Department of Traditional Chinese Medicine, The Affiliated People's Hospital of Ningbo University, Ningbo, Zhejiang 315040, P.R. China.
Mol Med Rep. 2021 Dec;24(6). doi: 10.3892/mmr.2021.12472. Epub 2021 Sep 30.
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.
芒柄花素已被证明具有抗炎作用，并能缓解某些过敏性疾病的症状。本研究旨在确定并阐明芒柄花素在过敏性鼻炎中的潜在作用。用不同剂量的芒柄花素预处理 JME/CF15 细胞，然后用 IL-13 刺激。用细胞计数试剂盒-8 测定芒柄花素的细胞毒性。用 ELISA 检测 IL-13 刺激的 JME/CF15 细胞中炎症相关蛋白、组胺、IgE、TNF-α、IL-1β、IL-6、粒细胞-巨噬细胞集落刺激因子和嗜酸性粒细胞趋化因子的表达水平。用 Western blot 分析磷酸化 NF-κB p65、NF-κB p65 和环氧化酶-2（Cox-2）的表达水平。用逆转录-定量 PCR、Western blot 和免疫荧光法测定粘蛋白 5AC 寡聚粘液/凝胶形成的水平。用 Western blot 法测定 Sirtuin 1（SIRT1）和核红细胞因子 2 相关因子 2（Nrf2）蛋白的表达水平。本研究结果表明，芒柄花素对 JME/CF15 细胞的活力没有细胞毒性作用。在 JME/CF15 细胞被 IL-13 刺激后，芒柄花素抑制了促炎细胞因子的上调表达。芒柄花素处理也减弱了 IL-13 诱导的粘液形成。此外，研究发现，在芒柄花素处理的 JME/CF15 细胞中激活了 SIRT1/Nrf2 信号通路，而用 SIRT1 抑制剂 EX527 处理则逆转了芒柄花素对 JME/CF15 细胞中 IL-13 诱导的炎症和粘液形成的作用。综上所述，本研究结果表明，芒柄花素可能通过激活 SIRT1/Nrf2 信号通路，抑制 JME/CF15 细胞中 IL-13 诱导的炎症和粘液形成。这些结果表明，芒柄花素可能是治疗过敏性鼻炎的一种有前途的药物。
