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Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin lesions in mice

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Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized with high heterogeneity. Recent studies have suggested that it is driven by both terminal keratinocyte differentiation defects and type 2 immune responses. The mainstay steroid topical therapy has severe side effect and new treatment is in demand. Isoliquiritigenin (ISLG) is a small phenolic bioactive molecule from licorice that has shown multiple pharmacological effects against cancer, inflammatory disorder, and cardiovascular diseases. ISLG was evaluated in AD-like lesion model induced by the repetitive application of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Overall symptom score, serological and molecular changes of the skin lesions were evaluated. ISLG could ameliorate the overall manifestation of AD-like symptoms including scratching behavior incidence and skin lesion severity. At blood level, ISLG significantly suppressed the DNCB-induced IgE and Th2 cytokines up-regulation. At skin lesion site, ISLG also inhibited DNCB-induced pro-inflammatory cytokines like TNF-α, IL-6 as well as IL-4 expressions. In a human monocyte model THP-1, ISLG suppressed the up-regulation of CD86 and CD54 and abolished the DNCB-induced p38-α and ERK activation, suggesting a molecular mechanism for ISLG therapy. This study indicated that ISLG could be a potential therapeutic agent for the treatment of AD.

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References

  1. Allam JP, Novak N (2006) The pathophysiology of atopic eczema. Clin Exp Dermatol 31:89–93. doi:10.1111/j.1365-2230.2005.01980.x

    Article  PubMed  Google Scholar 

  2. Arkwright PD, Motala C, Subramanian H, Spergel J, Schneider LC, Wollenberg A, Atopic Dermatitis Working Group of the Allergic Skin Diseases Committee of the A (2013) Management of difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract 1:142–151. doi:10.1016/j.jaip.2012.09.002

    Article  PubMed  Google Scholar 

  3. Ashikaga T, Hoya M, Itagaki H, Katsumura Y, Aiba S (2002) Evaluation of CD86 expression and MHC class II molecule internalization in THP-1 human monocyte cells as predictive endpoints for contact sensitizers. Toxicol In Vitro 16:711–716

    Article  CAS  PubMed  Google Scholar 

  4. Auwerx J (1991) The human leukemia cell line, THP-1: a multifaceted model for the study of monocyte-macrophage differentiation. Experientia 47:22–31

    Article  CAS  PubMed  Google Scholar 

  5. Bieber T (2010) Atopic dermatitis. Ann Dermatol 22:125–137. doi:10.5021/ad.2010.22.2.125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bieber T, D’Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G, Schmid-Grendelmeier P (2017) Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 139:S58–S64. doi:10.1016/j.jaci.2017.01.008

    Article  PubMed  Google Scholar 

  7. Biedermann T, Skabytska Y, Kaesler S, Volz T (2015) Regulation of T cell immunity in atopic dermatitis by microbes: the Yin and Yang of cutaneous inflammation. Front Immunol 6:353. doi:10.3389/fimmu.2015.00353

    Article  PubMed  PubMed Central  Google Scholar 

  8. Boguniewicz M, Leung DY (2011) Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol Rev 242:233–246. doi:10.1111/j.1600-065X.2011.01027.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brunner PM, Guttman-Yassky E, Leung DY (2017) The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol 139:S65–S76. doi:10.1016/j.jaci.2017.01.011

    Article  CAS  PubMed  Google Scholar 

  10. Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, Amagai M, Luger TA, Deleuran M, Werfel T, Eyerich K, Stingl G, Councilors of the International Eczema C (2017) Increasing comorbidities suggest that atopic dermatitis is a systemic disorder. J Invest Dermatol 137:18–25. doi:10.1016/j.jid.2016.08.022

    Article  CAS  PubMed  Google Scholar 

  11. Chan LS, Robinson N, Xu L (2001) Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol 117:977–983. doi:10.1046/j.0022-202x.2001.01484.x

    Article  CAS  PubMed  Google Scholar 

  12. Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, El Ghalbzouri A, Bouwstra JA (2014) TNF-alpha and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol 134:1941–1950. doi:10.1038/jid.2014.83

    Article  CAS  PubMed  Google Scholar 

  13. de Vries IJ, Langeveld-Wildschut EG, van Reijsen FC, Dubois GR, van den Hoek JA, Bihari IC, van Wichen D, de Weger RA, Knol EF, Thepen T, Bruijnzeel-Koomen CA (1998) Adhesion molecule expression on skin endothelia in atopic dermatitis: effects of TNF-alpha and IL-4. J Allergy Clin Immunol 102:461–468

    Article  PubMed  Google Scholar 

  14. Feldman M, Santos J, Grenier D (2011) Comparative evaluation of two structurally related flavonoids, isoliquiritigenin and liquiritigenin, for their oral infection therapeutic potential. J Nat Prod 74:1862–1867. doi:10.1021/np200174h

    Article  CAS  PubMed  Google Scholar 

  15. Galli SJ, Tsai M, Piliponsky AM (2008) The development of allergic inflammation. Nature 454:445–454. doi:10.1038/nature07204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Heratizadeh A, Werfel T (2016) Anti-inflammatory therapies in atopic dermatitis. Allergy 71:1666–1675. doi:10.1111/all.13065

    Article  CAS  PubMed  Google Scholar 

  17. Kaminska B (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy–from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 1754:253–262. doi:10.1016/j.bbapap.2005.08.017

    Article  CAS  PubMed  Google Scholar 

  18. Kumar S, Sharma A, Madan B, Singhal V, Ghosh B (2007) Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells. Biochem Pharmacol 73:1602–1612. doi:10.1016/j.bcp.2007.01.015

    Article  CAS  PubMed  Google Scholar 

  19. Kwon HM, Choi YJ, Choi JS, Kang SW, Bae JY, Kang IJ, Jun JG, Lee SS, Lim SS, Kang YH (2007) Blockade of cytokine-induced endothelial cell adhesion molecule expression by licorice isoliquiritigenin through NF-kappaB signal disruption. Exp Biol Med (Maywood) 232:235–245

    CAS  Google Scholar 

  20. Leung DY, Bieber T (2003) Atopic dermatitis. Lancet 361:151–160. doi:10.1016/S0140-6736(03)12193-9

    Article  PubMed  Google Scholar 

  21. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657. doi:10.1172/JCI21060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu FT, Goodarzi H, Chen HY (2011) IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol 41:298–310. doi:10.1007/s12016-011-8252-4

    Article  CAS  PubMed  Google Scholar 

  23. Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, Ra C (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461–466

    Article  CAS  PubMed  Google Scholar 

  24. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173. doi:10.1146/annurev.iy.07.040189.001045

    Article  CAS  PubMed  Google Scholar 

  25. Novak N, Bieber T, Leung DY (2003) Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 112:S128–S139. doi:10.1016/j.jaci.2003.09.032

    Article  CAS  PubMed  Google Scholar 

  26. Peng F, Du Q, Peng C, Wang N, Tang H, Xie X, Shen J, Chen J (2015) A review: the pharmacology of Isoliquiritigenin. Phytother Res 29:969–977. doi:10.1002/ptr.5348

    Article  CAS  PubMed  Google Scholar 

  27. Roesner LM, Werfel T, Heratizadeh A (2016) The adaptive immune system in atopic dermatitis and implications on therapy. Expert Rev Clin Immunol 12:787–796. doi:10.1586/1744666X.2016.1165093

    Article  CAS  PubMed  Google Scholar 

  28. Sakaguchi H, Ashikaga T, Miyazawa M, Kosaka N, Ito Y, Yoneyama K, Sono S, Itagaki H, Toyoda H, Suzuki H (2009) The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitization test–human cell line activation test (h-CLAT). Cell Biol Toxicol 25:109–126. doi:10.1007/s10565-008-9059-9

    Article  CAS  PubMed  Google Scholar 

  29. Schmid-Grendelmeier P, Ballmer-Weber BK (2010) Atopic dermatitis—current insights into path physiology and management. Ther Umsch 67:175–185. doi:10.1024/0040-5930/a000031

    Article  PubMed  Google Scholar 

  30. Senra MS, Wollenberg A (2014) Psychodermatological aspects of atopic dermatitis. Br J Dermatol 170(Suppl 1):38–43. doi:10.1111/bjd.13084

    Article  CAS  PubMed  Google Scholar 

  31. Shaw TE, Currie GP, Koudelka CW, Simpson EL (2011) Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol 131:67–73. doi:10.1038/jid.2010.251

    Article  CAS  PubMed  Google Scholar 

  32. Toshitani A, Ansel JC, Chan SC, Li SH, Hanifin JM (1993) Increased interleukin 6 production by T cells derived from patients with atopic dermatitis. J Invest Dermatol 100:299–304

    Article  CAS  PubMed  Google Scholar 

  33. Traidl C, Jugert F, Krieg T, Merk H, Hunzelmann N (1999) Inhibition of allergic contact dermatitis to DNCB but not to oxazolone in interleukin-4-deficient mice. J Invest Dermatol 112:476–482. doi:10.1046/j.1523-1747.1999.00550.x

    Article  CAS  PubMed  Google Scholar 

  34. Weidinger S, Novak N (2016) Atopic dermatitis. Lancet 387:1109–1122. doi:10.1016/S0140-6736(15)00149-X

    Article  PubMed  Google Scholar 

  35. Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, Hoetzenecker W, Knol E, Simon HU, Wollenberg A, Bieber T, Lauener R, Schmid-Grendelmeier P, Traidl-Hoffmann C, Akdis CA (2016) Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 138:336–349. doi:10.1016/j.jaci.2016.06.010

    Article  CAS  PubMed  Google Scholar 

  36. Werfel T, Biedermann T (2015) Current novel approaches in systemic therapy of atopic dermatitis: specific inhibition of cutaneous Th2 polarized inflammation and itch. Curr Opin Allergy Clin Immunol 15:446–452. doi:10.1097/ACI.0000000000000199

    Article  CAS  PubMed  Google Scholar 

  37. Yang N, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, Goldfarb J, Sampson HA, Li XM (2013) Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI, inhibit memory Th2 responses in vitro and in vivo. Phytother Res 27:1381–1391. doi:10.1002/ptr.4862

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by Qingdao Postdoctoral Application Research Funded Project (2015162).

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Authors and Affiliations

  1. The Affiliated Qingdao Municipal Hospital of Qingdao University, No. 1 Jiaozhou Road, Qingdao, 266011, China

    Haiyang Yu, Yongxi Li & Min Li

  2. Qingdao Haici Medical Group, No. 4 Renmin Road, Qingdao, 266033, China

    Haiyan Li

  3. Qingdao University, No. 308 Ningxia Road, Qingdao, 266071, China

    Haiyan Li

  4. The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266001, China

    Guanzhi Chen

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  1. Haiyang Yu
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Correspondence to Guanzhi Chen.

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Yu, H., Li, H., Li, Y. et al. Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin lesions in mice. Arch Dermatol Res 309, 805–813 (2017). https://doi.org/10.1007/s00403-017-1787-3

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  • DOI: https://doi.org/10.1007/s00403-017-1787-3

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