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Otolaryngol Head Neck Surg. 2015 Aug;153(2):291-7. doi: 10.1177/0194599815586720. Epub 2015 May 27.

Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.

Author information

1
University of Alabama at Birmingham, Birmingham, Alabama, USA.
2
University of Alabama at Birmingham, Birmingham, Alabama, USA bwoodwo@hotmail.com.

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.

KEYWORDS:

CFTR; chloride secretion; chlorogenic acid; chronic sinusitis; mucociliary clearance; murine nasal culture; sinus epithelium; transepithelial ion transport

PMID:
26019132
PMCID:
PMC4881747
DOI:
10.1177/0194599815586720
[Indexed for MEDLINE]
Free PMC Article

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