Osthole Ameliorates Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition via PI3K/Akt/NF-κB Pathway in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION

Osthole, a naturally occurring coumarin derivative, has been isolated from the traditional Chinese medicinal herb Cnidium monnieri. This compound exhibits a range of pharmacological properties, including anticancer, antioxidant, anti-inflammatory, and immunomodulatory effects. The objective of this study was to investigate the role of osthole in tissue remodeling in chronic rhinosinusitis with nasal polyp (CRSwNP).

METHODS

The effects of osthole on nasal polyp (NP) formation were examined within a mouse model of NPs induced by cigarette smoke (CS). The detection of polypoid changes and goblet cell metaplasia was achieved through the use of hematoxylin-eosin and periodic acid-Schiff staining, respectively. The levels of TGF-β1, matrix metalloproteinases 2, 7, 9, and 12 (MMP2, MMP7, MMP9, MMP12), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) in nasal lavage fluid were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was employed to ascertain the expression of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, α-SMA, and vimentin), as well as the activity of the PI3K/AKT/NF-κB pathway. The expression of E-cadherin in nasal epithelium was determined through immunohistochemistry.

RESULTS

In the OVA+SEB or CS-exposed NP mouse model, osthole was observed to reduce the incidence of polypoid changes and goblet cells, while simultaneously increasing the expression of E-cadherin in the epithelium when compared to the CS-treated group. After treatment with osthole, the levels of TGF-β1, MMP2, MMP7, MMP9, and MMP12 in nasal lavage fluid were observed to decrease, while the levels of TIMP-1 were found to increase. In vitro, cigarette smoke extract was observed to downregulate the expression of E-cadherin and ZO-1, while simultaneously upregulating the expression of α-SMA and vimentin. Moreover, osthole upregulated the expression of E-cadherin and ZO-1 while downregulating the expression of α-SMA and vimentin. This effect of osthole was reversed by PI3K/AKT/NF-κB pathway agonists.

CONCLUSION

Osthole attenuates CS exposure-induced EMT via the PI3K/AKT/NF-κB pathway, providing a theoretical and experimental basis for its clinical application in the treatment of CRSwNP.