Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis
Do‐Yeon Cho MD Daniel Skinner BS Calvin Mackey BS Harold B Lampkin BS Jeffrey Brent Elder BS Dong Jin Lim PhD Shaoyan Zhang PhD Justin McCormick MD … See all authors
First published: 18 January 2019 https://doi.org/10.1002/alr.22290
Funding sources for the study: Bionorica SE (Neumarkt, Germany) (to D.Y.C. and B.A.W.); NIH (National Heart, Lung, and Blood Institute [NHLBI] 1 R01 HL133006‐03 to B.A.W; National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] 5P30DK072482‐05 to B.A.W.); Cystic Fibrosis Foundation CF Research Center Pilot Award (to B.A.W.); John W. Kirklin Research and Education Foundation Fellowship Award to D.Y.C.; UAB Faculty Development Research Award (to D.Y.C.); American Rhinologic Society New Investigator Award (to D.Y.C.); Cystic Fibrosis Foundation Research Development Pilot Grant ROWE15R0 to D.Y.C.)
Presented at the Annual ARS Meeting on October 5‐6, 2018, in Atlanta, GA.
Potential conflict of interest: D.Y.C. receives research grant support from Bionorica SE. B.A.W. is a consultant for Olympus and Cook Medical; he also receives grant support from Cook Medical and Bionorica SE.
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Abstract
Background
Enhancing chloride (Cl–) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl– secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS.
Methods
After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl− secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro‐optical coherence tomography (μOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators.
Results
BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = –12.23 ± 1.4 mV, LD = –12.0 ± 3.0 mV) when compared to rabbits treated with placebo (–4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 μm) and LD (4.05 ± 0.06 μm) compared to placebo (3.5 ± 0.05 μm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 μm; LD = 13.7 ± 0.9 μm; placebo = 21.1 ± 2.3 μm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 μm; LD = 103.2 ± 6.7 μm; placebo = 113.3 ± 6.0 μm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD.
Conclusion
Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.
Do‐Yeon Cho MD Daniel Skinner BS Calvin Mackey BS Harold B Lampkin BS Jeffrey Brent Elder BS Dong Jin Lim PhD Shaoyan Zhang PhD Justin McCormick MD … See all authors
First published: 18 January 2019 https://doi.org/10.1002/alr.22290
Funding sources for the study: Bionorica SE (Neumarkt, Germany) (to D.Y.C. and B.A.W.); NIH (National Heart, Lung, and Blood Institute [NHLBI] 1 R01 HL133006‐03 to B.A.W; National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] 5P30DK072482‐05 to B.A.W.); Cystic Fibrosis Foundation CF Research Center Pilot Award (to B.A.W.); John W. Kirklin Research and Education Foundation Fellowship Award to D.Y.C.; UAB Faculty Development Research Award (to D.Y.C.); American Rhinologic Society New Investigator Award (to D.Y.C.); Cystic Fibrosis Foundation Research Development Pilot Grant ROWE15R0 to D.Y.C.)
Presented at the Annual ARS Meeting on October 5‐6, 2018, in Atlanta, GA.
Potential conflict of interest: D.Y.C. receives research grant support from Bionorica SE. B.A.W. is a consultant for Olympus and Cook Medical; he also receives grant support from Cook Medical and Bionorica SE.
Read the full text
ePDFPDFTOOLS SHARE
Abstract
Background
Enhancing chloride (Cl–) secretion in sinus epithelia represents a novel therapeutic approach to chronic rhinosinusitis (CRS). Herbal dry extract BNO 1011 enhances mucociliary clearance (MCC) via upregulation of Cl– secretion in sinonasal cultures in vitro and murine epithelium in vivo. The objective of this study is to evaluate whether the BNO 1011 improves MCC and clinical parameters in a rabbit model of CRS.
Methods
After the development of CRS in 30 New Zealand white rabbits, animals were randomly assigned to receive oral placebo (n = 10), BNO 1011 (low dose [LD], 25 mg/kg/daily) (n = 10), or BNO1011 (high dose [HD], 125 mg/kg/daily) (n = 10) for 4 weeks. Outcomes included sinus opacification (Kerschner's rabbit sinus CT grade), maxillary epithelial Cl− secretion (sinus potential difference [PD] assay), airway surface liquid (ASL) depth using micro‐optical coherence tomography (μOCT), and submucosal gland density (SMD) on histopathology. Outcome parameters were analyzed by 2 blinded investigators.
Results
BNO 1011 significantly cleared sinus opacification (HD = 1.21 ± 0.63, LD = 1.26 ± 0.37,) compared to placebo (4.02 ± 0.92) (p = 0.009). BNO 1011 resulted in markedly greater mean sinus PD polarization (HD = –12.23 ± 1.4 mV, LD = –12.0 ± 3.0 mV) when compared to rabbits treated with placebo (–4.1 ± 1.1 mV) (p = 0.03). ASL depth was significantly improved when treated with HD (4.08 ± 0.06 μm) and LD (4.05 ± 0.06 μm) compared to placebo (3.5 ± 0.05 μm) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 ± 0.7 μm; LD = 13.7 ± 0.9 μm; placebo = 21.1 ± 2.3 μm; p < 0.005), subepithelial thickness (HD = 63.1 ± 6.6 μm; LD = 103.2 ± 6.7 μm; placebo = 113.3 ± 6.0 μm; p < 0.001), and SMD (HD = 22.2 ± 2.9%; LD = 31.8 ± 1.1%; placebo = 43.8 ± 1.7%; p < 0.0001) were noticeably better with the HD.
Conclusion
Herbal dry extract BNO 1011 improves radiographic, histologic, and MCC parameters in a rabbit model of CRS.
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