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Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

  • Cho, Do-Yeon (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Skinner, Daniel (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Zhang, Shaoyan (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Lazrak, Ahmed (Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham) ;
  • Lim, Dong Jin (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Weeks, Christopher G. (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Banks, Catherine G. (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham) ;
  • Han, Chang Kyun (Korea Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Kim, Si-Kwan (Department of Biomedical Chemistry, Konkuk University) ;
  • Tearney, Guillermo J. (Wellman Center for Photomedicine, Massachusetts General Hospital) ;
  • Matalon, Sadis (Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham) ;
  • Rowe, Steven M. (Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham) ;
  • Woodworth, Bradford A. (Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham)
  • Received : 2018.08.16
  • Accepted : 2019.09.06
  • Published : 2021.01.15

Abstract

Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

Keywords

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