<i>Glycyrrhiza glabra</i> -Based Nasal Spray as a Novel Treatment for Chronic Rhinosinusitis with Nasal Polyps: Efficacy in Symptom Reduction and Epithelial-Mesenchymal Transition Modulation

<b>Background:</b> Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition that significantly impacts patients' quality of life, characterized by high recurrence rates and limited treatment efficacy. Standard therapies, including corticosteroid nasal sprays, saline irrigation, and endoscopic sinus surgery, often fail to provide sustained relief, highlighting the need for alternative therapeutic strategies. <i>Glycyrrhiza glabra</i> (<i>G. glabra</i>), a traditional herbal remedy with documented anti-inflammatory and immunomodulatory effects, has shown potential in modulating inflammation in various respiratory and inflammatory conditions. This study evaluates the efficacy and mechanism of a novel <i>G. glabra</i>-based nasal spray for CRSwNP treatment, focusing on its anti-inflammatory and epithelial-mesenchymal transition (EMT)-reversing effects. <b>Methods:</b> A total of 30 CRSwNP patients were enrolled and underwent a two-month single-regimen treatment with the <i>G. glabra</i> nasal spray without concomitant CRS medications, administered twice daily. Clinical outcomes were assessed via the Total Nasal Symptom Score (TNSS), Sinonasal Outcome Test-22 (SNOT-22), and nasal endoscopy. Histopathological evaluation was performed on nasal polyp biopsies from 15 patients pre- and post-treatment using immunohistochemistry (IHC) and immunofluorescence (IF) staining for mesenchymal and epithelial markers. <b>Results:</b> Results demonstrated significant improvement in TNSS and SNOT-22 scores, alongside visible reduction in polyp size. IHC and IF analyses revealed reduced expression of mesenchymal markers (α-SMA, vimentin, fibronectin) and increased expression of epithelial markers (E-cadherin, EpCAM), indicating EMT reversal. No adverse effects were reported. <b>Conclusion:</b> These findings suggest that <i>G. glabra</i> nasal spray may offer a safe and effective treatment option for CRSwNP, potentially acting through EMT modulation. Further studies with larger cohorts are recommended to refine patient stratification and explore the molecular basis of differential treatment responses.