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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. |
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