Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Department of Rhinology and Allergy, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Department of Rhinology and Allergy, Renmin Hospital of Wuhan University, Wuhan, China; Hubei Province Key Laboratory of Allergy and Immunology, Wuhan, China.
Biomed Pharmacother. 2024 Nov;180:117547. doi: 10.1016/j.biopha.2024.117547. Epub 2024 Oct 13.
Previous studies have indicated that oridonin is a promising candidate for therapeutic intervention in a range of inflammatory diseases. The objective of this study was to investigate the protective mechanism of oridonin in chronic rhinosinusitis with nasal polyp (CRSwNP). In nasal polyp (NP) mice model, cigarette smoke (CS) induced polypoid changes compared to previous modeling methods. Compared with CS-treated mice, oridonin reduced polypoid changes, goblet cell count, and promoted the expression of tight junction proteins (ZO-1, occludin, claudin-1) and production of autophagosomes. Following treatment with oridonin, the levels of OVA-specific IgE, IL-6, IFN-γ, IL-5, IL-13 and IL-17A in serum were observed to decrease; the levels of TGF-β1, matrix metalloproteinase 2 (MMP2), MMP7, MMP9 and MMP12 levels in nasal lavage fluid were reduced, while tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were increased. Furthermore, the aforementioned alterations in the mouse model were reversed by 3-methyladenine (3-MA), an autophagy inhibitor. In vitro, cigarette smoke extract (CSE) was observed to decrease the expression of tight junction proteins, the production of autophagosomes, and to reduce the expression of LC3-II and Beclin-1, accompanied by an increase in P62 expression. In addition, oridonin was observed to reverse CSE-induced epithelial barrier damage, and was associated with autophagy and the PI3K/AKT/mTOR pathway. In conclusion, oridonin was demonstrated to improve the damage of the nasal epithelial barrier induced by CS through the promotion of autophagy, which may represent a novel therapeutic option for the treatment of CRSwNP.
先前的研究表明，冬凌草甲素在一系列炎症性疾病的治疗干预中具有广阔的应用前景。本研究旨在探讨冬凌草甲素在慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中的保护机制。在鼻息肉（NP）小鼠模型中，与先前的建模方法相比，香烟烟雾（CS）诱导息肉样改变。与 CS 处理的小鼠相比，冬凌草甲素减少了息肉样改变、杯状细胞计数，并促进了紧密连接蛋白（ZO-1、occludin、claudin-1）的表达和自噬体的产生。经冬凌草甲素治疗后，血清中 OVA 特异性 IgE、IL-6、IFN-γ、IL-5、IL-13 和 IL-17A 水平降低；鼻洗液中 TGF-β1、基质金属蛋白酶 2（MMP2）、MMP7、MMP9 和 MMP12 水平降低，组织金属蛋白酶抑制剂-1（TIMP-1）水平升高。此外，自噬抑制剂 3-甲基腺嘌呤（3-MA）逆转了上述小鼠模型的变化。体外观察到香烟烟雾提取物（CSE）降低了紧密连接蛋白的表达、自噬体的产生，并降低了 LC3-II 和 Beclin-1 的表达，同时增加了 P62 的表达。此外，冬凌草甲素可逆转 CSE 诱导的上皮屏障损伤，并与自噬和 PI3K/AKT/mTOR 通路有关。综上所述，冬凌草甲素通过促进自噬，改善 CS 诱导的鼻上皮屏障损伤，可能为治疗 CRSwNP 提供一种新的治疗选择。
