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

Do-Yeon Cho; Daniel Skinner; Shaoyan Zhang; Ahmed Lazrak; Dong Jin Lim; Christopher G Weeks; Catherine G Banks; Chang Kyun Han; Si-Kwan Kim; Guillermo J Tearney; Sadis Matalon; Steven M Rowe; Bradford A Woodworth

doi:10.1016/j.jgr.2019.09.001

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

J Ginseng Res. 2021 Jan;45(1):66-74. doi: 10.1016/j.jgr.2019.09.001. Epub 2019 Sep 13.

Authors

Do-Yeon Cho^{1

2}, Daniel Skinner¹, Shaoyan Zhang¹, Ahmed Lazrak^{2

3}, Dong Jin Lim¹, Christopher G Weeks¹, Catherine G Banks¹, Chang Kyun Han⁴, Si-Kwan Kim⁵, Guillermo J Tearney⁶, Sadis Matalon^{2

3}, Steven M Rowe^{2

7}, Bradford A Woodworth^{1

2}

Affiliations

¹ Department of Otolaryngology Head & Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, United States.
² Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States.
³ Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States.
⁴ Korea Ginseng Research Institute, Korea Ginseng Corporation, Daejeon, Republic of Korea.
⁵ Department of Biomedical Chemistry, Konkuk University, Chungju, Republic of Korea.
⁶ Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States.
⁷ Departments of Medicine, Pediatrics, Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, United States.

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 30μg/mL of ginsenosides) significantly increased Cl^- transport [measured as change in short-circuit current (ΔI_SC = μA/cm²)] 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 ΔI_SC 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 μm vs control, 3.9+/-0.09 μm; 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: CFTR; Chloride channels; Mucociliary clearance; Red Ginseng; Sinusitis.

Abstract

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