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

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.

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.

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.

RGAE augments ASL depth and CBF by stimulating Cl^- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.