The mechanisms of Chuanxiong Rhizoma in treating spinal cord injury based on network pharmacology and experimental verification.

Abstract

BackgroundChuanxiong Rhizoma (CR) is a common traditional Chinese medicine (TCM) that has been widely used in the treatment of spinal cord injury (SCI). However, the underlying molecular mechanism of CR is still largely unknown. This study was designed to explore the bioactive components and the mechanism of CR in treating SCI based on a network pharmacology approach and experimental validation.MethodsFirst, the active compounds and related target genes in CR were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the corresponding target genes of SCI were collected by the Therapeutic Target Database (TTD) and GeneCards database. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, GO function and KEGG enrichment analysis of the targets were analyzed using DAVID tools. Subsequently, the AutoDock software for molecular docking was adopted to verify the above network pharmacology analysis results between the active components and key targets. Finally, an SCI rat model animal validation experiment was assessed to verify the reliability of the network pharmacology results.ResultsThere were 7 active ingredients identified in CR and 246 SCI-related targets were collected. Then, 4 core nodes (ALB, AKT1, MAPK1, and EGFR) were discerned via construction of a PPI network of 111 common targets. The KEGG enrichment analysis results indicated that the Ras signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor (VEGF) signaling pathway were enriched in the development of SCI. The results of molecular docking demonstrated that the effects of CR have a strong affinity with the 4 pivotal targets. Experimental validation in a rat model showed that CR could effectively improve the recovery of motor function and mechanical pain threshold after SCI.ConclusionsIn summary, it revealed the mechanism of CR treatment for SCI involve active ingredients, targets and signaling pathways, providing a scientific basis for future investigations into the mechanism underlying CR treating for SCI.