnol. 21, 1735-1744. https://doi.org/10.1007/s10068-012-0231-x
  21. Lyu, S. Y. and Park, W. B. 2005. Production of cytokine and NO by RAW 264.7 macrophages and PBMC in vitro incubation with flavonoids. Arch. Pharm. Res. 28, 573-581.
  22. Mari, Y. Y., Sawako, K., Shinya, S., Lin, Y. C., Haruhiko, T., Hisatomi, I., Keiichi, K., Yuko, C. and Takafumi, U. 2013, Isolation and structural determination of two novel phlorotannins from the brown alga Ecklonia kurome Okamura, and their radical scavenging activities. Mar. Drugs 11, 165-183. https://doi.org/10.3390/md11010165
  23. Matheis, G., Sheman, M. P., Buckberg, G. D., Haybron, D. M., Young, H. H. and Ignarro, L. J. 1992. Role of L-arginine-nitric oxide pathway in myocardial reoxygenation injury. Am. J. Physiol. 262, H616-H620.
  24. Matsuda, H., Morikawa, T., Ueda, K., Managi, H. and Yoshikawa, M. 2002. Labdane-type diterpenes with inhibitory effects on increase in vascular permeability and nitric oxide production from Hedychium coronarium. Bioorg. Med. Chem. 10, 2527-2534. https://doi.org/10.1016/S0968-0896(02)00121-9
  25. Matsuda, H., Tewtrakul, S., Morikawa, T., Nakamura, A. and Yoshikawa, M. 2004. Anti-allergic principles from Thai zedoary: structural requirements of curcuminoids for inhibition of degranulation and effect on the release of TNFalpha and IL-4 in RBL-2H3 cells. Bioorg. Med. Chem. 12, 5891-5898. https://doi.org/10.1016/j.bmc.2004.08.027
  26. 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
  27. Mwangi, H. M., Njue, W. M., Onani, M. O., Thovhoghi, T. and Mabusela, W. T. 2017, Phlorotannins and a sterol isolated from a brown alga Ecklonia maxima, and their cytotoxic activity against selected cancer cell lines HeLa, H157 and MCF 7. Inter. J Chem. doi: 10.15761/IJC.1000120.4.
  28. Myung, C. S., Shin, H. C., Bao, H. Y., Yeo, S. J., Lee, B. H. and Kang, J. S. 2005. Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice: Possible involvement of the inhibition of acetylcholinesterase. Arch. Pharm. Res. 28, 691-698. https://doi.org/10.1007/BF02969360
  29. Oskoueian, E., Abdullah, N., Saad, W. Z., Omar, A. R., Ahmad, S., Kuan, W. B., Zolkifli, N. A., Hendra, R. and Ho, Y. W. 2011. Antioxidant, anti-inflammatory and anticancer activities of methanolic extracts from Jatropha curcas Linn. J. Med. Plants Res. 5, 49-57.
  30. Rees, D. D., Cellek, S., Palmer, R. M. and Moncada, S. 1990. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem. Biophy. Res. Commun. 173, 541-547. https://doi.org/10.1016/S0006-291X(05)80068-3
  31. Shibata, T., Ishimaru, K., Kawaguchi, S., Yoshikawa, H. and Hama, Y. 2008. Antioxidant activities of phlorotannins isolated from Japanese Laminariaceae. J. Appl. Phycol. 20, 705-711. https://doi.org/10.1007/s10811-007-9254-8
  32. Siddhuraju, P. 2007. Antioxidant activity of polyphenolic compounds extracted from deffated raw and dry heated Tamarindus indica seed coat. LWT-Food Sci. Technol. 40, 982-990.
  33. Stefanovic-Racic, S., Stadler, J. and Evan, C. H. 1993. Nitric oxide and arthritis. Arthritis Rheum. 36, 1036-1044.
  34. Sun, B., Morikawa, T., Matsuda, H., Tewtrakul, S., Wu, L. J., Harima, S. and Yoshikawa, M. 2004. Structures of new ${\beta}$-carboline-type alkaloids with antiallergic effects from Stellaria dichotoma (1,2). J. Nat. Prod. 67, 1464-1469. https://doi.org/10.1021/np040080a
  35. Wedemeyer, J., Tsai, M. and Galli, S. J. 2000. Roles of mast cells and basophils in innate and acquired immunity. Curr. Opin. Immunol. 12, 624-631.
  36. Yoo, K. M., Kim, D. O. and Lee, C. Y. 2007. Evaluation of different methods of antioxidant measurement. Food Sci. Biotechnol. 16, 177-182.
  37. Yoon, N. Y., Chung, H. Y., Kim, H. R. and Choi, J. S. 2008. Acetyl- and butyrylcholinesterase inhibitory activities of sterols and phlorotannins from Ecklonia stolonifera. Fish Sci. 7, 200-207.
  38. Zhang, C., Li, Y., Qian, Z. J., Lee, S. H., Li, Y. X. and Kim, S. K. 2011. Dieckol from Ecklonia cava regulates invasion of human fibrosarcoma cells and modulates MMP-2 and MMP-9 expression via NF-${\kappa}$B pathway. Evid. Based Complement. Alternat. Med. 2011, 1-8.