PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation

Int J Mol Sci. 2020 Feb 12;21(4):1215. doi: 10.3390/ijms21041215.


Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/β-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a "dual mode" of action: NF-κB inhibition and Wnt/β-catenin stimulation.

Keywords: NF-κB; Wnt/β-catenin pathway; adenosine A2A receptor; psoriasis.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Disease Models, Animal
  • Imiquimod / adverse effects*
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Polydeoxyribonucleotides / pharmacology*
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism*
  • Psoriasis / pathology
  • Receptor, Adenosine A2A / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism


  • Cytokines
  • NF-kappa B
  • Polydeoxyribonucleotides
  • Receptor, Adenosine A2A
  • beta Catenin
  • Imiquimod