Leonurine attenuates OVA-induced asthma via p38 MAPK/NF-κB signaling pathway

• Published in: International immunopharmacology Vol. 114; p. 109483
• Main Authors: Bai, Donghui, Sun, Yujie, Li, Qiong, Li, Haihua, Liang, Yuerun, Xu, Ximing, Hao, Jiejie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2023
• Subjects: Animals; Asthma; Asthma - chemically induced; Asthma - drug therapy; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Leonurine; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Network pharmacology; NF-kappa B - metabolism; NF-κB; Ovalbumin - therapeutic use; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; Signal Transduction; NF-κB; Network pharmacology; Leonurine; p38 MAPK; Asthma
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.109483

[Display omitted] •Leonurine (Leo) is a natural alkaloid extracted from Herba leonuri.•Leonurine could effectively alleviate asthma by regulating p38 MAPK/NF-κB signaling pathway.•Leonurine may be a promising drug for the treatment of asthma. 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, andinhibited 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.