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

Arch Dermatol Res. 2017 Dec;309(10):805-813. doi: 10.1007/s00403-017-1787-3. Epub 2017 Oct 12.

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.

Keywords: Atopic dermatitis; DNCB; Isoliquiritigenin; THP-1; Th2 cells.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • B7-2 Antigen / metabolism
  • Cell Line
  • Chalcones / pharmacology
  • Chalcones / therapeutic use*
  • Cytokines / metabolism
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / pathology
  • Dinitrochlorobenzene / toxicity
  • Disease Models, Animal
  • Female
  • Glycyrrhiza / chemistry*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Monocytes
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Th2 Cells / drug effects*
  • Th2 Cells / metabolism
  • Up-Regulation

Substances

  • B7-2 Antigen
  • CD86 protein, human
  • Chalcones
  • Cytokines
  • Dinitrochlorobenzene
  • ICAM1 protein, human
  • Intercellular Adhesion Molecule-1
  • isoliquiritigenin