Quercetin attenuates inflammation in rosacea by directly targeting p65 and ICAM-1

Life Sci. 2024 Jun 15:347:122675. doi: 10.1016/j.lfs.2024.122675. Epub 2024 Apr 28.

Abstract

Aims: Rosacea is an inflammatory skin disease with immune and vascular dysfunction. Although there are multiple treatment strategies for rosacea, the clinical outcomes are unsatisfactory.

Main methods: Combining transcriptome data and the Connectivity Map database quercetin was identified as a novel candidate for rosacea. Next, the therapeutic efficacy of quercetin was substantiated through proteomic analyses, in vivo experiments, and in vitro assays. Additionally, the utilization of DARTS, molecular docking and experimental verification revealed the therapeutic mechanisms of quercetin.

Key findings: Treatment with quercetin resulted in the following effects: (i) it effectively ameliorated rosacea-like features by reducing immune infiltration and angiogenesis; (ii) it suppressed the expression of inflammatory mediators in HaCaT cells and HDMECs; (iii) it interacted with p65 and ICAM-1 directly, and this interaction resulted in the repression of NF-κB signal and ICAM-1 expression in rosacea.

Significance: We show for the first time that quercetin interacted with p65 and ICAM-1 directly to alleviated inflammatory and vascular dysfunction, suggesting quercetin is a novel, promising therapeutic candidate for rosacea.

Keywords: Angiogenesis; Immune infiltration; Quercetin; rosacea.

MeSH terms

  • Animals
  • Female
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Intercellular Adhesion Molecule-1* / metabolism
  • Male
  • Mice
  • Molecular Docking Simulation
  • Quercetin* / pharmacology
  • Rosacea* / drug therapy
  • Rosacea* / metabolism
  • Transcription Factor RelA* / metabolism

Substances

  • Quercetin
  • Intercellular Adhesion Molecule-1
  • Transcription Factor RelA
  • ICAM1 protein, human
  • RELA protein, human