Quercetin Directly Targets JAK2 and PKCδ and Prevents UV-Induced Photoaging in Human Skin

Int J Mol Sci. 2019 Oct 23;20(21):5262. doi: 10.3390/ijms20215262.


Quercetin is a naturally occurring polyphenol present in various fruits and vegetables. The bioactive properties of quercetin include anti-oxidative, anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the effect of quercetin on skin aging and the direct molecular targets responsible have remained largely unknown. Herein, we investigated the protective effect of quercetin against UV-mediated skin aging and the molecular mechanisms responsible. Treatment with quercetin suppressed UV-induced matrix metalloproteinase-1 (MMP-1) and cyclooxygenase-2 (COX-2) expression and prevented UV-mediated collagen degradation in human skin tissues. Quercetin exerted potent inhibitory effects towards UV-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activity. Further examination of the upstream signaling pathways revealed that quercetin can attenuate UV-mediated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N terminal kinases (JNK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Kinase assays using purified protein demonstrated that quercetin can directly inhibit protein kinase C delta (PKCδ) and Janus kinase 2 (JAK2) kinase activity. Quercetin was observed to bind to PKCδ and JAK2 in pull-down assays. These findings suggest that quercetin can directly target PKCδ and JAK2 in the skin to elicit protective effects against UV-mediated skin aging and inflammation. Our results highlight the potential use of quercetin as a natural agent for anti-skin aging applications.

Keywords: JAK2; PKC-delta; quercetin; skin aging.

MeSH terms

  • Antioxidants / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Janus Kinase 2 / metabolism*
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 1 / metabolism
  • NF-kappa B / metabolism
  • Protein Kinase C-delta / metabolism*
  • Quercetin / pharmacology*
  • STAT3 Transcription Factor / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / radiation effects
  • Skin Aging*
  • Transcription Factor AP-1 / metabolism
  • Ultraviolet Rays / adverse effects


  • Antioxidants
  • NF-kappa B
  • STAT3 Transcription Factor
  • Transcription Factor AP-1
  • Quercetin
  • Cyclooxygenase 2
  • JAK2 protein, human
  • Janus Kinase 2
  • Protein Kinase C-delta
  • MMP1 protein, human
  • Matrix Metalloproteinase 1