Diosmetin ameliorates psoriasis-associated inflammation and keratinocyte hyperproliferation by modulation of PGC-1α / YAP signaling pathway

Int Immunopharmacol. 2024 Jun 15:134:112248. doi: 10.1016/j.intimp.2024.112248. Epub 2024 May 14.

Abstract

Psoriasis, characterized by aberrant epidermal keratinocyte proliferation and differentiation, is a chronic inflammatory immune-related skin disease. Diosmetin (Dios), derived from citrus fruits, exhibits anti-inflammatory and anti-proliferative properties. In this study, IL-17A-induced HaCaT cell model and Imiquimod (IMQ)-induced mouse model were utilized to investigate the effects of Dios against psoriasis. The morphology and biomarkers of psoriasis were regarded as the preliminary evaluation including PASI score, skin thickness, H&E staining, EdU staining and inflammatory factors. Transcriptomics analysis revealed PGC-1α as a key target for Dios in ameliorating psoriasis. Specifically, Dios, through PGC-1α, suppressed YAP-mediated proliferation and inflammatory responses in psoriatic keratinocytes. In conclusion, Dios shows promise in psoriasis treatment and holds potential for development as targeted medications for application in psoriasis.

Keywords: Diosmetin (Dios); Inflammation; Proliferation; Proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α); Psoriasis; Yes-associated protein (YAP).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cell Line
  • Cell Proliferation* / drug effects
  • Disease Models, Animal
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • HaCaT Cells
  • Humans
  • Imiquimod*
  • Inflammation / drug therapy
  • Interleukin-17 / metabolism
  • Keratinocytes* / drug effects
  • Keratinocytes* / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha* / metabolism
  • Psoriasis* / drug therapy
  • Psoriasis* / immunology
  • Signal Transduction* / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins / metabolism

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • diosmetin
  • Imiquimod
  • Flavonoids
  • Anti-Inflammatory Agents
  • YAP-Signaling Proteins
  • Transcription Factors
  • PPARGC1A protein, human
  • Interleukin-17
  • YAP1 protein, human
  • Yap1 protein, mouse