Medicinal Plant Common Efficacy-based Strategy To Identify The Effect Of Luteolin On TBI By Targeting EGFR

Background: Numerous medicinal plants could promote the recovery of neurological function after traumatic brain injury(TBI).However,the common mechanism behind their common efficacy has not been elucidated.Purpose: By revealing the common mechanism based on the common efficacy of medicinal plants in treating TBI,we explore the potential compound and elucidate its therapeutic mechanism for TBI treatment.Methods:(1)Literature related to medicinal plants treating TBI was conducted.We identified active compounds of medicinal plants from the TCMSP Database.Their potential targets were identified through the TCMSP database and the Swiss Target Prediction database.TBI-related targets were predicted through the OMIM database and TTD database.Medicinal plants-candidate compounds network,candidate compoundscandidate targets network,protein-protein interaction(PPI)network of candidate targets,and PPI of overlapping targets were constructed and analyzed by Cytoscape.Autodock vina was used for molecular docking.Gene function analyses were used by the David database.(2)Based on the network pharmacology research strategy and molecular docking analysis,we screened epidermal growth factor receptor(EGFR)as hub-gene and luteolin as the most active compounds.Luteolin and EGFR inhibitors were given in the TBI mice,respectively.Neurological functional evaluation was performed by behavioral parameters and morphological staining.Astrocyte activation and glial scar formation were evaluated by immunofluorescence staining.Results: Firstly,16 medicinal plants were collected,including 209 unique compounds and 21 common compounds.131 targets were obtained based on the intersection of medicinal plants targets and TBI-related targets.Moreover,pathway enriched with the overlapping targets were mainly related to AGE/RAGE pathway,EGFR tyrosine kinase inhibitor resistance pathway.Based on network topology analysis,EGFR is the key protein in the overlapping target PPI network.Molecular docking analysis showed that luteolin had the strongest binding ability to EGFR.From the animal experiments,luteolin promoted the recovery of body weight and neurological function after TBI.Luteolin reduced activation level of astrocyte and EGFR expression in astrocytes.Glial scar expression was decreased and axon regrowth was upregulated in the luteolin-treated group.Conclusions:(1)The effective medicinal plants for treating TBI may play a therapeutic role through common components such as luteolin,baicalin,catechin,rhein,isorhamnetin and naringin,targeting common targets such as EGFR and PTGS2,and regulating common mechanisms such as AGE/RAGE pathway,EGFR tyrosine kinase inhibitor resistance,gastrin signal transduction pathway,BDNF signal pathway and VEGFAVEGFR2 signal pathway;(2)EGFR inhibitor can promote axonal regeneration and improve the prognosis after TBI by reducing astrocyte activation and glial scar formation;(3)Luteolin acts like EGFR inhibitor,reducing astrocyte activation and glial scar formation,and promoting axonal regeneration after TBI.