Apigenin alleviates TGF-β1-induced nasal mucosa remodeling by inhibiting MAPK / NF-kB signaling pathways in chronic rhinosinusitis.

Background: Chronic rhinosinusitis is involved in tissue remodeling of nasal mucosa such as nasal myofibroblast differentiation and extracellular matrix production. Apigenin (4',5,7-trihydroxyflavone) is a bioflavonoid compound and has anti-tissue remodeling characteristics. The aims of this study were to evaluate the effect of apigenin on TGF-β1-induced myofibroblast differentiation and extracellular matrix accumulation and to determine the underlying mechanism.

Methods: Nasal fibroblasts and ex vivo nasal inferior turbinate tissues were stimulated with TGF-β1 with or without apigenin. The expression levels of α-SMA, fibronectin and collagen type I were determined by real-time PCR, western blot and immunocytochemical staining. Mitogen-activated protein kinase (MAPK) phosphorylation induced by TGF-β1 were determined by western blot analysis. The transcriptional activity of NF-κB was measured by luciferase assay. Migration effects of fibroblasts were evaluated by wound scratch and transwell migration assay. Contractile activity was determined by collagen gel contraction assay.

Results: The expression levels of α-SMA, fibronectin, and collagen type I significantly increased in TGF-β1-stimulated nasal fibroblasts. In TGF-β1-stimulated nasal fibroblasts, apigenin inhibited the expressions of α-SMA, fibronectin, and collagen type I. Inhibitors of MAPK (p-38, JNK) and NF-κB blocked the expression of α-SMA, fibronectin and collagen type I. Apigenin suppressed the activation of MAPK (p-38, JNK) and NF-κB induced by TGF-β1 treatment. Apigenin also inhibited the functional activity of fibroblasts by reducing the migration and collagen contractile activities.

Conclusions: These results suggests the possible use of apigenin as a chronic rhinosinusitis therapeutic agent which can suppress tissue remodeling in nasal mucosa.