Effect of cinnamamides on atopic dermatitis through regulation of IL-4 in CD4+ cells

J Enzyme Inhib Med Chem. 2019 Dec;34(1):613-619. doi: 10.1080/14756366.2019.1569647.

Abstract

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Keywords: Atopic dermatitis; CD4+ T cells; IL-4; Th1/Th2 cytokines; cinnamamides.

MeSH terms

  • Administration, Oral
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / drug effects
  • Cinnamates / administration & dosage
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Dermatitis, Atopic / drug therapy*
  • Dose-Response Relationship, Drug
  • Immunoglobulins / biosynthesis
  • Interleukin-4 / antagonists & inhibitors*
  • Interleukin-4 / metabolism
  • Lymph Nodes / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Organ Size / drug effects
  • Structure-Activity Relationship

Substances

  • Cinnamates
  • IL4 protein, human
  • Immunoglobulins
  • Interleukin-4
  • cinnamamide

Grants and funding

This work was supported by the KRIBB Research Initiative Program, and the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea [grant number NRF-2017S1A5A8019407].