title: The bioflavonoid compound, sinupret, stimulates transepithelial chloride transport in vitro and in vivo.
abstract: OBJECTIVE
  Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance in sinonasal epithelium leading to chronic rhinosinusitis. Abnormal chloride (Cl(-)) transport is one mechanism that contributes to this disorder, as demonstrated by the disease cystic fibrosis. Identifying safe compounds that stimulate transepithelial Cl(-) transport is critical to improving hydration of the ASL and promoting mucociliary transport. Sinupret (Bionorica, LLC, San Clemente, CA), a combination of naturally occurring bioflavonoids, is a widely used treatment for respiratory ailments in Europe. However, the effects of Sinupret on target respiratory epithelium have yet to be fully investigated. The present study evaluated the mechanisms underlying this bioflavonoid therapeutic on transepithelial Cl(-) transport in respiratory epithelium.
  
  
  METHODS
  In vitro and in vivo investigation.
  
  
  METHODS
  Well characterized murine nasal septal epithelial (MNSE) cultures, and murine nasal potential difference (NPD) techniques were used to evaluate the effects of Sinupret on Cl(-) secretion.
  
  
  RESULTS
  The change in Sinupret-stimulated current (Delta I(SC) expressed as microA/cm(2)) in MNSE, representing Cl(-) secretion, was significantly increased when compared to controls (19.04 + or - 1.67 microA/cm(2) vs. 1.8 + or - 0.35 microA/cm(2), respectively; P = .00005). Transepithelial Cl(-) transport measured in the murine NPD in vivo assay (n = 42) was also significantly enhanced when compared to controls (-0.8 mV vs. -0.9 mV; P = .0004). Importantly, Sinupret-stimulated Cl(-) transport was substantially more robust in vivo than forskolin, a compound among the strongest known cystic fibrosis transmembrane conductance regulator activators (-3.8 mV vs. -1.65 mV; P = .01).
  
  
  CONCLUSIONS
  Sinupret strongly activates transepithelial Cl(-) secretion through a mechanism known to hydrate the ASL of respiratory epithelium. This is one means by which the medication is likely to exert therapeutic benefit.
authors.affiliation: Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Virgin
authors.forename: Shaoyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Schuster
authors.forename: Christopher
authors.initials: C
authors.lastname: Azbell
authors.forename: James
authors.initials: J
authors.lastname: Fortenberry
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sorscher
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Woodworth
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D005419:Flavonoids; D010936:Plant Extracts; D005576:Colforsin; C028353:Sinupret