title: Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.
abstract: OBJECTIVE
  Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water. The objective of this study is to evaluate the Cl(-) secretory capability of chlorogenic acid and its potential as a therapeutic activator of mucus clearance in sinus disease.
  
  
  METHODS
  Basic research.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Chlorogenic acid was tested on primary murine nasal septal epithelial (MNSE) (CFTR(+/+) and transgenic CFTR(-/-)) and human sinonasal epithelial (HSNE) (CFTR(+/+) and F508del/F508del) cultures under pharmacologic conditions in Ussing chambers to evaluate effects on transepithelial Cl(-) transport. Cellular cyclic adenosine monophosphate (cAMP), phosphorylation of the CFTR regulatory domain (R-D), and CFTR mRNA transcription were also measured.
  
  
  RESULTS
  Chlorogenic acid stimulated transepithelial Cl(-) secretion (change in short-circuit current [ΔISC = µA/cm(2)]) in MNSE (13.1 ± 0.9 vs 0.1 ± 0.1; P < .05) and HSNE (34.3 ± 0.9 vs 0.0 ± 0.1; P < .05). The drug had a long duration until peak effect at 15 to 30 minutes after application. Significant inhibition with INH-172 as well as absent stimulation in cultures lacking functional CFTR suggest effects are dependent on CFTR-mediated pathways. However, the absence of elevated cellular cAMP and phosphorylation the CFTR R-D indicates chlorogenic acid does not work through a PKA-dependent mechanism.
  
  
  CONCLUSIONS
  Chlorogenic acid is a water-soluble agent that promotes CFTR-mediated Cl(-) transport in mouse and human sinonasal epithelium. Translating activators of mucociliary transport to clinical use provides a new therapeutic approach to sinus disease. Further in vivo evaluation is planned.
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Illing
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Cho
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Skinner
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Quinn A
authors.initials: QA
authors.lastname: Dunlap
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama, USA bwoodwo@hotmail.com.
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Woodworth
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism*; D002726:Chlorogenic Acid / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009079:Mucociliary Clearance; D009297:Nasal Mucosa / Q000187:drug effects; D009300:Nasal Septum / Q000187:drug effects; D010254:Paranasal Sinus Diseases / Q000188:drug therapy; D012852:Sinusitis / Q000188:drug therapy*; D046509:Tissue Culture Techniques
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D002726:Chlorogenic Acid; D002713:Chlorine
keywords: CFTR; chloride secretion; chlorogenic acid; chronic sinusitis; mucociliary clearance; murine nasal culture; sinus epithelium; transepithelial ion transport