The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
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Effects of Raphani Semen Ethanol Extracts on Skin Inflammation in HaCaT Keratinocytes

나복자(萊菔子) 에탄올 추출물이 HaCaT 피부각질형성세포에서 피부염증 감소에 미치는 영향

  • Kim, Keun-Lip (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Sangji University) ;
  • Hong, Chul-Hee (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Sangji University) ;
  • Lee, Kyou-Young (Department of Ophthalmology, Otolaryngology & Dermatology, College of Korean medicine, Sangji University)
  • 김근립 (상지대학교 한의과대학 안이비인후피부과학교실) ;
  • 홍철희 (상지대학교 한의과대학 안이비인후피부과학교실) ;
  • 이규영 (상지대학교 한의과대학 안이비인후피부과학교실)
  • Received : 2022.04.06
  • Accepted : 2022.04.25
  • Published : 2022.05.25
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Abstract

목적 : 본 연구는 인간피부각질형성세포(HaCaT keratinocytes) 모델을 TNF-α와 IFN-γ로 자극하여 내복자(萊菔子)의 피부염증 감소 및 만성 염증성 질환에 미치는 영향을 알아보고자 하였다. 방법 : 내복자(萊菔子) 에탄올 추출물(RSE)이 세포생존율에 미치는 영향을 확인하기 위하여 MTT assay를 시행하였다. 또한 RSE가 TNF-α와 IFN-γ로 자극한 HaCaT 세포에서 p-IκBα, p-ERK, p-JAK2, p-STAT1, p-STAT6의 발현과 periostin, TSLP 단백질 발현에 미치는 영향을 확인하였다. 결과 : RSE는 200㎍/㎖ 이하에서 세포 독성을 보이지 않았고, HaCaT keratinocytes에서 TNF-α와 IFN-γ자극에 의하여 증가된 IκBα, ERK의 인산화를 억제하였다. 또한 JAK2와 STAT1, STAT6의 인산화를 억제하였으며, periostin과 TSLP의 발현을 감소시켰다. 결론 : RSE는 HaCaT keratinocytes에서 pro-inflammatory cytokines 및 transcription factors의 발현을 감소시켜 피부염증 감소 효능을 보였고, 만성 염증성 질환에서 내복자(萊菔子)의 사용 가능성을 확인하였다.

Keywords

References

  1. Pasparakis M, Haase I, Nestle FO. Mechanisms regulating skin immunity and inflammation. Nature. 2014;14(5): 289-301.
  2. Nakajima S, Nomura T, Common J, kabashima K. Insights into atopic dermatitis gained from genetically defined mouse models. Journal of Allergy and Clinical Immunology. 2019;143(1):13-25. https://doi.org/10.1016/j.jaci.2018.11.014
  3. Guttman-Yassky E, Waldman A, Ahluwalia J, Ong PY, Eichenfield LF. Atopic dermatits : Pathogenesis. Seminars in cutaneous medicine and surgery. 2017;36(3):100-3. https://doi.org/10.12788/j.sder.2017.036
  4. Khamees AH. Phytochemical and pharmacological analysis for seeds of two varieties of Iraqi Raphanus sativus. International Journal of Pharmaceutical Sciences Review and Research. 2017;43(1):237-42.
  5. KIM CM, Lee YC, Lee JC. The Effects of Sinapis Semen, Raphani Semen, and mixture decoction on the Asthmatic Mouse Model. The Korea Journal of Herbology. 2013; 28(6):15-23. https://doi.org/10.6116/KJH.2013.28.6.15
  6. Choi KC, Cho SW, Kook SH, Chun SR, Bhattarai G, Poudel SB, et al. Intestinal anti-inflammatory activity of the seeds of Raphanus sativus L. in experimental ulcerative colitis models. Journal of Ethnopharmacology. 2016;179:55-65. https://doi.org/10.1016/j.jep.2015.12.045
  7. Lee BR. Anti-inflammatory mechanism of allyl isothiocyanate, a chemical ingredient of Raphani semen. Graduate school of Wonkwang University. 2009:1-43.
  8. Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002;109:S81-96. https://doi.org/10.1016/S0092-8674(02)00703-1
  9. Huang P, Han J, Hui L. MAPK signaling in inflammation-associated cancer development. Protein Cell. 2010;1(3):218-26. https://doi.org/10.1007/s13238-010-0019-9
  10. Goodridge HS, Harnett W, Liew FY, Harnett MM. Differential regulation of interleukin-12 p40 and p35 induction via Erk mitogen-activated protein kinase-dependent and - independent mechanisms and the implications for bioactive IL-12 and IL-23 responses. Immunology. 2003;109(3): 415-25. https://doi.org/10.1046/j.1365-2567.2003.01689.x
  11. Feng GJ, Goodridge HS, Harnett MM, Wei XQ, Nikolaev AV, Higson AP, et al. Extracellular signal-related kinase(ERK) and p38 mitogen-activated protein(MAP) kinases differentially regulate the lipopolysaccharide-mediated induction of inducible nitric oxide synthase and IL-12 in macrophages: Leishmania phosphoglycans subvert macrophage IL-12 production by targeting ERK MAP kinase. The Journal of Immunology. 1999;163(12):6403-12.
  12. Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2(3):1-8.
  13. Lejeune D, Dumoutier L, Constantinescu S, Kruijer W, Schuringa JJ, Renauld JC. Interleukin-22(IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line. Pathways that are shared with and distinct from IL-10. Journal of Biological Chemistry. 2002;277(37):33676-82. https://doi.org/10.1074/jbc.M204204200
  14. Wick KR, Berton MT. IL-4 induces serine phosphorylation of the STAT6 transactivation domain in B lymphocytes. Molecular Immunology. 2000;37(11):641-52. https://doi.org/10.1016/S0161-5890(00)00088-2
  15. Shiraishi H, Masuoka M, Ohta S, Suzuki S, Arima K, Taniguchi K, et al. Periostin contributes to the pathogenesis of atopic dermatitis by inducing TSLP production from keratinocytes. Allergology International. 2012;61(4):563-72. https://doi.org/10.2332/allergolint.10-OA-0297
  16. Masuoka M, Shiraishi H, Ohta S, Suzuki S, Arima K, Aoki S, et al. Periostin promotes chronic allergic inflammation in response to Th2 cytokines. The Journal of Clinical Investigation. 2012;122(7):2590-600. https://doi.org/10.1172/JCI58978
  17. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nature Immunology. 2002;3(7):673-80. https://doi.org/10.1038/ni805
  18. Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ. Distinct signal codes generate dendritic cell functional plasticity. Science Signaling. 2010;3(105):1-15.
  19. Herbology Editorial Committee of Korean Medicine schools. Boncho-hak. Seoul: Younglimsa. 2020:408,409.
  20. Ahmed F, Hasan I, Chishti DK, Ahmad H. Antibacterial Activity of Raphanus Sativus Linn. Seed Extract. Global Journal of Medical Research. 2012;12(11):25-34.
  21. Asif M, Yousaf HM, Saleem M, Hussain L, Mahrukh, Zarzour RA, et al. Raphanus Sativus Seeds Oil Arrested In Vivo Inflammation and Angiogenesis Through Down-Regulation of TNF-α. Current Pharmaceutical Biotechnology. 2022;23(5): 728-39. https://doi.org/10.2174/1389201022666210702120956
  22. M Umamaheswari, MP Ajith, K Asokkumar, T Sivashanmugam, V Subhadradevi, P Jagannath. In Vitro angiotensin converting enzyme inhibitory and antioxidant activities of methanolic seed extract of Apium graveolens linn. Annals of Biological Research. 2012;3(3):1274-82.
  23. Myung SH, Lee HI, Kim YS. Effects of Bambusae Caulis and Raphani Semen on Streptozotocin-treated Rats. The Korea Journal of Herbology. 1999;36(5):79-86.
  24. Salai Bojan M, Rajappa R, Vijayakumar D.R.K., Gopalan, J. Protective effect of Raphanus sativus on D-galactosamine induced nephrotoxicity in rats. Nutrition Clinique et Metabolisme. 2016;30(1):22-8. https://doi.org/10.1016/j.nupar.2015.12.002
  25. Dande P, A Vaidya, and P Arora. LAXATIVE ACTIVITY OF RAPHANUS SATIVUS L. LEAF. Asian Journal of Pharmaceutical and Clinical Research. 2014;7(7):120-4.
  26. Jeon HS, Yang DW, Lee NH, Ahn MJ, Kim GO. Inhibitory Effect of Black Radish (Raphanus sativus L. var.niger) Extracts on Lipopolysaccharide-Induced Inflammatory Response in the Mouse Monocyte/Macrophage-Like Cell Line RAW 264.7. Preventive Nutrition and Food Science. 2020;25(4):408-21. https://doi.org/10.3746/pnf.2020.25.4.408
  27. Ibrahim HYE, Abdel-Mogib M, Mohamed ME. Insecticidal Activity of Radish, Raphanus sativus Linn.(Brassicaceae) Roots Extracts. Journal of Plant Protection and Pathology. 2020;11(1):53-8. https://doi.org/10.21608/jppp.2020.79164
  28. Korean Dermatological Association Textbook Compilation Committee. Dermatology. Seoul:Ryo Moon Gak P. Co. 2008:11-8.
  29. Boukamp P, Petrussevska RT, Breitkreutz D, Hornung J, Markham A, Fusenig NE. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. Journal of Cell Biology. 1988;106(3):761-71. https://doi.org/10.1083/jcb.106.3.761
  30. Grewe M, Walther S, Gyufko K, Czech W, Schopf E, Krutmann J. Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. Journal of Investigative Dermatology. 1995;105(3):407-10. https://doi.org/10.1111/1523-1747.ep12321078
  31. Thepen T, Langeveld-Wildschut EG, Bihari IC, van Wichen DF, van Reijsen FC, Mudde GC, et al. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ : an immunohistochemical study. Journal of Allergy and Clinical Immunology. 1996;97(3):828-37. https://doi.org/10.1016/S0091-6749(96)80161-8
  32. Grewe M, Gyufko K, Schopf E, Krutmann J. Lesional expression of interferon-gamma in atopic eczema. Lancet. 1994;343(8888): 25,26. https://doi.org/10.1016/S0140-6736(94)90879-6
  33. Choi JH, Jin SW, Park BH, Kim HG, Khanal T, Han HJ, et al. Cultivated ginseng inhibits 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice and TNF-α/IFN-γ-induced TARC activation in HaCaT cells. Food and Chemical Toxicology. 2013;56:195-203. https://doi.org/10.1016/j.fct.2013.02.037
  34. Jung MR, Lee TH, Bang MH, Kim H, Son Y, Chung DK, et al. Suppression of thymus-and activation-regulated chemokine(TARC/CCL17) production by 3-O-β-D-glucopyanosylspinasterol via blocking NF-κB and STAT1 signaling pathways in TNF-α and IFN-γ-induced HaCaT keratinocytes. Biochemical and Biophysical Research Communications. 2012;427(2):236-41. https://doi.org/10.1016/j.bbrc.2012.08.087
  35. Kong L, Liu J, Wang J, Luo Q, Zhang H, Liu B, et al. Icariin inhibits TNF-α/IFN-γ induced inflammatory response via inhibition of the substance P and p38-MAPK signaling pathway in human keratinocytes. International Immunopharmacology. 2015;29(2):401-7. https://doi.org/10.1016/j.intimp.2015.10.023
  36. Z Chen, J Hagler, V J Palombella, F Melandri, D Scherer, D Ballard, et al. Signal-induced site specific phosphorylation targets IκBa to the ubiquitin proteasome pathway. Genes & Development. 1995;9 (13):1586-97. https://doi.org/10.1101/gad.9.13.1586
  37. S Yamaoka, G Courtois, C Bessia, ST Whiteside, R Weil, F Agou, et al. Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation. Cell. 1998;93(7):1231-40. https://doi.org/10.1016/S0092-8674(00)81466-X
  38. Yang Y, Kim SC, Yu T, Yi YS, Rhee MH, Sung GH, et al. Functional roles of p38 mitogen-activated protein kinase in macrophage-mediated inflammatory responses. Mediators of Inflammation. 2014;2014:1-13.
  39. Nathan Lu, Charles J Malemud. Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression. International Journal of Molecular Sciences. 2019;20(15):1-18.
  40. Po-Wen Liu, Mei-Fang Chen, Andy Po-Yi Tsai, Tony J F Lee. STAT1 mediates oroxylin a inhibition of iNOS and pro-inflammatory cytokines expression in microglial BV-2 cells. PLoS One. 2012;7(12):1-18.
  41. Wei J, Lian H, Zhong B, Shu HB. Parafibromin Is a Component of IFN-γ-Triggered Signaling Pathways That Facilitates JAK1/2-Mediated Tyrosine Phosphorylation of STAT1. The Journal of Immunology. 2015;195(6):2870-8. https://doi.org/10.4049/jimmunol.1501111
  42. Haase P, Mokada-Gopal L, Radtke D, Voehringer D. Modulation of the humoral immune response by constitutively active STAT6 expression in murine B cells. European Journal of Immunology. 2020;50(4):558-67. https://doi.org/10.1002/eji.201948313
  43. Mishra skat, Wheeler JJ, Pitake S, Ding H, Jiang C, Fukuyama T, et al. Periostin Activation of Integrin Receptors on Sensory Neurons Induces Allergic Itch. Cell Reports. 2020;31(1):1-20.
  44. Choi WH, Park TY, Kim SY, Yu R, Ban JE, Yang S, et al. Serum periostin levels and squamous cell carcinoma-related antigen levels in children with atopic dermatitis. Allergy Asthma & Respiratory Diseases. 2017;5(2):73-8. https://doi.org/10.4168/aard.2017.5.2.73
  45. Sims JE, Williams DE, Morrissey PJ, Garka K, Foxworthe D, Price V, et al. Molecular cloning and biological characterization of a novel murine lymphoid growth factor. Journal of Experimental Medicine. 2000;192(5):671-80. https://doi.org/10.1084/jem.192.5.671