芹菜素通过抑制 TLR4/MyD88/NF-κB 信号通路减轻变应性鼻炎小鼠的炎症反应。
Apigenin attenuates inflammatory response in allergic rhinitis mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
机构信息
Department of Otolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Pharmacy, Affiliated Hospital of Medical College of Xi'an Jiaotong University, Shaanxi Provincial Cancer Hospital, Xi'an, China.
出版信息
Environ Toxicol. 2023 Feb;38(2):253-265. doi: 10.1002/tox.23699. Epub 2022 Nov 9.
BACKGROUND
Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune inflammatory response that mainly affects the nasal mucosa. Currently, there is evidence that apigenin, as a flavonoid, has anti-allergic potential.
MATERIAL/METHODS: In vitro, compound 48/80 and lipopolysaccharide (LPS) were used to induce mast cell activation and inflammation in HMC-1 cells. In vivo, ovalbumin (OVA) induced and stimulated AR in BALB/c mice. ELISA was used to detect the contents of β-hexosaminidase, histamine, eosinophil cationic protein (ECP), OVA-specific IgE, IgG1, and IgG2a, inflammatory factors in cells and mouse serum. Cell viability and apoptosis were measured with MTT and flow cytometry. Toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/Nuclear transcription factor-κB (NF-κB) pathway-related proteins in cells and mouse nasal mucosa tissues were analyzed with Western blotting. The levels of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines and Th1 (T-bet) and Th2 (GATA-3) specific transcription factors were also assessed. The ratio of Th1 (CD4 IFN-γ ) / Th2 (CD4 IL-4 ) cells in mouse peripheral blood mononuclear cells was evaluated by flow cytometry.
RESULTS
Apigenin significantly inhibited compound 48/80-induced secretion of β-hexosaminidase and histamine. Apigenin blocked LPS-induced decrease in cell viability and increase in cell apoptosis and inflammatory cytokine secretion by suppressing the activity of the TLR4/MyD88/NF-κB pathway. Apigenin treatment reduced the levels of OVA-specific IgE, IgG1 and IgG2a as well as β-hexosaminidase, histamine and ECP levels in mouse serum. Moreover, administration with apigenin decreased Th2 cytokine and transcription factor levels and increased Th1 cytokine and transcription factor levels, and promoted the ratio of Th1/Th2 cells in AR mice. Additionally, apigenin significantly alleviated nasal symptoms and nasal eosinophil infiltration in AR mice.
CONCLUSIONS
Apigenin alleviates the inflammatory response of allergic rhinitis by inhibiting the activity of the TLR4/MyD88/NF-κB signaling pathway.
背景
过敏性鼻炎（AR）是一种免疫球蛋白 E（IgE）介导的免疫炎症反应，主要影响鼻黏膜。目前有证据表明，作为一种黄酮类化合物，芹菜素具有抗过敏的潜力。
材料/方法：在体外，使用化合物 48/80 和脂多糖（LPS）诱导 HMC-1 细胞中的肥大细胞活化和炎症。在体内，卵清蛋白（OVA）诱导并刺激 BALB/c 小鼠的 AR。ELISA 用于检测β-己糖胺酶、组胺、嗜酸性粒细胞阳离子蛋白（ECP）、OVA 特异性 IgE、IgG1 和 IgG2a、细胞和小鼠血清中的炎症因子的含量。用 MTT 和流式细胞术测量细胞活力和细胞凋亡。用 Western blot 分析细胞和小鼠鼻黏膜组织中的 Toll 样受体 4（TLR4）/髓样分化因子 88（MyD88）/核转录因子-κB（NF-κB）通路相关蛋白。还评估了 Th1（IFN-γ）和 Th2（IL-4、IL-5 和 IL-13）细胞因子以及 Th1（T-bet）和 Th2（GATA-3）特异性转录因子的水平。通过流式细胞术评估小鼠外周血单个核细胞中 Th1（CD4 IFN-γ）/Th2（CD4 IL-4）细胞的比值。
结果
芹菜素显著抑制化合物 48/80 诱导的β-己糖胺酶和组胺分泌。芹菜素通过抑制 TLR4/MyD88/NF-κB 通路的活性，阻断 LPS 诱导的细胞活力降低和细胞凋亡增加以及炎症细胞因子分泌。芹菜素治疗降低了小鼠血清中 OVA 特异性 IgE、IgG1 和 IgG2a 以及β-己糖胺酶、组胺和 ECP 的水平。此外，给予芹菜素降低了 Th2 细胞因子和转录因子水平，增加了 Th1 细胞因子和转录因子水平，并促进了 AR 小鼠中 Th1/Th2 细胞的比值。此外，芹菜素显著缓解了 AR 小鼠的鼻部症状和鼻嗜酸性粒细胞浸润。
结论
芹菜素通过抑制 TLR4/MyD88/NF-κB 信号通路的活性，缓解过敏性鼻炎的炎症反应。
Zotero 插件