Analysis of the mechanism of celastrol against oxaliplatin-induced peripheral neuropathy on network pharmacology
Objective To investigate the effects and mechanisms of celastrol on oxaliplatin-induced peripheral neurop-athy(OIPN)by experiments and network pharmacology.Methods Oxaliplatin and celastrol were administered to rats and colon cancer cells to investigate the effect of celastrol on OIPN.The targets of celastrol were collected using TCMSP,Swis-sTargetPrediction and PharmMapper databases,and the targets of oxaliplatin-induced peripheral neuropathy were obtained from GeneCards and OMIM databases.Both of the intersected targets were taken and the network diagram of celastrol-targets-OIPN was constructed by Cytoscape software.The protein-protein interaction(PPI)network diagram of the targets was constructed using STRING database.DAVID database was used for GO functional enrichment analysis and KEGG pathway enrichment analysis of those intersection targets,and MOE software was used for molecular docking verification of core tar-gets.Results Celastrol could significantly improve the mechanical and cold stimulation pain sensitivity symptoms induced by oxaliplatin in rats,reduce the pathological injury of dorsal root ganglion neurons and sciatic nerve,and do no harm on the killing effect of oxaliplatin on colon cancer cells in vitro.Network pharmacological analysis obtained 309 targets of celastrol,1 318 targets of OIPN and 80 targets of their intersection.The core targets such as HSP90AA1,CASP3 and PTGS2 were ob-tained by PPI interaction network analysis.GO enrichment analysis obtained 193 items and KEGG results showed that celas-trol might alleviate OIPN by regulating IL-17 signaling pathway and PI3K/Akt signaling pathway.The molecular docking re-sults further indicated that celastrol had good binding ability with core targets CASP3 and PTGS2.Conclusion Celastrol could ameliorate oxaliplatin-induced peripheral neuropathy,with network pharmacology revealing that the mechanism might involve multi-targets and multi-pathways regulation.
CelastrolOxaliplatinPeripheral neuropathyNetwork pharmacologyMolecular dockingEffect and mech-anism
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