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