Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
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Effect of Sophora flavescens Extract on Reinforcing Skin Barrier and Alleviating Inflammation

고삼 추출물의 피부장벽 강화와 염증완화 효과

  • 노경백 (바이오스펙트럼(주) 생명과학연구소) ;
  • 신승우 (바이오스펙트럼(주) 생명과학연구소) ;
  • 윤소현 (바이오스펙트럼(주) 생명과학연구소) ;
  • 원진배 (바이오스펙트럼(주) 생명과학연구소) ;
  • 오세영 (바이오스펙트럼(주) 생명과학연구소) ;
  • 김준오 ((주)신세계인터내셔날) ;
  • 박덕훈 (바이오스펙트럼(주) 생명과학연구소) ;
  • 정은선 (바이오스펙트럼(주) 생명과학연구소)
  • Received : 2020.09.01
  • Accepted : 2020.12.10
  • Published : 2020.12.30
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Abstract

Atopic dermatitis (AD) is a common and multifactorial inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. AD has a complex etiology that includes genetic, immunological, and environmental factors that cause skin barrier abnormalities and immune dysfunctions. Sophora flavescens (SF) has been used in traditional Chinese medicine, but little research has been conducted on its anti-AD efficacy. In this study, we evaluated the effect of SF extract (SFE) on improving skin barrier function and immune abnormalities, which are the main symptoms of AD. SFE has the capacity to enhance the formation of cornified envelope (CE) that plays an important role in the skin barrier function. In addition, it was confirmed that SFE increased the expression of hyaluronic acid related to skin moisture. The effect of SFE against Staphylococcus aureus (S. aureus), which increases specifically in AD lesions, confirmed that SFE inhibited the production of pro-inflammatory cytokines induced by S. aureus. Furthermore, SFE was shown to inhibit the expression of pro-inflammatory cytokines induced by substance P (SP), the cause of skin neurogenic inflammation. These results demonstrate that SFE could be one of potential candidate agent for the treatment of AD by improving the skin barrier function and immune responses.

아토피성 피부염은 피부장벽 기능장애, 염증 및 만성 소양증을 특징으로 하는 다인성의 염증성 피부질환이다. 아토피성 피부염은 유전적, 면역학적, 환경적 요인 등의 복합적인 요인으로 피부장벽 기능과 면역기능의 장애를 유발한다고 알려져 있다. 고삼 추출물은 중국전통의학에서 사용되고 있으나, 이의 항아토피 효능에 대한 연구는 거의 진행되지 않았다. 본 연구에서는 아토피성 피부염의 주요 증상인 피부장벽 기능과 면역이상 개선에 대한 고삼추출물의 효과를 평가하였다. 고삼추출물은 피부장벽 기능에서 중요한 역할을 하는 각질세포막의 형성을 강화하는 결과를 나타내었다. 또한 피부의 보습작용에 있어서 중요한 히알루론산의 발현을 증가시키는 결과를 나타내었다. 아토피성 피부염 병변에서 특이적으로 증가하는 황색포도상구균에 대한 고삼추출물의 효능도 확인하였으며, 고삼추출물이 황색포도상구균으로부터 유도된 전염증성사이토카인의 생성을 억제함을 확인하였다. 또한 피부 스트레스 등으로 부터 생성되는 신경전달 물질인 substance P에 의해 유도된 전염증성사이토카인의 발현도 억제하는 것을 확인하였다. 이러한 결과들은 고삼추출물이 피부장벽기능과 면역반응 개선을 통해 아토피 피부염 치료에 사용될 수 있는 잠재적 후보물질임을 제시한다.

Keywords

References

  1. G. Yang, J. K. Seok, H. C. Kang, Y. Y. Cho, H. S. Lee, and J. Y. Lee, Skin barrier abnormalities and immune dysfunction in atopic dermatitis, Int. J. Mol. Sci., 21(8), 2867 (2020). https://doi.org/10.3390/ijms21082867
  2. J. van Smeden and J. A. Bouwstra, Stratum corneum lipids: Their role for the skin barrier function in healthy subjects and atopic dermatitis patients, Curr. Probl. Dermatol., 49, 8 (2016). https://doi.org/10.1159/000441540
  3. O. Pacha, B. L. Sambrano, and A. A. Hebert, Skin barrier repair in eczema: A review of current understanding of pathophysiology and treatment, Curr. Dermatol. Rep., 1, 115 (2012). https://doi.org/10.1007/s13671-012-0018-6
  4. T. Gavrilova, Immune dysregulation in the pathogenesis of atopic dermatitis, Dermatitis, 29(2), 57 (2018). https://doi.org/10.1097/der.0000000000000340
  5. Y. Belkaid and T. Hand, Role of the Microbiota in Immunity and inflammation, Cell, 157(1), 121 (2014). https://doi.org/10.1016/j.cell.2014.03.011
  6. T. Andoh and Y. Kuraishi, Nitric oxide enhances substance P‐induced itch‐associated responses in mice, Br. J. Pharmacol., 138(1), 202 (2003). https://doi.org/10.1038/sj.bjp.0705004
  7. M. S. Steinhoff, B. von Mentzer, P. Geppetti, C. Pothoulakis, and N. W. Bunnett, Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease, Physiol. Rev., 94(1), 265 (2014). https://doi.org/10.1152/physrev.00031.2013
  8. E. M. Peters, M. E. Ericson, J. Hosoi, K. Seiffert, M. K. Hordinsky, J. C. Ansel, R. Paus, and T. E. Scholzen, Neuropeptide control mechanisms in cutaneous biology: physiological and clinical significance, J. Invest. Dermatol., 126(9), 1937 (2006). https://doi.org/10.1038/sj.jid.5700429
  9. D. Roosterman, T. Goerge, S. W. Schneider, N. W. Bunnett, and M. Steinhoff, Neuronal control of skin function: the skin as a neuroimmunoendocrine organ, Physiol. Rev., 86(4), 1309 (2006). https://doi.org/10.1152/physrev.00026.2005
  10. U. Pereira, N. Boulais, N. Lebonvallet, L. Lefeuvre, A. Gougerot, and L. Misery, Development of an in vitro coculture of primary sensitive pig neurons and keratinocytes for the study of cutaneous neurogenic inflammation, Exp. Dermatol., 19(10), 931 (2010). https://doi.org/10.1111/j.1600-0625.2010.01119.x
  11. C. Hosokawa, S. Takeuchi, and M. Furue, Severity scores, itch scores and plasma substance P levels in atopic dermatitis treated with standard topical therapy with oral olopatadine hydrochloride, J. Dermatol., 36(4), 185 (2009). https://doi.org/10.1111/j.1346-8138.2009.00621.x
  12. L. Misery, Atopic dermatitis and the nervous system, Clin. Rev. Allergy Immunol., 41(3), 259 (2011). https://doi.org/10.1007/s12016-010-8225-z
  13. U. Raap, S. Stander, and M. Metz, Pathophysiology of itch and new treatments, Curr. Opin. Allergy Clin. Immunol., 11(5), 420 (2011). https://doi.org/10.1097/ACI.0b013e32834a41c2
  14. S. Pavlovic, M. Daniltchenko, D. J. Tobin, E. Hagen, S. P. Hunt, B. F. Klapp, P. C. Arck, and E. M. J. Peters, Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice, J. Invest. Dermatol., 128(2), 434 (2008). https://doi.org/10.1038/sj.jid.5701079
  15. H. Murota and I. Katayama, Exacerbating factors of itch in atopic dermatitis, Allergol. Int., 66(1), 8 (2017). https://doi.org/10.1016/j.alit.2016.10.005
  16. S. Stander and T. A. Luger, NK‐1 Antagonists and itch, Handb. Exp. Pharmacol., 226, 237 (2015). https://doi.org/10.1007/978-3-662-44605-8_14
  17. C. Zeidler and S. Stander, The pathogenesis of prurigo nodularis-'Super-Itch'in exploration, Eur. J. Pain., 20(1), 37 (2016). https://doi.org/10.1002/ejp.767
  18. H. A. Jung, S. E. Jin, J. S. Park, and J. S. Choi, Antidiabetic complications and anti-alzheimer activities of sophoflavescenol, a prenylated flavonol from Sophora flavescens, and its structure-activity relationship, Phytother. Res., 25(5), 709 (2011). https://doi.org/10.1002/ptr.3326
  19. J. H. Jin, J. S. Kim, S. S. Kang, K. H. Son, H. W. Chang, and H. P. Kim, Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens, J. Ethnopharmacol., 127(3), 589 (2010). https://doi.org/10.1016/j.jep.2009.12.020
  20. H. P. Zhou, H. Lutterodt, Z. H. Cheng, and L. L. Yu, Anti-inflammatory and antiproliferative activities of trifolirhizin, a flavonoid from Sophora flavescens roots, J. Agr. Food. Chem., 57(11), 4580 (2009). https://doi.org/10.1021/jf900340b
  21. C. S. Kim, S. N. Park, S. J. Ahn, Y. W. Seo, Y. J. Lee, Y. K. Lim, M. O. Freire, E. Cho, and J. K. Kook, Antimicrobial effect of sophoraflavanone G isolated from Sophora flavescens against mutans streptococci, Anaerobe, 19, 17 (2013). https://doi.org/10.1016/j.anaerobe.2012.11.003
  22. M. Sun, H. Cao, L. Sun, S. Dong, Y. Bian, J. Han, L. Zhang, S. Ren, Y. Hu, C. Liu, L. Xu, and P. Liu, Antitumor activities of kushen: literature review, Evid. Based. Complement. Alternat. Med., 2012, 373219 (2012).
  23. T. Hasegawa, H. Shimada, T. Uchiyama, O. Ueda, M. Nakashima, and Y. Matsuoka, Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production, Lipids, 46(6), 529 (2011). https://doi.org/10.1007/s11745-011-3546-0
  24. F. Elsholz C. Harteneck, W. Muller, and K. Friedland, Calcium-a central regulator of keratinocyte differentiation in health and disease, Eur. J. Dermatol., 24(6), 650 (2014). https://doi.org/10.1684/ejd.2014.2452
  25. L. Baumann, Skin ageing and its treatment, J. Pathol., 211(2), 241 (2007). https://doi.org/10.1002/path.2098
  26. J. Ring, A. Alomar, T. Bieber, M. Deleuran, A. Fink-Wagner, C. Gelmetti, U. Gieler, J. Lipozencic, T. Luger, A. P. Oranje, T. Schafer, T. Schwennesen, S. Seidenari, D. Simon, S. Stander, G. Stingl, S. Szalai, J. C. Szepietowski, A. Taieb, T. Werfel, A. Wollenberg, and U. Darsow, European dermatology forum (EDF), European academy of dermatology and venereology (EADV), European federation of allergy (EFA), European task force on atopic dermatitis (ETFAD), European society of pediatric dermatology (ESPD), and global allergy and asthma European network (GA2LEN), guidelines for treatment of atopic eczema (atopic dermatitis) part I, J. Eur. Acad. Dermatol. Venereol., 26(8), 1045 (2012). https://doi.org/10.1111/j.1468-3083.2012.04635.x
  27. C. Lynde, K. Barber, J. Claveau, D. Gratton, V. Ho, B. Krafchik, R. Langley, D. Marcoux, E. Murray, and N. Shear, Canadian practical guide for the treatment and management of atopic dermatitis, J. Cutan. Med. Surg., 8(supple 5), 1 (2005). https://doi.org/10.1007/s10227-004-0751-y
  28. G. M. Turino and J. O. Cantor, Hyaluronan in respiratory injury and repair, Am. J. Respir. Crit. Care. Med., 167(9), 1169 (2003). https://doi.org/10.1164/rccm.200205-449PP
  29. S. Sakai, R. Yasuda, T. Sayo, O. Ishikawa, and S. Inoue, Hyaluronan exists in the normal stratum corneum, J. Invest. Dermatol., 114(6), 1184 (2000). https://doi.org/10.1046/j.1523-1747.2000.00992.x
  30. R. Tammi, J. A. Ripellino, R. U. Margolis, H. I. Maibach, and M. Tammi, Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture, J. Invest. Dermatol., 92(3), 326 (1989). https://doi.org/10.1111/1523-1747.ep12277125
  31. A. L. Byrd, Y. Belkaid and J. A. Segre, The human skin microbiome, Nat. Rev. Microbiol., 16(3), 143 (2018). https://doi.org/10.1038/nrmicro.2017.157
  32. T. Nakatsuji and R. L. Gallo, The role of the skin microbiome in atopic dermatitis, Ann. Allergy Asthma Immunol., 122(3), 263 (2019). https://doi.org/10.1016/j.anai.2018.12.003
  33. S. Higaki, M. Morohashi, T. Yamagishi, and Y. Hasegawa, Comparative study of Staphylococci from the skin of atopic dermatitis patients and from healthy subjects, Int. J. Dermatol., 38(4), 265 (1999). https://doi.org/10.1046/j.1365-4362.1999.00686.x
  34. M. Tauber, S. Balica, C. Y. Hsu, C. Jean-Decoster, C. Lauze, D. Redoules, C. Viode, A. M. Schmitt, G. Serre, M. Simon, and C. F. Paul, Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis, J. Allergy Clin. Immunol., 137(4), 1272 (2016). https://doi.org/10.1016/j.jaci.2015.07.052
  35. T. J. Guzik, M. Bzowska, A. Kasprowicz, G. Czerniawska-Mysik, K. Wójcik, D. Szmyd, T. Adamek-Guzik, and J. Pryjma, Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters, Clin. Exp. Allergy, 35(4), 448 (2005). https://doi.org/10.1111/j.1365-2222.2005.02210.x
  36. H. Y Park, C. R. Kim, I. S. Huh, M. Y. Jung, E. Y. Seo, J. H. Park, D. Y. Lee, and J. M. Yang, Staphylococcus aureus colonization in acute and chronic skin lesions of patients with atopic dermatitis, Ann. Dermatol., 25(4), 410 (2013). https://doi.org/10.5021/ad.2013.25.4.410
  37. M. R. Williams and R. L. Gallo, Evidence that human skin microbiome dysbiosis promotes atopic dermatitis, J. Invest. Dermatol., 137(12), 2460 (2017). https://doi.org/10.1016/j.jid.2017.09.010
  38. P. Meylan, C. Lang, S. Mermoud, A. Johannsen, S. Norrenberg, D. Hohl, Y. Vial, G. Prod'hom, G. Greub, M. Kypriotou, and S. Christen-Zaech, Skin colonization by Staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy, J. Invest. Dermatol., 137(12), 2497 (2017). https://doi.org/10.1016/j.jid.2017.07.834
  39. K. Iwamoto, M. Moriwaki, R. Miyake, and M. Hide, Staphylococcus aureus in atopic dermatitis: Strain-specific cell wall proteins and skin immunity, Allergol. Int., 68(3), 315 (2019).
  40. S. Pavlovic, M. Daniltchenko, D. J. Tobin, E. Hagen, S. P. Hunt, B. F Klapp, P. C. Arck, and E. M. J, Peters, Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice, J. Invest. Dermatol., 128(2), 434 (2008). https://doi.org/10.1038/sj.jid.5701079
  41. S. Pavlovic, C. Liezmann, S. M. Blois, R. Joachim, J. Kruse, N. Romani, B. F. Klapp and E. M. J. Peters, Substance P is a key mediator of stress-induced protection from allergic sensitization via modified antigen presentation, J. Immunol., 186(2), 848 (2011). https://doi.org/10.4049/jimmunol.0903878
  42. J. Salomon and E. Baran, The role of selected neuropeptides in pathogenesis of atopic dermatitis, J. Eur. Acad. Dermatol. Venereol., 22(2), 223 (2008). https://doi.org/10.1111/j.1468-3083.2007.02399.x
  43. K. H. Kim, K. C. Park, J. H. Chung, and H. R. Choi, The effect of substance P on peripheral blood mononuclear cells in patients with atopic dermatitis, J. Dermatol. Sci., 32(2), 115 (2003). https://doi.org/10.1016/S0923-1811(03)00070-7
  44. D. J. Gordon, L. S. Ostlere, and C. A. Holden, Neuropeptide modulation of Th1 and Th2 cytokines in peripheral blood mononuclear leucocytes in atopic dermatitis and non-atopic controls, Br. J. Dermatol., 137(6), 921 (1997). https://doi.org/10.1046/j.1365-2133.1997.19862067.x
  45. X. Shi, L. Wang, J. D. Clark, and W. S. Kingerya, Keratinocytes express cytokines and nerve growth factor in response to neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways, Regul. Pept., 186, 92 (2013). https://doi.org/10.1016/j.regpep.2013.08.001
  46. J. Viac, A. Gueniche, J. D. Doutremepuich, U. Reichert, A. Claudy, and D. Schmitt, Substance P and keratinocyte activation markers: an in vitro approach, Arch. Dermatol. Res., 288(2), 85 (1996). https://doi.org/10.1007/BF02505049
  47. X. He, J. Fang, L. Huang, J. Wang, and X. Huang, Sophora flavescens Ait.: Traditional usage, phytochemistry and pharmacology of an important traditional Chinese medicine, J. Ethnopharmacol., 172, 10 (2015). https://doi.org/10.1016/j.jep.2015.06.010
  48. J. L. Chang, S. P. Hu, W. Y. Wang, Y. M. Li, W. L. Zhi, S. Lu, Q. Shi, Y. Q. Wang, and Y. P. Yang, Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition, Mol. Med. Rep., 18(1), 945 (2018).
  49. P. Zhao, R. Zhou, X. Y. Zhu, Y. J. Hao, N, Li, J. Wang, Y. Niu, T. Sun, Y. X. Li, and J. Q. Yu, Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice. Int. J. Mol. Med., 36(3), 633 (2015). https://doi.org/10.3892/ijmm.2015.2260
  50. G. Xiao, S. Hao, Y. Fan, D. Han, Q. Linnan, G. Leying, W. Guanyi, Z. Chan, Y. Yan, W. Changming, Z. Yuan, Y, Guang, L. Qin, D. Xinzhong, Y. Lei, and T. Zongxiang, Matrine inhibits itching by lowering the activity of calcium channel, Sci. Rep., 8(1), 11328 (2018). https://doi.org/10.1038/s41598-018-28661-x
  51. Y. J. Niu, Q. M. Dong, and R. H. Li, Matrine regulates Th1/Th2 cytokine responses in rheumatoid arthritis by attenuating the NF-κB signaling, Cell Bio. Int., 41(6), 611 (2017). https://doi.org/10.1002/cbin.10763