Leonurine attenuates OVA-induced asthma via p38 MAPK/NF-κB signaling pathway.
Leonurine attenuates OVA-induced asthma via p38 MAPK/NF-κB signaling pathway.
复制标题
益母草碱通过p38丝裂原活化蛋白激酶（p38 MAPK）/核因子-κB（NF-κB）信号通路减轻卵清蛋白（OVA）诱导的哮喘。
DOI：
10.1016/j.intimp.2022.109483
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发表时间：
2022-12
影响因子：
5.6
通讯作者：
Donghui Bai;Yujie Sun;Qiong Li;Haihua Li;Y. Liang;Ximing Xu;Jie Hao
中科院分区：
文献类型：
--
作者：
Donghui Bai;Yujie Sun;Qiong Li;Haihua Li;Y. Liang;Ximing Xu;Jie Hao
益母草碱（Leo）是从益母草中提取的天然生物碱，具有多种生物活性。然而，益母草碱是否对哮喘具有保护作用仍不清楚。本研究的目的是探讨益母草碱对哮喘的保护作用。我们评估了其在 LPS 诱导的 RAW264.7 细胞和 OVA 诱导的哮喘小鼠中的治疗效果和相关信号转导。此外，我们利用网络药理学、分子对接和分子动力学模拟来验证实验结果。在 LPS 诱导的 RAW 264.7 细胞中，益母草碱显着减少 TNF-α 和 IL-6 的产生，并抑制 p38 MAPK/NF-κB 信号通路的激活。在 OVA 诱导的哮喘小鼠中，益母草碱减少了支气管肺泡灌洗液 (BALF) 中炎症细胞的数量，特别是中性粒细胞和嗜酸性粒细胞。益母草碱还可降低BALF中IL-4、IL-5、IL-13和血清中OVA-IgE的含量。益母草碱显着改善 OVA 诱导的炎症细胞浸润，并显着抑制粘液过度产生。此外，益母草碱还能抑制哮喘小鼠肺组织中p38 MAPK/NF-κB信号通路的激活。网络药理学表明p38 MAPKα是益母草碱治疗哮喘的潜在靶点。分子对接和分子动力学模拟表明，益母草碱可以稳定地结合p38 MAPKα蛋白。总之，益母草碱通过调节 p38 MAPK/NF-κB 信号通路减轻哮喘。
Leonurine (Leo) is a natural alkaloid extracted from Herba leonuri, which has many biological activities. However, whether leonurine has a protective effect on asthma remains unknown. The purpose of this study was to investigate the protective effect of leonurine on asthma. We evaluated its therapeutic effect and related signal transduction in LPS-induced RAW264.7 cells and OVA-induced asthmatic mice. In addition, we used network pharmacology, molecular docking and molecular dynamics simulation to verify the experimental results. In LPS-induced RAW 264.7 cells, leonurine significantly reduced the production of TNF-α and IL-6, and inhibited the activation of p38 MAPK/NF-κB signaling pathway. In OVA-induced asthmatic mice, leonurine decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF), particularly neutrophils and eosinophils. Leonurine also reduced the contents of IL-4, IL-5, IL-13 in the BALF and OVA-IgE in the serum. Leonurine remarkly improved OVA-induced inflammatory cell infiltration and significantly inhibited mucus overproduction. In addition, leonurine inhibited the activation of p38 MAPK/NF-κB signaling pathway in the lung tissues of asthmatic mice. Network pharmacology suggested that p38 MAPKα was a potential target of leonurine in the treatment of asthma. Molecular docking and molecular dynamics simulations indicated that leonurine could stably bind to p38 MAPKα protein. In summary, leonurine attenuated asthma by regulating p38 MAPK/NF-κB signaling pathway.