Chlorogenic Acid: A Potential Activator of Dysfunctional Mucus Transport in Chronic Rhinosinusits. (2nd September 2014)

• Record Type: Journal Article
• Authors: Illing, Elisa A.; Dean, Nichole; Dunlap, Quinn; Skinner, Daniel; Zhang, Shaoyan; Woodworth, Bradford A.
• Is Part Of: Otolaryngology--head and neck surgery. Volume 151(2014)Supplement 1
• Page Start: P113
• Page End: P114
• Publication Date: 2014-09-02
• Subjects: Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599814541627a264
• Languages: English
• ISSNs: 0194-5998

Abstract

Abstract : Objectives: Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid (CA). CA has a molecular structure similar to bioflavanoid polyphenols known to activate transepithelial Cl‐ transport in sinonasal epithelia. In contrast to bioflavonoids, chlorogenic acid is freely soluble in water. The objectives of this study are to evaluate the Cl‐ secretory capability of CA and potential as a therapeutic activator of mucus clearance in sinus disease. Methods: CA 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. Changes in airway surface liquid depth and CFTR mRNA transcription were also measured. Results: CA stimulated transepithelial Cl‐ secretion [(change in short‐circuit current(^†ISC)] in MNSE (13.11 ± 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 slow onset with peak effect at 15 minutes after application. Administration of the CFTR blocker INH‐172 significantly reduced ISC (MNSE −16.4 ± 1.0 vs −9 ± 0.9 and HSNE (−44.6 ± 1.0 vs 34.1 ± 0.3, P <. 05), indicating effects of the drug are likely mediated through CFTR. CA‐mediated Cl‐ secretion was absent in CFTR‐/‐ MNSE and F508del/F508del HSNE, confirming CFTR dependency. A modest increase in ASL depth was noted with 1 hour incubation (9.4 vs 8.3 µm). The compound did not alter CFTR mRNA levels when analyzed by quantitative reverse transcription polymerase chain reaction. Conclusions: CA is a water‐soluble agent that promotes CFTR‐mediated Cl‐ transport in sinonasal epithelium. Further in vivo evaluation as a therapeutic activator of mucus clearance is planned.