Molecular mechanism of rutin treatment for spinal cord injury based on network pharmacology and GEO differential gene chip data analysis
To explore the mechanism of rutin in the treatment of spinal cord injury(SCI),the targets of rutin in the treatment of SCI were screened based on network pharmacology and GEO differential gene chip data analysis combined with in vivo experi-ments.Firstly,the targets of rutin were obtained through TCMSP,Swiss Target Prediction,and SuperPred databases,and the disease targets for SCI were obtained through GEO differentially expressed genes,CTD,OMIM,and PharmaGkb disease databases.Then,Cytoscape software was used to screen the core targets of rutin for SCI by protein interaction,and R language was used to analyze the GO function and KEGG pathway enrichment of the core targets.Finally,a model of acute SCI in rat was established using Rutgers MASCIS SCI impactor,and the BBB motor score method was used to evaluate the hind limb motor function of rats after three days of intervention with rutin.The expression levels of TNF-α,IL-6,il-1β,NF-κb,and the contents of ROS and MDA in spinal cord homogenate were detected by enzyme-linked immunosorbent assay(Elisa).The results are as follows:①There are 56 cor-responding protein targets in rutin and 4 624 disease targets for SCI,and five core targets were obtained after merging,namely CASP3,ESR1,GSK3B,IL-6,MTOR;②GO function mainly focuses on the response to oxidative stress,reactive oxygen species metabolism process,NF-κB binding,etc.PI3K-Akt signaling pathway,AMPK signaling pathway,HIF-1 signaling pathway,etc.were involved in rutin treatment of spinal cord injury by KEGG pathway analysis;③Molecular docking experiments and molecular dynamics simulations show that rutin has good and stable binding with five core targets;④The results of in vivo experiments indicate that drug intervention with rutin after SCI can reduce the water content in the spinal cord,and reduce the production of inflammatory factors and oxidative stress factors.These results demonstrate that rutin has anti-inflammatory and anti-oxidative effects in the treatment of SCI through multiple targets and pathway.
network pharmacologyGEO differential gene chiprutinspinal cord injurymolecular dockingin vivo experiments