Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells

Cell Physiol Biochem. 2017;44(3):1146-1160. doi: 10.1159/000485419. Epub 2017 Nov 27.

Abstract

Background/aims: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin.

Methods: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR.

Results: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression.

Conclusion: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.

Keywords: Airway epithelium; CFTR; Cl- secretion; Naringenin; Traditional Chinese medicine.

MeSH terms

  • Animals
  • Barium Compounds / pharmacology
  • Benzoates / pharmacology
  • Cells, Cultured
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / metabolism
  • Chlorides / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / analysis
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Female
  • Flavanones / pharmacology*
  • Humans
  • Imines / pharmacology
  • Ion Transport / drug effects
  • Male
  • Microscopy, Fluorescence
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Thiazolidines / pharmacology
  • Trachea / cytology
  • ortho-Aminobenzoates / pharmacology

Substances

  • 3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone
  • Barium Compounds
  • Benzoates
  • Chloride Channels
  • Chlorides
  • Flavanones
  • Imines
  • Thiazolidines
  • ortho-Aminobenzoates
  • barium chloride
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin
  • RMI 12330A
  • fenamic acid
  • Cyclic AMP
  • naringenin