Withanolides, Extracted from Datura Metel L. Inhibit Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis via the STAT3/P38/ERK1/2 Pathway

Molecules. 2019 Jul 17;24(14):2596. doi: 10.3390/molecules24142596.

Abstract

Psoriasis is an immune-mediated inflammatory dermatosis characterized by epidermal hyperplasia and excessive infiltration of inflammatory cells. Withanolides, extracted from Datura metel L.; are the main effective components for the treatment of psoriasis. However, the precise mechanisms of action of withanolides for the treatment of psoriasis remain unclear. We found that treatment with withanolides alleviated imiquimod (IMQ)-induced epidermal hyperplasia and inflammatory cell infiltration in the effective skin of model mice. In addition, we also found that withanolides suppressed the activation of STAT3, ERK1/2 and P38 signaling pathways in IMQ-stimulated HaCat cells. These results suggest that withanolides possess an anti-inflammatory effect and have significant therapeutic potential for the prevention and treatment of psoriasis.

Keywords: Datura metel L.; imiquimod; inflammation; psoriasis; withanolides.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Datura metel / chemistry*
  • Dermatitis / drug therapy*
  • Dermatitis / genetics
  • Dermatitis / pathology
  • Humans
  • Imiquimod / toxicity
  • Keratinocytes / drug effects
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • Mice
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / genetics
  • Psoriasis / pathology
  • STAT3 Transcription Factor / genetics
  • Withanolides / chemistry
  • Withanolides / pharmacology*

Substances

  • STAT3 Transcription Factor
  • Withanolides
  • Imiquimod