Inotodiol Attenuates Mucosal Inflammation in a Mouse Model of Eosinophilic Chronic Rhinosinusitis

Purpose: Inotodiol (22-hydroxy lanosterol), a unique component of chaga mushrooms, is believed to be a medicinal component with reported antitumor, antiviral, and antiinflammatory properties. This study evaluated the therapeutic potential and underlying mechanisms ofinotodiol in eosinophilic chronic rhinosinusitis (ECRS). Methods: An ECRS mouse model was established using female BALB/c mice. Forty mice were categorized into 4 groups: the control group (n = 10), ECRS group treated with solvent (n = 10), ECRS group treated with inotodiol 20 mg/kg (n = 10), and ECRS group treated with dexamethasone 10 mg/kg (n = 10). The nasal lavage fluid and tissue samples from mice were analyzed for cytokine and chemokine expression as well as for the severity of mucosal inflammation. Enzyme-linked immunosorbent assay, quantitative reverse transcriptionpolymerase chain reaction, histopathological staining, and immunofluorescence techniques were employed. The human eosinophil cell line (EoL-1) and dispersed nasal polyp cells (DNPCs) were used to assess inotodiol-induced eosinophil apoptosis in vitro via immunofluorescence, flow cytometry, and proteome profiler antibody array analysis. Results: Inotodiol significantly reduced the secretion of T2 cytokine and mast cell tryptase as well as the expression ofTh cytokines, chemokines, and proinflammatory/inflammatory cytokines in ECRS mice. Furthermore, it suppressed mucosal inflammatory features such as polyp formation, epithelial thickening, and eosinophil infiltration. Inotodiol treatment reduced mast cell activation and increased eosinophil apoptosis in the nasal mucosa of ECRS mice. Notably, inotodiol also induced apoptosis in EoL-1 cells and DNPCs, which may contribute to its anti-inflammatory effects. Conclusions: Inotodiol could be a potential therapeutic agent for ECRS by modulating immune responses and reducing mucosal inflammation.