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Topical application of an amygdalin analogue reduces inflammation and keratinocyte proliferation in a psoriasis mouse model.

Authors
  • Gago-López, Nuria1, 2
  • Lagunas Arnal, Carmen3
  • Perez, Juan J4
  • Wagner, Erwin F5
  • 1 Genes, Development and Disease group, Cancer Cell Biology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO, Madrid, Spain. , (Spain)
  • 2 Melanoma group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO, Madrid, Spain. , (Spain)
  • 3 Ferrer Advanced Biotherapeutics, Grupo Ferrer Internacional S.A, Barcelona, Spain. , (Spain)
  • 4 Department of Chemical Engineering, Universitat Politecnica de Catalunya, Barcelona, Spain. , (Spain)
  • 5 Department of Dermatology and Department of Laboratory Medicine, Medical University of Vienna (MUW, Vienna, Austria. , (Austria)
Type
Published Article
Journal
Experimental Dermatology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Nov 01, 2021
Volume
30
Issue
11
Pages
1662–1674
Identifiers
DOI: 10.1111/exd.14390
PMID: 33998705
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Psoriasis is a chronic inflammatory skin disease without cure. Systemic and biological therapies are the most effective treatments for patients with severe psoriasis. However, these drugs can cause serious side effects from extended use. Safe and effective topical drugs are needed to decrease psoriatic plaques and reduce the risk of adverse effects. Amygdalin analogues are stable small molecules that showed benefits in psoriasis xenografts to immune-deficient mice by systemic application. However, whether topical application of these amygdalin analogues could reduce the progression of the psoriatic phenotype in an immune-competent organism is unknown. Here, we analyse the efficiency of topical application of an amygdalin analogue cream on a well-established genetic and immune-competent mouse model of psoriasis. Topical application of an amygdalin analogue cream ameliorates psoriasis-like disease in mice, reduces epidermal hyperplasia and skin inflammation. Amygdalin analogue treatment leads to reduced expression of local pro-inflammatory cytokines, but systemic pro-inflammatory cytokines that are highly expressed in psoriasis patients such as IL-17A, IL6 or G-CSF are also decreased. Furthermore, expression of important mediators of psoriasis initiation and epidermal hyperplasia, such as TNFa, S100A9 and TSLP, is decreased in lesional epidermis after amygdalin analogue treatment. In conclusion, we show that amygdalin analogue reduces the proliferative capacity of psoriasis-like stimulated keratinocytes and their inflammatory response in vivo and in vitro. These results suggest that topical application of amygdalin analogues may represent a safe and effective treatment for psoriasis. © 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.

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