Formononetin ameliorates IL‑13‑induced inflammation and mucus formation in human nasal epithelial cells by activating the SIRT1/Nrf2 signaling pathway.

Abstract

Formononetin has proven to be anti-inflammatory and able to alleviate symptoms of certain allergic diseases. The present study aimed to determine and elucidate the potential effects of formononetin in allergic rhinitis. JME/CF15 cells were pretreated with formononetin at different doses, followed by stimulation with IL-13. Cell Counting Kit-8 assay was performed to determine the cytotoxicity of formononetin. The expression levels of inflammation-related proteins, histamine, IgE, TNF-α, IL-1β, IL-6, granulocyte-macrophage colony-stimulating factor and eotaxin in IL-13-stimulated JME/CF15 cells were detected using ELISAs. The expression levels of phosphorylated-NF-κB p65, NF-κB p65 and cyclooxygenase-2 (Cox-2) were analyzed using western blotting. Reverse transcription-quantitative PCR, western blotting and immunofluorescence were performed to measure the levels of mucin 5AC oligomeric mucus/gel-forming. Expression levels of sirtuin 1 (SIRT1) and nuclear erythroid factor 2-related factor 2 (Nrf2) proteins were also measured using western blotting. The results of the present study revealed that formononetin exerted no cytotoxic effect on the viability of JME/CF15 cells. Following stimulation of JME/CF15 cells with IL-13, formononetin suppressed the upregulated expression levels of proinflammatory cytokines. IL-13-induced formation of mucus was also attenuated by formononetin treatment. Furthermore, it was found that the SIRT1/Nrf2 signaling pathway was activated in formononetin-treated JME/CF15 cells, whereas treatment with the SIRT1 inhibitor, EX527, reversed the effects of formononetin on IL-13-induced inflammation and mucus formation in JME/CF15 cells. In conclusion, the findings of the current study indicated that formononetin may activate the SIRT1/Nrf2 signaling pathway, thereby inhibiting IL-13-induced inflammation and mucus formation in JME/CF15 cells. These results suggested that formononetin may represent a promising agent for the treatment of allergic rhinitis.