Get access

The bioflavonoid compound, sinupret, stimulates transepithelial chloride transport in vitro and in vivo§

Authors

  • Frank Virgin MD,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • Shaoyan Zhang PhD,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    2. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • Daniel Schuster BS,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • Christopher Azbell BS,

    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • James Fortenberry BS,

    1. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • Eric J. Sorscher MD,

    1. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    2. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    Search for more papers by this author
  • Bradford A. Woodworth MD

    Corresponding author
    1. Department of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    2. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.
    • Otolaryngology–Head and Neck Surgery, University of Alabama at Birmingham, BDB 563; 1530 3rd Ave. S, Birmingham, AL 35294
    Search for more papers by this author

  • Presented at the Triological Society Southern Section Meeting, Orlando, Florida, U.S.A., February 4–7, 2010.

  • This research was funded by the American Rhinologic Society New Investigator Award (2009) and Flight Attendant's Medical Research Institute Young Clinical Scientist Award (072218) to Bradford A. Woodworth.

  • §

    Dr. Sorscher serves as a consultant for a Birmingham start up company (PNP Therapeutics, Inc.) but is not employed by the company and draws no salary from the company. His consulting includes a role as Director/Officer. He acts as a consultant with the approval of UAB and the UAB CIRB. He is compensated for consulting with stock. This company has no relationship to the current article. Dr. Sorscher and Dr. Woodworth are inventors on a patent submitted regarding the possible activity of chloride secretagogues for therapy of sinus disease (Provisional Patent Application Under 35 U.S.C. §111(b) and 37 C.F.R. §1.53(c) in the United States Patent and Trademark Office). Dr. Woodworth is a consultant for Gyrus ENT, ArthroCare ENT, and is on the GlaxcoSmithKline speaker's bureau.

Abstract

Objectives/Hypothesis:

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.

Study Design:

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 (Δ ISC expressed as μA/cm2) in MNSE, representing Cl secretion, was significantly increased when compared to controls (19.04 ± 1.67 μA/cm2 vs. 1.8 ± 0.35 μA/cm2, 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. Laryngoscope, 2010

Get access to the full text of this article

Ancillary