Evidence map›Paper›PMID 25117505›Full record

ArticlePloS one2014

Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport and improves indicators of mucociliary clearance.

Shaoyan Zhang, Daniel Skinner, Stephen Bradley Hicks, Mark O Bevensee, Eric J Sorscher, Ahmed Lazrak, Sadis Matalon, Carmel M McNicholas, Bradford A Woodworth

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 69 citations in OpenAlex.

  1. [Transmembrane protein 16A--a new target for the treatment of airway inflammatory diseases].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025
    Review
  2. Lipopolysaccharide Causes Acquired CFTR Dysfunction in Murine Nasal Airways.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Article
  3. Article
  4. Article
  5. Review
  6. Red ginseng aqueous extract improves mucociliary transport dysfunction and histopathology in CF rat airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Antibiotic eluting sinus stents.Laryngoscope investigative otolaryngology · 2020
    Review
  16. Intracellular ClInternational journal of molecular sciences · 2020
    Review
  17. Article
  18. Article
  19. Daidzein-Stimulated Increase in the Ciliary Beating Amplitude via an [ClInternational journal of molecular sciences · 2018
    Article
  20. Acquired cystic fibrosis transmembrane conductance regulator dysfunction.World journal of otorhinolaryngology - head and neck surgery · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Shaoyan ZhangDepartments of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Daniel SkinnerDepartments of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Stephen Bradley HicksDepartments of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Mark O BevenseeGregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Eric J SorscherGregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Ahmed LazrakDepartment of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Sadis MatalonDepartment of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Carmel M McNicholasDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Bradford A WoodworthDepartments of Surgery/Division of Otolaryngology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
University of Alabama at Birmingham · US

Funding

UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI AMIT GAGGAR · 2007 to 2026
$23.0M
PATHOPHYSIOLOGY OF SUBLETHAL OXYGEN IN INJURED LUNGSR01HL031197 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MARK N GILLESPIE, Sadis Matalon · 1985 to 2026
$4.2M
Chloride secretagogues for acquired CFTR dysfunction in chronic rhinosinusitisK08HL107142 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WOODWORTH, BRADFORD ALAN · 2011 to 2015
$668k
NHLBI NIH HHS 1K08HL107142-04NHLBI NIH HHS 2R01HL031197NHLBI NIH HHS K08 HL107142NHLBI NIH HHS R01 HL031197NIDDK NIH HHS 5P30DK072482-03NIDDK NIH HHS P30 DK072482
6 · The paper itself

Abstract

introductionWe have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl-) secretion in vitro and in vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC) including ciliary beat frequency (CBF) and airway surface liquid (ASL) depth, but also investigate the mechanisms that underlie activity of this bioflavonoid.

methodsPrimary murine nasal septal epithelial (MNSE) [wild type (WT) and transgenic CFTR(-/-)], human sinonasal epithelial (HSNE), WT CFTR-expressing CFBE and TMEM16A-expressing HEK cultures were utilized for the present experiments. CBF and ASL depth measurements were performed. Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers, Fura-2 intracellular calcium [Ca(2+)]i imaging, cAMP signaling, regulatory domain (R-D) phosphorylation of CFTR, and excised inside out and whole cell patch clamp analysis.

resultsSinupret-mediated Cl- secretion [ΔISC(µA/cm(2))] was pronounced in WT MNSE (20.7+/-0.9 vs. 5.6+/-0.9(control), p<0.05), CFTR(-/-) MNSE (10.1+/-1.0 vs. 0.9+/-0.3(control), p<0.05) and HSNE (20.7+/-0.3 vs. 6.4+/-0.9(control), p<0.05). The formulation activated Ca(2+) signaling and TMEM16A channels, but also increased CFTR channel open probability (Po) without stimulating PKA-dependent pathways responsible for phosphorylation of the CFTR R-domain and resultant Cl- secretion. Sinupret also enhanced CBF and ASL depth.

conclusionSinupret stimulates CBF, promotes transepithelial Cl- secretion, and increases ASL depth in a manner likely to enhance MCC. Our findings suggest that direct stimulation of CFTR, together with activation of Ca(2+)-dependent TMEM16A secretion account for the majority of anion transport attributable to Sinupret. These studies provide further rationale for using robust Cl- secretagogue based therapies as an emerging treatment modality for common respiratory diseases of MCC including acute and chronic bronchitis and CRS.

Indexed as

AnimalsAnoctamin-1CalciumChloride ChannelsChloridesCiliaCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHumansIon TransportMiceMucociliary ClearanceNeoplasm ProteinsPatch-Clamp TechniquesANO1 protein, humanANO1 protein, mouseAnoctamin-1CalciumChloride ChannelsChloridesCyclic AMPCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorNeoplasm ProteinsPlant ExtractsSinupret

Identifiers

PMID25117505
PMCPMC4130514
OpenAlexW2112530308

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.