Exploring the molecular mechanism of icariin improving spinal cord injury through network pharmacology combined with experimental verification.

Abstract

This study aimed to investigate the potential pharmacological effects of icariin (ICA) in the treatment of spinal cord injury (SCI). Network pharmacology was used to focus on the potential targets and biological processes of ICA in SCI. Molecular docking was used to verify the ability of ICA to bind to its core targets. Finally, valuate the efficacy and potential mechanisms of ICA in treating spinal cord injury through in vitro and in vivo experiments. A total of 37 targets were screened out, and core genes were screened out from the protein‒protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these targets are enriched mainly in response to hypoxia, regulation of the cellular response to stress, and the TGF-beta signaling pathway. Molecular docking analysis showed that ICA has good docking ability with core targets. In animal experiments, Basso, Beattie and Bresnahan scores, catwalk gait analysis, hematoxylin and eosin staining, and RT-qPCR showed that ICA can inhibit spinal cord inflammation and effectively improve the behavioral and histological recovery after SCI rats. Western blot and immunofluorescence showed that ICA can reduce astrocyte activation and downregulate the TGF-beta signaling pathway after SCI. In addition, ICA can promote axonal nerve elongation and promotes angiogenesis after spinal cord injury in rats. In vitro experiments revealed that ICA can inhibit TGFβ1-induced activation of the TGF-beta signaling pathway and astrocyte activation. ICA treats SCI through multiple targets and pathways. ICA plays a major role in protecting nerves, promoting angiogenesis, and inhibiting reactive astrocyte activation in the treatment of SCI.