Chung Jaein, Im Se Yeon, Park Soo-Kyoung, Heo Da Beom, Sung Han Wool John, Ohm Danielle, Chung Eun Hee, Park Jong-Tae, Kim Yong Min
Department of Otorhinolaryngology-Head & Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea.
Department of Otorhinolaryngology-Head & Neck Surgery, Chungnam National University Hospital, Daejeon, Korea.
Allergy Asthma Immunol Res. 2025 Jan;17(1):77-93. doi: 10.4168/aair.2025.17.1.77.
Inotodiol (22-hydroxy lanosterol), a unique component of chaga mushrooms, is believed to be a medicinal component with reported antitumor, antiviral, and anti-inflammatory properties. This study evaluated the therapeutic potential and underlying mechanisms of inotodiol in eosinophilic chronic rhinosinusitis (ECRS).
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 transcription-polymerase 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 via immunofluorescence, flow cytometry, and proteome profiler antibody array analysis.
Inotodiol significantly reduced the secretion of T2 cytokine and mast cell tryptase as well as the expression of Th 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.
Inotodiol could be a potential therapeutic agent for ECRS by modulating immune responses and reducing mucosal inflammation.
桦褐孔菌醇（22-羟基羊毛甾醇）是桦褐孔菌的一种独特成分，被认为是一种具有抗肿瘤、抗病毒和抗炎特性的药用成分。本研究评估了桦褐孔菌醇在嗜酸性粒细胞性慢性鼻-鼻窦炎（ECRS）中的治疗潜力及潜在机制。
使用雌性BALB/c小鼠建立ECRS小鼠模型。40只小鼠分为4组：对照组（n = 10）、溶剂处理的ECRS组（n = 10）、20 mg/kg桦褐孔菌醇处理的ECRS组（n = 10）和10 mg/kg地塞米松处理的ECRS组（n = 10）。分析小鼠的鼻灌洗液和组织样本中细胞因子和趋化因子的表达以及黏膜炎症的严重程度。采用酶联免疫吸附测定、定量逆转录-聚合酶链反应、组织病理学染色和免疫荧光技术。使用人嗜酸性粒细胞系（EoL-1）和分散的鼻息肉细胞（DNPCs）通过免疫荧光、流式细胞术和蛋白质组分析抗体芯片分析评估桦褐孔菌醇诱导的嗜酸性粒细胞凋亡。
桦褐孔菌醇显著降低了ECRS小鼠中T2细胞因子和肥大细胞类胰蛋白酶的分泌以及Th细胞因子、趋化因子和促炎/炎症细胞因子的表达。此外，它抑制了黏膜炎症特征，如息肉形成、上皮增厚和嗜酸性粒细胞浸润。桦褐孔菌醇处理降低了ECRS小鼠鼻黏膜中肥大细胞的活化并增加了嗜酸性粒细胞凋亡。值得注意的是，桦褐孔菌醇还诱导了EoL-1细胞和DNPCs的凋亡，这可能有助于其抗炎作用。
桦褐孔菌醇可能通过调节免疫反应和减轻黏膜炎症成为ECRS的一种潜在治疗药物。
