Anti-Inflammatory Effects of Ellagic Acid on Keratinocytes via MAPK and STAT Pathways

Int J Mol Sci. 2021 Jan 28;22(3):1277. doi: 10.3390/ijms22031277.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by an impaired skin barrier and intense itchiness, which decreases the individual's quality of life. No fully effective therapeutic agents have prevailed for AD due to an insufficient grasp of the complex etiology. Ellagic acid (EA), a natural compound, has anti-inflammatory properties in chronic diseases. The effects of EA on AD have not yet been explored. The present study investigated the effects of EA on TNF-α/IFN-γ-stimulated HaCaT keratinocytes and house dust mite-induced AD-like skin lesions in NC/Nga mice. Treatment with EA suppressed inflammatory responses in keratinocytes by regulating critical inflammatory signaling pathways, such as mitogen-activated protein kinases and signal transducers and activators of transcription. In vivo studies using a DfE-induced AD mouse model showed the effects of EA administration through ameliorated skin lesions via decremented histological inflammatory reactions. These results suggest that EA could be a potential therapeutic alternative for the treatment of AD by inhibiting inflammatory signaling pathways.

Keywords: MAPKs; STATs; atopic dermatitis; chronic disease; ellagic acid; inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigens, Dermatophagoides / administration & dosage
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / immunology
  • Chemokine CCL22 / genetics
  • Chemokine CCL22 / immunology
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / immunology
  • Complex Mixtures / administration & dosage
  • Cytokines / genetics
  • Cytokines / immunology
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / genetics
  • Dermatitis, Atopic / immunology
  • Dermatophagoides farinae / chemistry*
  • Dermatophagoides farinae / immunology
  • Disease Models, Animal
  • Ellagic Acid / pharmacology*
  • Female
  • Gene Expression Regulation
  • HaCaT Cells
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinases / genetics*
  • Mitogen-Activated Protein Kinases / immunology
  • STAT1 Transcription Factor / genetics*
  • STAT1 Transcription Factor / immunology
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / immunology
  • Signal Transduction
  • Thymic Stromal Lymphopoietin
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antigens, Dermatophagoides
  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Ccl5 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokine CCL5
  • Complex Mixtures
  • Cytokines
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Ellagic Acid
  • Interferon-gamma
  • Mitogen-Activated Protein Kinases
  • Thymic Stromal Lymphopoietin