Propolis suppresses atopic dermatitis through targeting the MKK4 pathway

Biofactors. 2025 Jan-Feb;51(1):e2119. doi: 10.1002/biof.2119. Epub 2024 Aug 20.

Abstract

Propolis is a natural resinous substance made by bees through mixing various plant sources. Propolis has been widely recognized as a functional food due to its diverse range of beneficial bioactivities. However, the therapeutic effects of consuming propolis against atopic dermatitis (AD) remain largely unknown. The current study aimed to investigate the potential efficacy of propolis against AD and explore the active compound as well as the direct molecular target. In HaCaT keratinocytes, propolis inhibited TNF-α-induced interleukin (IL)-6 and IL-8 secretion. It also led to a reduction in chemokines such as monocyte chemoattractant protein-1 (MCP-1) and macrophage-derived chemokine (MDC), while restoring the levels of barrier proteins, filaggrin and involucrin. Propolis exhibited similar effects in AD-like human skin, leading to the suppression of AD markers and the restoration of barrier proteins. In DNCB-induced mice, oral administration of propolis attenuated AD symptoms, improved barrier function, and reduced scratching frequency and transepidermal water loss (TEWL). In addition, propolis reversed the mRNA levels of AD-related markers in mouse dorsal skin. These effects were attributed to caffeic acid phenethyl ester (CAPE), the active compound identified by comparing major components of propolis. Mechanistic studies revealed that CAPE as well as propolis could directly and selectively target MKK4. Collectively, these findings demonstrate that propolis may be used as a functional food agent for the treatment of AD.

Keywords: MKK4; atopic dermatitis; caffeic acid phenethyl ester; propolis; skin barrier.

MeSH terms

  • Animals
  • Caffeic Acids* / pharmacology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / drug therapy
  • Dermatitis, Atopic* / metabolism
  • Dermatitis, Atopic* / pathology
  • Dinitrochlorobenzene
  • Disease Models, Animal
  • Filaggrin Proteins*
  • HaCaT Cells
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Keratinocytes* / drug effects
  • Keratinocytes* / metabolism
  • MAP Kinase Kinase 4* / genetics
  • MAP Kinase Kinase 4* / metabolism
  • Male
  • Mice
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / pharmacology
  • Propolis* / pharmacology
  • Protein Precursors
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Propolis
  • Filaggrin Proteins
  • FLG protein, human
  • MAP Kinase Kinase 4
  • Caffeic Acids
  • caffeic acid phenethyl ester
  • Interleukin-6
  • Phenylethyl Alcohol
  • Tumor Necrosis Factor-alpha
  • MAP2K4 protein, human
  • Interleukin-8
  • Dinitrochlorobenzene
  • involucrin
  • Chemokine CCL2
  • Intermediate Filament Proteins
  • Protein Precursors