생명과학회지 (Journal of Life Science)

  • 제22권9호
  • /
  • Pages.1254-1260
  • /
  • 2012
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

HaCaT 각질형성세포에서 TNF-α에 의하여 유도되는 염증 발현에 대한 부위별 모링가 추출물의 억제 효과

Suppression of TNF-α-induced Inflammation by Extract from Different Parts of Moringa in HaCaT Cells

  • 이효진 (대구가톨릭대학교 의용생체공학연구소) ;
  • 장영채 (대구가톨릭대학교 의용생체공학연구소)
  • Lee, Hyo-Jin (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Chang, Young-Chae (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine)
  • 투고 : 2012.08.11
  • 심사 : 2012.08.29
  • 발행 : 2012.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

모링가(Moringa oleifera Lam.)는 항알러지 약물로써 식용 가능한 식물이다. 본 연구에서 부위별 모링가의 피부 보호제로서의 가능성을 확인하기 위하여, TNF-${\alpha}$로 염증을 유도한 각질형성세포에서 모링가의 씨, 뿌리, 잎과 열매 메탄올 추출물의 항염증 효과를 비교 실험하였다. 피부세포의 콜라겐 분해 관련인자인 MMP-2, MMP-9의 효소 활성을 측정한 결과 모든 부위별 모링가 추출물이 MMP-9의 효소 활성을 감소시켰다. 특히 모링가 뿌리 추출물은 낮은 농도에도 MMP-9을 효과적으로 감소시켰으며 MMP-2의 효소활성 억제에도 효과가 관찰되었다. 또한 피부 염증관련 인자로 알려진 iNOS와 COX-2의 단백질 발현을 측정한 결과, COX-2의 단백질 발현은 모링가 잎을 제외한 뿌리, 씨앗, 열매 추출물에 의해 억제되었다. 그 중 모링가 뿌리 추출물은 낮은 농도에서도 COX-2 단백질의 발현을 억제시켰다. 그러나 iNOS는 부위별 모링가 추출물에 의한 단백질 발현의 변화가 없는 것으로 나타났다. 뿐만 아니라 피부 염증을 일으키는 cytokine으로 알려진 IL-6의 mRNA발현을 확인한 결과 TNF-${\alpha}$에 의해 증가된 IL-6 발현을 모링가 뿌리 추출물이 효과적으로 억제 시키는 것을 확인할 수 있었다. 이상의 결과로 미루어 보아 부위별 모링가 추출물 중 뿌리 추출물에서 가장 피부노화 억제와 항 염증 효과가 높을 것으로 사료되며, 식물 유래의 피부 보호제 제품 개발에 있어 유용한 원료로 사용될 수 있을 것으로 생각된다.

The moringa (Moringa oleifera Lam.) plant is used both as food and an anti-allergic agent. In this study, we investigated skin protection effects of methanol extracts from the root, seed, fruit, and leaves of moringa in HaCaT keratinocyte cells. To investigate the pharmacological potential of various moringa extracts on TNF-${\alpha}$-induced collagen degradation in HaCaT cells, we measured the activity of matrix metallopeptidase-9,2 (MMP-9,2) by zymography analysis. Our results showed that all the moringa extracts inhibit the TNF-${\alpha}$-induced enzyme activity of MMP-9. In particular, moringa root extracts significantly suppressed MMP-9 and MMP-2 in a dose-dependent manner. Next, to investigate the anti-inflammation effect of the moringa extracts, we examined cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) expression of the extracts. The results showed that both the root extracts and the seed extracts decreased the TNF-${\alpha}$-induced expression of COX-2. In addition, the root and leaf extracts reduced the expression of IL-6. However, none of the moringa extracts affected the expression of iNOS. The results suggest that moringa root extracts down-regulate MMP-9, COX-2, and IL-6 and that the root extracts offer superior skin protection effects compared with other extracts of moringa in HaCaT cells.

키워드

참고문헌

  1. Aktan, F. 2004. iNOS-mediated nitric oxide production and its regulation. Life Sci. 75, 639-653. https://doi.org/10.1016/j.lfs.2003.10.042
  2. Anggakusuma, Yanti and Hwang, J. K. 2010. Effects of macelignan isolated from Myristica fragrans Houtt. on UVB-induced matrix metalloproteinase-9 and cyclooxygenase-2 in HaCaT cells. J. Dermatol. Sci. 57, 114-122. https://doi.org/10.1016/j.jdermsci.2009.10.005
  3. Anwar, F., Latif, S., Ashraf, M. and Gilani, A. H. 2007. Moringa oleifera: a food plant with multiple medicinal uses. Phytother. Res. 21, 17-25. https://doi.org/10.1002/ptr.2023
  4. Atawodi, S. E., Atawodi, J. C., Idakwo, G. A., Pfundstein, B., Haubner, R., Wurtele, G., Bartsch, H. and Owen, R. W. 2010. Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of Moringa oleifera Lam. J. Med. Food 13, 710-716. https://doi.org/10.1089/jmf.2009.0057
  5. Bachmeier, B. E. and Nerlich, A. G. 2002. Immunohistochemical pattern of cytokeratins and MMPs in human keratinocyte cell lines of different biological behaviour. Int. J. Oncol. 20, 495-499.
  6. Beissert, S., Cavazzana, I., Mascia, F., Meroni, P., Pastore, S., Tessari, G. and Girolomoni, G. 2006. Mechanisms of immune- mediated skin diseases: an overview. Clin. Exp. Rheumatol. 24, S1-6.
  7. Buckman, S. Y., Gresham, A., Hale, P., Hruza, G., Anast, J., Masferrer, J. and Pentland, A. P. 1998. COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer. Carcinogenesis 19, 723-729. https://doi.org/10.1093/carcin/19.5.723
  8. Diker-Cohen, T., Koren, R., Liberman, U. A. and Ravid, A. 2003. Vitamin D protects keratinocytes from apoptosis induced by osmotic shock, oxidative stress, and tumor necrosis factor. Ann. N. Y. Acad. Sci. 1010, 350-353. https://doi.org/10.1196/annals.1299.064
  9. Eberhardt, W., Huwiler, A., Beck, K. F., Walpen, S. and Pfeilschifter, J. 2000. Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J. Immunol. 165, 5788-5797. https://doi.org/10.4049/jimmunol.165.10.5788
  10. Faizi, S., Siddiqui, B. S., Saleem, R., Siddiqui, S., Aftab, K. and Gilani, A. H. 1994. Isolation and structure elucidation of new nitrile and mustard oil glycosides from Moringa oleifera and their effect on blood pressure. J. Nat. Prod. 57, 1256-1261. https://doi.org/10.1021/np50111a011
  11. Faizi, S., Siddiqui, B. S., Saleem, R., Siddiqui, S., Aftab, K. and Gilani, A. H. 1995. Fully acetylated carbamate and hypotensive thiocarbamate glycosides from Moringa oleifera. Phytochemistry 38, 957-963. https://doi.org/10.1016/0031-9422(94)00729-D
  12. Grewe, M., Trefzer, U., Ballhorn, A., Gyufko, K., Henninger, H. and Krutmann, J. 1993. Analysis of the mechanism of ultraviolet (UV) B radiation-induced prostaglandin E2 synthesis by human epidermoid carcinoma cells. J. Invest. Dermatol. 101, 528-531. https://doi.org/10.1111/1523-1747.ep12365904
  13. Guevara, A. P., Vargas, C., Sakurai, H., Fujiwara, Y., Hashimoto, K., Maoka, T., Kozuka, M., Ito, Y., Tokuda, H. and Nishino, H. 1999. An antitumor promoter from Moringa oleifera Lam. Mutat. Res. 440, 181-188. https://doi.org/10.1016/S1383-5718(99)00025-X
  14. Han, Y. P., Tuan, T. L., Hughes, M., Wu, H. and Garner, W. L. 2001. Transforming growth factor-beta - and tumor necrosis factor-alpha -mediated induction and proteolytic activation of MMP-9 in human skin. J. Biol. Chem. 276, 22341-22350. https://doi.org/10.1074/jbc.M010839200
  15. Heck, D. E., Laskin, D. L., Gardner, C. R. and Laskin, J. D. 1992. Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. J. Biol. Chem. 267, 21277-21280.
  16. Hur, S., Lee, Y. S., Yoo, H., Yang, J. H. and Kim, T. Y. 2010. Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-kappaB nuclear localization. J. Dermatol. Sci. 59, 163-169. https://doi.org/10.1016/j.jdermsci.2010.07.001
  17. Ishida, H., Ray, R. and Ray, P. 2008. Sulfur mustard downregulates iNOS expression to inhibit wound healing in a human keratinocyte model. J. Dermatol. Sci. 49, 207-216. https://doi.org/10.1016/j.jdermsci.2007.09.002
  18. Isoherranen, K., Punnonen, K., Jansen, C. and Uotila, P. 1999. Ultraviolet irradiation induces cyclooxygenase-2 expression in keratinocytes. Br. J. Dermatol. 140, 1017-1022. https://doi.org/10.1046/j.1365-2133.1999.02897.x
  19. Johansson, N., Westermarck, J., Leppa, S., Hakkinen, L., Koivisto, L., Lopez-Otin, C., Peltonen, J., Heino, J. and Kahari, V. M. 1997. Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth factor beta. Cell Growth Differ. 8, 243-250.
  20. Kahari, V. M. and Saarialho-Kere, U. 1997. Matrix metalloproteinases in skin. Exp. Dermatol. 6, 199-213. https://doi.org/10.1111/j.1600-0625.1997.tb00164.x
  21. Kean, W. F. and Buchanan, W. W. 2005. The use of NSAIDs in rheumatic disorders 2005: a global perspective. Inflammopharmacology 13, 343-370. https://doi.org/10.1163/156856005774415565
  22. Kobayashi, T., Hattori, S., Nagai, Y., Tajima, S. and Nishikawa, T. 1998. Differential regulation of MMP-2 and MMP-9 gelatinases in cultured human keratinocytes. Dermatology 197, 1-5. https://doi.org/10.1159/000017967
  23. Kwon, D. J., Bae, Y. S., Ju, S. M., Goh, A. R., Choi, S. Y. and Park, J. 2011. Casuarinin suppresses TNF-alpha-induced ICAM-1 expression via blockade of NF-kappaB activation in HaCaT cells. Biochem. Biophys. Res. Commun.
  24. Lawrence, T., Willoughby, D. A. and Gilroy, D. W. 2002. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat. Rev. Immunol. 2, 787-795. https://doi.org/10.1038/nri915
  25. Oki, T., Masuda, M., Kobayashi, M., Nishiba, Y., Furuta, S., Suda, I. and Sato, T. 2002. Polymeric procyanidins as radical- scavenging components in red-hulled rice. J. Agric. Food Chem. 50, 7524-7529. https://doi.org/10.1021/jf025841z
  26. Rathi, B. S., Bodhankar, S. L. and Baheti, A. M. 2006. Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing in albino rats. Indian J. Exp. Biol. 44, 898-901
  27. Roig, R., Cascon, E., Arola, L., Blade, C. and Salvado, M. J. 2002. Procyanidins protect Fao cells against hydrogen peroxide-induced oxidative stress. Biochim. Biophys. Acta. 1572, 25-30. https://doi.org/10.1016/S0304-4165(02)00273-8
  28. Sakai, M., Shimizu, Y., Nagatsu, I. and Ueda, H. 1996. Immunohistochemical localization of NO synthases in normal human skin and psoriatic skin. Arch. Dermatol. Res. 288, 625-627. https://doi.org/10.1007/BF02505267
  29. Schaffer, M. R., Tantry, U., van Wesep, R. A. and Barbul, A. 1997. Nitric oxide metabolism in wounds. J. Surg. Res. 71, 25-31. https://doi.org/10.1006/jsre.1997.5137
  30. Sirsjo, A., Karlsson, M., Gidlof, A., Rollman, O. and Torma, H. 1996. Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes. Br. J. Dermatol. 134, 643-648. https://doi.org/10.1111/j.1365-2133.1996.tb06963.x
  31. Staples, G. and Herbst, D. R. 2005. A tropical garden flora : plants cultivated in the Hawaiian Islands and other tropical places. Honolulu, Hawai'i: Bishop Museum Press. p xxiv, 908 p.
  32. Ursini, F., Rapuzzi, I., Toniolo, R., Tubaro, F. and Bontempelli, G. 2001. Characterization of antioxidant effect of procyanidins. Methods Enzymol. 335, 338-350. https://doi.org/10.1016/S0076-6879(01)35256-4
  33. Vane, J. R. 1971. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New Biol. 231, 232-235. https://doi.org/10.1038/newbio231232a0
  34. Williams, T. J. 1983. Interactions between prostaglandins, leukotrienes and other mediators of inflammation. Br. Med. Bull. 39, 239-242.
  35. Woessner, J. F. Jr. 2002. MMPs and TIMPs--an historical perspective. Mol. Biotechnol. 22, 33-49. https://doi.org/10.1385/MB:22:1:033
  36. Yayeh, T., Oh, W. J., Park, S. C., Kim, T. H., Cho, J. Y., Park, H. J., Lee, I. K., Kim, S. K., Hong, S. B., Yun, B. S. and Rhee, M. H. 2011. Phellinus baumii ethyl acetate extract inhibits lipopolysaccharide-induced iNOS, COX-2, and proinflammatory cytokine expression in RAW264.7 cells. J. Nat. Med. 66, 49-54.

피인용 문헌

  1. Anti-Diabetic, Alcohol-Metabolizing, and Hepatoprotective Activities of Moringa (Moringa oleifera Lam.) Leaf Extracts vol.45, pp.6, 2016, https://doi.org/10.3746/jkfn.2016.45.6.819
  2. Quality Characteristics of Muffins Added with Moringa (Moringa oleifera Lam.) Leaf Powder vol.45, pp.6, 2016, https://doi.org/10.3746/jkfn.2016.45.6.872
  3. Antioxidation, Physicochemical, and Sensory Characteristics of Sulgidduck Fortified with Water Extracts from Moringa oleifera Leaf vol.31, pp.3, 2015, https://doi.org/10.9724/kfcs.2015.31.3.335
  4. Effect ofMoringa oleiferaLeaf on Antioxidant and Quality Characteristics of the Korean Traditional Rice Cake Sulgidduk vol.41, pp.2, 2017, https://doi.org/10.1111/jfpp.12820