Anti-Atopic Effect of Isatidis Folium Water Extract in TNF-α/IFN-γ-Induced HaCaT Cells and DNCB-Induced Atopic Dermatitis Mouse Model

Molecules. 2023 May 8;28(9):3960. doi: 10.3390/molecules28093960.

Abstract

Isatidis folium or Isatis tinctoria L. is a flowering plant of the Brassicaceae family, commonly known as woad, with an ancient and well-documented history as an indigo dye and medicinal plant. This study aimed to evaluate the anti-atopic dermatitis (AD) effects of Isatidis folium water extract (WIF) using a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model and to investigate the underlying mechanism using tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated HaCaT cells. Oral administration of WIF reduced spleen weight, decreased serum IgE and TNF-α levels, reduced epidermal and dermal thickness, and inhibited eosinophil and mast cell recruitment to the dermis compared to DNCB-induced control groups. Furthermore, oral WIF administration suppressed extracellular signal-regulated kinase and p38 mitogen-activated protein kinase protein expression levels, p65 translocation from the cytoplasm to the nucleus, and mRNA expression of TNF-α, IFN-γ, interleukin (IL)-6, and IL-13 in skin lesion tissues. In HaCaT cells, WIF suppressed the production of regulated upon activation, normal T cell expressed and secreted (RANTES), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), MCP-1, and MIP-3a, which are inflammatory cytokines and chemokines related to AD, and inhibited the mRNA expression of RANTES, TARC, and MDC in TNF-α/IFN-γ-stimulated HaCaT cells. Overall, the results revealed that WIF ameliorated AD-like skin inflammation by suppressing proinflammatory cytokine and chemokine production via nuclear factor-κB pathway inhibition, suggesting WIF as a potential candidate for AD treatment.

Keywords: Isatidis folium; Isatis tinctoria L.; anti-inflammation; atopic dermatitis; keratinocytes.

MeSH terms

  • Animals
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / drug therapy
  • Dermatitis, Atopic* / metabolism
  • Dinitrochlorobenzene / adverse effects
  • Dinitrochlorobenzene / metabolism
  • HaCaT Cells
  • Humans
  • Interferon-gamma / metabolism
  • Keratinocytes
  • Mice
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • Tumor Necrosis Factor-alpha* / metabolism
  • Water / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Dinitrochlorobenzene
  • Interferon-gamma
  • Water
  • Cytokines
  • NF-kappa B
  • Chemokines
  • RNA, Messenger