Herbal dry extract BNO 1011 improves clinical and mucociliary parameters in a rabbit model of chronic rhinosinusitis

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 (mu OCT), 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 mu m) and LD (4.05 +/- 0.06 mu m) compared to placebo (3.5 +/- 0.05 mu m) (post hoc analysis, p < 0.0001). Histologically, epithelial thickness (HD = 10.0 +/- 0.7 mu m; LD = 13.7 +/- 0.9 mu m; placebo = 21.1 +/- 2.3 mu m; p < 0.005), subepithelial thickness (HD = 63.1 +/- 6.6 mu m; LD = 103.2 +/- 6.7 mu m; placebo = 113.3 +/- 6.0 mu m; 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. (C) 2019 ARS-AAOA, LLC.