Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse

J Pharmacol Sci. 2015 Jul;128(3):116-24. doi: 10.1016/j.jphs.2015.05.008. Epub 2015 Jun 9.

Abstract

Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has been reported to possess anti-inflammatory and anti-angiogenic activaties. In this study, our aim was to investigate anti-psoriatic activities of HK and the involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and TNF-α-induced NF-κB (p65) activation were analyzed by respective FCS and immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2 cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65 activation, as well as other angiogenic and inflammatory parameters were studied by immunostainings. Importantly, we found that HK significantly decreased the ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-α-induced activation of NF-κB. The morphology and histological features of psoriasis were effectively improved by HK treatment. The expression of TNF-α and IFN-γ, and their corresponding mRNA levels were down-regulated and the expression of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p-ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our study suggested that HK exhibits anti-psoriatic effects through the inhibition of NF-κB and VEGFR-2.

Keywords: Honokiol; K14-VEGF; NF-κB; Psoriasis; VEGFR-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Anti-Inflammatory Agents
  • Biphenyl Compounds / isolation & purification
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use*
  • CD4-Positive T-Lymphocytes
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Lignans / therapeutic use*
  • Magnolia
  • Mice, Transgenic
  • Molecular Targeted Therapy*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Phytotherapy*
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Psoriasis / pathology
  • Th1-Th2 Balance / drug effects
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents
  • Biphenyl Compounds
  • Lignans
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • honokiol
  • Vascular Endothelial Growth Factor Receptor-2