Effects of BNO 1016 on ciliary transport velocity and cell culture surface liquid height of sinonasal epithelial cultures

Alan D Workman,David W Kennedy,Charles C L Tong,James N Palmer,Nithin D Adappa,Noam A Cohen,Edward C Kuan,Neil N Patel,Ivy W Maina,Vasiliki Triantafillou

doi:10.1186/s40816-021-00276-2

Abstract

BackgroundBNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-the-counter treatment for rhinosinusitis. Previous studies indicated activation of chloride secretion and increase in ciliary beat frequency by BNO 1016 but the functional consequences on mucociliary transport velocity and airway surface liquid homeostasis are unknown. This study intends to examine the effects of BNO 1016 on these properties in vitro.ResultsHuman sinonasal epithelial cells were grown at an air-liquid interface, with addition of BNO 1016 basolaterally in each experiment. Polystyrene fluorescent microspheres were added to the apical surface of the culture, and distance traveled across the surface of the culture over a fixed time period was measured using live imaging. BNO 1016 concentrations of 50 μg/ml and 500 μg/ml were tested. Basolateral application of compound resulted in a non-dose-dependent increase in culture surface liquid height compared to controls at 30 min, and this effect persisted through the one-hour duration of the experiment (p < 0.01). Basolateral application of BNO 1016 also resulted in a non-dose-dependent increase in microsphere transport velocity at 45 and 60 min following compound application (p < 0.01).ConclusionsBasolateral application of BNO 1016 at a concentration mimicking post-ingestion serum levels appears to elicit increases in cell culture surface liquid height and mucociliary clearance, as assessed by microsphere transport velocity. These properties can potentially be leveraged for therapeutic efficacy in diseases affecting mucus production and mucociliary transport.

Highlights

BNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-thecounter treatment for rhinosinusitis
Air-liquid Interface (ALI) cultures We have previously described the culture of human nasal epithelial cells at an ALI [14, 15]
The extract was prepared at concentrations of 50 μg/ml and 500 μg/ml, and dissolved in 0.5% DMSO diluted with phosphate-buffered saline

Summary

Introduction

BNO 1016 is an ethanolic extract of a mixture of five herbs that has been sold in different formulations for decades in the European market and more recently, in the United States market as an over-thecounter treatment for rhinosinusitis. BNO 1016 extract formulations have been extensively studied, with several randomized trials demonstrating therapeutic benefit in rhinosinusitis [4,5,6] It is currently used for a variety of respiratory conditions to reduce acute and chronic sinonasal or lower airway symptoms, such as those observed in bronchitis [7]. In mouse nasal epithelial cells, airway surface hydration occurs in response to addition of BNO 1016 through chloride ion secretion through the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel [8, 12]. This transepithelial ion movement causes an increase in mucus layer depth due to accompanying fluid shifts. Chloride ion secretagogues are increasingly used for treatment of diseases with inadequate MCC, including COPD, asthma, and CRS [13]

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