DOI QR코드

DOI QR Code

비만세포에서 은행잎 플라보놀에 의한 Th2 Cytokine 발현 및 신호전달 억제 기전 효과

Suppressive effects of Th2 cytokines expression and the signal transduction mechanism in MC/9 mast cells by flavonol derived from Ginkgo biloba leaves

  • 권혜영 (국제대학교 뷰티디자인계열) ;
  • 정규진 (충남대학교 약학과) ;
  • 정광조 (대전대학교 뷰티건강관리학과)
  • 투고 : 2015.06.12
  • 심사 : 2015.08.20
  • 발행 : 2015.08.28

초록

은행잎 유래 플라보놀 성분이 갖는 항아토피 활성에 대해 입증된 바는 드물다. 이 논문에서는 MC/9 비만세포에서의 은행잎 플라보놀의 항아토피 효과를 조사하기 위하여 ELISA와 Real-time PCR, western blot으로 은행잎 플라보놀을 분석하였다. 분석 결과 IL-13, MIP-1a의 생성량은 농도 의존적으로 현저하게 감소되었으며 IL-4, IL-5, IL-13, TNF-a 유전자 발현량은 25, 50, $100{\mu}g/m{\ell}$의 농도에서 효과적으로 억제되었다. western blot 분석 결과 c-jun과 NFAT-1단백질 발현이 감소되었음을 확인하였다. 이러한 결과들은 은행잎 유래 플라보놀 성분이 NFAT-1, c-jun 전사인자의 전사를 억제함으로써 MC/9 비만세포에서의 Th2 싸이토카인의 생성을 감소시키는 효과를 갖는 것을 나타낸다. 따라서 은행잎 유래 플라보놀 성분이 아토피 피부염 치료제로서 활용가능성이 있음을 보고하고자 한다.

The effects of Flavonol contents from Ginkgo biloba leaf on anti-atopy activity have not rarely been verified. This study is to investigate the effects of flavonol on Th2 cytokine production in MC/9 mast cells. For this, flavonol was analyzed by ELISA and Real-time PCR. Analysis results showed that flavonol significantly suppressed production of Th2 cytokines(IL-13, MIP-1a) in a dose dependent manner. The mRNA expression of IL-4, IL-5, IL-13, TNF-a were effectively restrained by Flavonol at the concentration 25,50,$100{\mu}g/m{\ell}$. And decrease of expression of NFAT-1, c-jun protein was confirmed by western blot analysis. These results indicate that flavonol has effects of decreasing the Th2 cytokine production in the MC/9 mast cell causing inhibition of transcription factors such as NFAT-1, c-jun. Thus, we would like to brief that flavonol may have the applicability as therapeutic agent for atopic dermatitis.

키워드

참고문헌

  1. Daniels J and Harper J, The epidemiology of atopic dermatitis. Hosp Med, Vol. 63, No. 11, pp. 649-652. 2002. https://doi.org/10.12968/hosp.2002.63.11.1908
  2. Finlay AY, Quality of life in atopic dermatitis, J Am Acad Dermatol., Vol. 45, pp.64-66, 2001. https://doi.org/10.1067/mjd.2001.117010
  3. Lim KK, Su WP, Schroeter AL, Sabers CJ, Abraham RT, Pittelkow MR : Cyclosporine in the treatment of dermatologic disease: an update, Mayo Clin Proc, 71(12):1182-1191, 1996. https://doi.org/10.4065/71.12.1182
  4. Jeong, Seung-Il Choi, Byung-Min Yun, Young-Gab Lee, Jang-Won Jang, Seon-Il, A Noble Therapeutic Approach of Atopic dermatitis by Development of Th2 Chemokine Inhibitors from Natural Products : Inhibitory Effect of Sophora flavescens Extract in Atopic Dermatitis Model mice, NC/Nga, Herbal formula science, Vol.17 no.1, pp.141-151, 2009.
  5. Sung Ha Yun , Sang Sun Lee, Jung Eun Jang, Geon Woong Noh. Sensory Evaluation of Chungkukjangs with Herbal Extracts and Clinical Evaluation in Atopy Dermatitis Patients, The Korean journal of nutrition, Vol. 37 no.8, pp.669-674, 2004.
  6. R.Rouseff, Citrus Nutrition and Quality, American chemical society New York, pp.83-107, 1980.
  7. Sam Sik Kang, Ju Sun Kim, Wie-jong Kwak and Ki-hyup Kim, Flavonoids from the Leaves of Gin-kgo biloba, Kor. J. Pharmacogn. Vol. 21, No. 2, pp.111-120, 1990.
  8. Sam Sik Kang, Ju Sun Kim, Wie-jong Kwak and Ki-hyup Kim. Identification and Quantitative An-alysis of Flavonol Glycosides from Ginkgo bilob-a Leaves by High Performance Liquid Chromato-graphy, Kor. J. Pharmacogn., Vol. 21, No. 2, pp. 148-152,1990.
  9. Young-Suk Kwon, Hyun-Hok Cho, Seong-Yun Jeong, Sang-Youb Lee, Min-ju Kim, Sun-Ja Cho and Sang-Joon Lee, Antibacterial Activities of Gink-go Biloba Leaves Extracts Against Isolated Bact-eria from Museums, Journal of the Environmental Scie-nces, Vol. 15, No. 10, pp.983-388, 2006. https://doi.org/10.5322/JES.2006.15.10.983
  10. Jung Im Kim, Young Hee Choi, and Oh Kyung Kwon. Dyeability and Antibacterial Activity of Gin-kgo Biloba Leaf Extract Using Three Kinds of Aqueous Extraction Solvents. Journal of the Korean Society of Dyers and Finishers, Vol. 16, No. 2, pp. 8-14, 2004.
  11. In-Hwa Lee, Youn Shim, Seung-Hyun Choi, Ju-Young Park, Sung-Woo Han, Jn-Young Song, Suk-Jin Yoon. A Study on the Antimicrobial Effect of Ginkgo biloba Leaves Extracts according to Con-centrations of Ethanol for staphylococcus aureus, KSBB Journal , Vol. 21 No. 4, pp. 312-316, 2006.
  12. Ishiyama M, Miyazono Y, Sasamoto K, Ohkura Y, Ueno K. A highly water-soluble disulfonated te-trazolium salt as a chromogenic indicator for NADH as well as cell viability, Talanta, Vol. 44, No. 7, pp. 1299-1305, 1997. https://doi.org/10.1016/S0039-9140(97)00017-9
  13. Sandstrom MH, Faergemann J. Prognosis and pr-ognostic factors in adult patient with atopic derm-atitis : a long-term follow-up qeustionnaire study. Br J Dermatol. Vol. 150, pp. 103-110, 2004. https://doi.org/10.1111/j.1365-2133.2004.05711.x
  14. Ahn KM. Role of mast cells in allergic inflammat-ion and innate immunity. Korean J Pediatr. Vol. 47, pp. 1137-1141, 2004.
  15. Taketomi Y, Murakami M. Lipid networks in m-ast cell biology. Yakugaku Zasshi, Vol. 131, No. 1, pp.73-84, 2001. https://doi.org/10.1248/yakushi.131.73
  16. An HS. Textbook of pediatrics. 9th ed. Seoul: Korea Textbook Publishing Co. pp. 1104-1121, 2010.
  17. The Korean Academy of Asthma, Allergy and Cl-inical Immunology. Asthma and allergic disease. Seoul: Koonja Pub. pp.13-116, 2002.
  18. Shin HW. The experimental study on the asthma suppressive & immune response of armeniacae am-arum semen herbal-acupuncture at ST36 in OVA-induced asthma mouse. Grad School Daejeon Univ. 2006
  19. Jung-Hee Kim, Current Understanding of Atopic Dermatitis, Pediatric allergy and respiratory disease, Vol. 14, No. 1, pp. 12-23, 2004.
  20. Masuda A, Yoshikai Y, Kume H, Matsuguchi T. The Interaction between GATA Proteins and Acti-vator Protein-1 Promotes the Transcription of IL-13 in Mast Cells, J Immunol, Vol. 173, No. 9, pp. 5564-5573, 2004. https://doi.org/10.4049/jimmunol.173.9.5564
  21. Klein M, Klein-Hessling S, Palmetshofer A, Serfling E, Tertilt C, Bopp T, Heib V, Becker M, Taub-e C, Schild H, Schmitt E, Stassen M. Specific and redundant roles for NFAT transcription factors in the expression of mast cell-derived cytokines, J Immunol, Vol. 177, No. 10, pp. 6667-6674, 2006. https://doi.org/10.4049/jimmunol.177.10.6667
  22. Lewin I, Nechushtan H, Ke Q, Razin E : Regulati-on of AP-1 expression and activity in antigen sti-mulated mast cells: the role played by protein kin-ase C and the possible involvement of Fos inter-acting protein, Blood, Vol. 82, No. 12, pp. 3745-3751, 1993.
  23. Lee JS, Yun SJ, Lee JB, Kim SJ, Won YH, Lee SC. The Efficacy of Cyclosporin in Patients with Atopic Dermatitis, Korean journal of dermatology, Vol. 46, No. 2, pp. 224-230, 2008.
  24. Lee M, Park J. Regulation of NFAT activation: a potential therapeutic target for immunosuppression, Mol Cells, Vol. 22, No. 1, pp. 1-7, 2006. https://doi.org/10.1016/j.molcel.2006.03.017
  25. Park JC. Transcription Factor NFAT: The Regulation in Immune Response. KSBMB News. Vol. 20, No. 2, pp. 1-7, 2000.
  26. Rooney JW, Hoey T, Glimcher LH. Coordinate a-nd Cooperative Roles for NFAT and AP-1 in the Regulation of the Murine IL-4 Gene. Immun. Vol. 2, pp. 473-83, 1995.
  27. Im Seon Lee, Nguyen Tien Dat, Xing Fu Cai, Guanghai Shen, and Young ho Kim. Inhibitory Effect-s of Natural Products against NFAT(nuclear fact-or of activated T cells) Transcription Factor, Kor. J. Pharmacogn. Vol. 34, No. 2, pp. 150-155, 2003.
  28. Park, Gye YoungLee, Seung HeeHwangbo, BinYim, Jae-JoonLee, Choon-TaekKim, Young WhanHan, Sung KooShim, Young-SooYoo, Chul-Gyu. Proinflammatory Cytokine Expression Through $NF-{\kappa}B/I-{\kappa}B$ Pathway in Lung Epithelial Cells. Tuberculosis and Respiratory Diseases. Vol. 49, No. 3, pp. 332-342, 2000. https://doi.org/10.4046/trd.2000.49.3.332