Icariin ameliorates LPS-induced acute lung injury in mice via complement C5a-C5aR1 and TLR4 signaling pathways

• Published in: International immunopharmacology 2024-04, Vol.131, p.111802-111802, Article 111802
• Main Authors: Guo, Jing, Zhang, Qi-Yun, Xu, Lin, Li, Min, Sun, Qian-Yun
• Format: Article
• Language: English
• Subjects: Acute lung injury; Complement; Icariin; Inflammation; Mitochondrial apoptosis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111802

[Display omitted] •Icariin restored LPS-induced lung inflammation and mitochondrial apoptosis.•Icariin improved immune inflammation through the complement C5a-C5aR1 axis.•Icariin alleviated lung injury by regulating TLR4 signaling pathways. Acute lung injury (ALI) is an acute respiratory-related progressive disorder, which lacks specific pharmacotherapy. Icariin (ICA) has been shown to be effective in treating ALI. However, the targets and pharmacological mechanisms underlying the effects of ICA in the treatment of ALI are relatively lacking. Based on network pharmacology and molecular docking analyses, the gene functions and potential target pathways of ICA in the treatment of ALI were determined. In addition, the underlying mechanisms of ICA were verified by immunohistochemistry, immunofluorescence, quantitative Real-time PCR, and Western blot in LPS-induced ALI mice. The biological processes targeted by ICA in the treatment of ALI included the pathological changes, inflammatory response, and cell signal transduction. Network pharmacology, molecular docking, and in vivo experimental results revealed that ICA inhibited the complement C5a-C5aR1 axis, TLR4 mediated NF-κB, MAPK, and JAK2-STAT3 signaling pathways related gene and protein expressions, and decreased inflammatory cytokine, chemokine, adhesion molecule expressions, and mitochondrial apoptosis in LPS-induced ALI.