Chlorogenic Acid: A Potential Activator of Dysfunctional Mucus Transport in Chronic Rhinosinusits

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.