Chlorogenic Acid Activates CFTR-Mediated Cl– Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis. (August 2015)

• Record Type: Journal Article
• Authors: Illing, Elisa A.; Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel F.; Dunlap, Quinn A.; Sorscher, Eric J.; Woodworth, Bradford A.
• Is Part Of: Otolaryngology--head and neck surgery. Volume 153:Number 2(2015:Aug.)
• Page Start: 291
• Page End: 297
• Publication Date: 2015-08
• Subjects: transepithelial ion transport -- chlorogenic acid -- CFTR -- chronic sinusitis -- chloride secretion -- murine nasal culture -- sinus epithelium -- mucociliary clearance; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599815586720
• Languages: English
• ISSNs: 0194-5998

Abstract

Objectives: 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. Study Design: Basic research. Setting: Laboratory. Subjects and 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. Conclusion: 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.