Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory cytokine production, and aquaporin 5 downregulation through suppressing the NF-κB pathway in human nasal epithelial cells

Chem Biol Interact. 2018 Apr 1:285:21-26. doi: 10.1016/j.cbi.2018.02.010. Epub 2018 Feb 13.

Abstract

Allergic rhinitis (AR) is a chronic respiratory inflammatory disease. Glycyrrhizin is a main bioactive component of the licorice root extract and exhibits anti-inflammatory activity. However, the role of glycyrrhizin in AR has not been studied. The aim of the present study was to investigate the effect of glycyrrhizin on histamine-induced human nasal epithelial cells (HNEpCs). Here, we found that glycyrrhizin (20 or 40 μM) inhibited histamine-induced the mRNA expression and secretion of mucin 5 subtype AC (MUC5AC), interleukin (IL)-6 and IL-8 in HNEpCs. The expression levels of aquaporin 5 (AQP5) and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (p-CREB) were decreased by histamine in HNEpCs and increased in cells treated with glycyrrhizin. The glycyrrhizin treatment inhibited histamine-induced expressions of p-NF-κB p65 and p-IκBα in HNEpCs, indicating that glycyrrhizin inhibited the activation of NF-κB pathway in histamine-induced HNEpCs. In addition, inhibition of the NF-κB pathway exhibited the similar effect with glycyrrhizin on histamine-induced HNEpCs. In summary, the results showed that glycyrrhizin reversed the effect of histamine on MUC5AC expression, inflammatory cytokine production, and AQP5 expression in HNEpCs, and the NF-κB pathway was involved in the effect. Glycyrrhizin might be used for complementary and alternative therapeutics of AR.

Keywords: Allergic rhinitis; Glycyrrhizin; Inflammation; MUC5AC; NF-κB pathway.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Aquaporin 5 / drug effects*
  • Aquaporin 5 / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / metabolism*
  • Gene Expression Regulation / drug effects*
  • Glycyrrhizic Acid / pharmacology*
  • Histamine / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Mucin 5AC / genetics*
  • NF-kappaB-Inducing Kinase
  • Nasal Mucosa / drug effects*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Aquaporin 5
  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Mucin 5AC
  • Glycyrrhizic Acid
  • Histamine
  • Protein Serine-Threonine Kinases