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01-12-2017 | Original Paper

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

Authors: Haiyang Yu, Haiyan Li, Yongxi Li, Min Li, Guanzhi Chen

Published in: Archives of Dermatological Research | Issue 10/2017

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.

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 CrossRefPubMed

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 CrossRefPubMed

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 16:711–716CrossRefPubMed

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

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

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 CrossRefPubMed

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 102:461–468CrossRefPubMed

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 CrossRefPubMed

15.

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

16.

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

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 CrossRefPubMed

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 CrossRefPubMed

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

20.

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

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 CrossRefPubMedPubMedCentral

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 CrossRefPubMed

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 9:461–466CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

30.

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

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 CrossRefPubMed

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 100:299–304CrossRefPubMed

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 CrossRefPubMed

34.

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

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 CrossRefPubMed

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 CrossRefPubMed

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 CrossRefPubMed

Title: Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin lesions in mice
Authors: Haiyang Yu
Haiyan Li
Yongxi Li
Min Li
Guanzhi Chen
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Archives of Dermatological Research / Issue 10/2017
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-017-1787-3

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

Abstract

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