Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-κB and MAPK and Activating Nrf2 Signaling Pathways in Mice.
Eupatilin Suppresses OVA-Induced Asthma by Inhibiting NF-κB and MAPK and Activating Nrf2 Signaling Pathways in Mice.
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DOI：
10.3390/ijms23031582
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发表时间：
2022-01-29
影响因子：
5.6
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Bai D;Sun T;Lu F;Shen Y;Zhang Y;Zhang B;Yu G;Li H;Hao J
为了研究尤帕替林在哮喘治疗中的作用，我们评估了其在 OVA 诱导的哮喘小鼠和 LPS 刺激的 RAW264.7 细胞中的治疗效果和相关信号转导。测试 BALF 中肺部炎症细胞的变化。采用ELISA法测定BALF中的Th2细胞因子和血清中的OVA-IgE。 H&E 和 PAS 染色用于评估小鼠肺部的组织病理学变化。采用Western blotting定量分析肺组织中关键蛋白NF-κB、MAPK和Nrf2。最后，我们在体外评估了 eupatilin 对 LPS 刺激的 RAW 264.7 细胞中细胞因子和相关蛋白表达的影响。在 OVA 诱导的哮喘小鼠中，eupatilin 减少了炎症细胞的数量，尤其是中性粒细胞和嗜酸性粒细胞。 Eupatilin 还降低 BALF 中 IL-5、IL-13 和血清中 OVA-IgE 的水平。此外，eupatilin 抑制 NF-κB 和 MAPK 通路的激活，并增加 OVA 诱导的哮喘小鼠中 Nrf2 的表达。在体外，eupatilin 显着减少 LPS 刺激的 NO、IL-6 和 ROS 的产生。此外，LPS刺激的RAW264.7细胞中NF-κB、MAPK和Nrf2蛋白的表达与OVA诱导的哮喘肺组织中的一致。总之，eupatilin 通过调节 NF-κB、MAPK 和 Nrf2 信号通路减轻 OVA 诱导的哮喘。这些结果表明尤帕替林作为抗炎药用于哮喘治疗的效用。
To investigate the effect of eupatilin in asthma treatment, we evaluated its therapeutic effect and related signal transduction in OVA-induced asthmatic mice and LPS-stimulated RAW264.7 cells. The BALF was tested for changes in lung inflammatory cells. Th2 cytokines in the BALF and OVA-IgE in the serum were measured by ELISA. H&E and PAS staining were used to evaluate histopathological changes in mouse lungs. The key proteins NF-κB, MAPK, and Nrf2 in lung tissues were quantitatively analyzed by Western blotting. Finally, we evaluated the effect of eupatilin on cytokines and related protein expression in LPS-stimulated RAW 264.7 cells in vitro. In OVA-induced asthmatic mice, eupatilin reduced the numbers of inflammatory cells, especially neutrophils and eosinophils. Eupatilin also decreased the levels of IL-5, IL-13 in the BALF and OVA-IgE in the serum. Furthermore, eupatilin inhibited the activation of NF-κB and MAPK pathways and increased the expression of Nrf2 in OVA-induced asthmatic mice. In vitro, eupatilin significantly reduced LPS-stimulated NO, IL-6, and ROS production. Additionally, the NF-κB, MAPK, and Nrf2 protein expression in LPS-stimulated RAW264.7 cells was consistent with that in OVA-induced asthmatic lung tissues. In summary, eupatilin attenuated OVA-induced asthma by regulating NF-κB, MAPK, and Nrf2 signaling pathways. These results suggest the utility of eupatilin as an anti-inflammatory drug for asthma treatment.
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