Bakuchicin attenuates atopic skin inflammation

Biomed Pharmacother. 2020 Sep:129:110466. doi: 10.1016/j.biopha.2020.110466. Epub 2020 Jul 1.

Abstract

Psoralea corylifolia is a medicinal herb that provides advantageous pharmacological effects against vitiligo and skin rash. Former studies have shown that bakuchicin, a furanocoumarin compound from the fruits of P. corylifolia, has therapeutic effects against inflammation, and infection. This study aimed to define the pharmacological effects of bakuchicin on inflammatory responses and lichenification, the major symptoms of atopic dermatitis (AD). To induce AD-like skin inflammation, we exposed the ears of female BALB/c mice to 2, 4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae (house dust mite) extract (DFE) for 4 weeks. Intragastric administration of bakuchicin attenuated the symptoms of AD-like skin inflammation, as evident by reductions in ear thickness, erythema, and keratosis. Bakuchicin also reversed increases in auricular epidermal and dermal layer thicknesses, and attenuated eosinophil and mast cell infiltration in AD-induced mice. It also suppressed Th2 gene expression as well as that of pro-inflammatory cytokines and chemokines, such as interleukin (IL)-4, IL-13, IL-31, IL-1β, IL-6, CXCL-1, and CCL-17 in the ear tissue. The levels of total and DFE-specific immunoglobulin (Ig)E, and IgG2a in the mice sera were reduced by the bakuchicin. To investigate the effect of bakuchicin on keratinocytes, experiments were performed using HaCaT cells, the representative cell type used in skin disease studies. Tumor necrosis factor-α and interferon-γ were used to activate keratinocytes. Bakuchicin suppressed Th2 gene expression and that of pro-inflammatory cytokines and chemokines; it also suppressed STAT-1 phosphorylation and the nuclear translocation of NF-κB in activated keratinocytes. These results suggest that bakuchicin attenuated AD symptoms, thus suggesting it as a potential therapeutic agent for the treatment of AD.

Keywords: Atopic dermatitis; Bakuchicin; Eosinophils; Keratinocytes.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cell Line
  • Chronic Disease
  • Cytokines / metabolism
  • Dermatitis, Atopic / chemically induced
  • Dermatitis, Atopic / metabolism
  • Dermatitis, Atopic / pathology
  • Dermatitis, Atopic / prevention & control*
  • Dermatologic Agents / pharmacology*
  • Dinitrochlorobenzene
  • Disease Models, Animal
  • Female
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Phosphorylation
  • STAT1 Transcription Factor / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology

Substances

  • Anti-Inflammatory Agents
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Dermatologic Agents
  • Dinitrochlorobenzene
  • Heterocyclic Compounds, 3-Ring
  • Immunoglobulin G
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • bakuchicin
  • Immunoglobulin E