Mechanism of neohesperidin in treatment of traumatic brain injury based on network pharmacology,molecular docking technique and animal experiments
Objective To study the effect of neohesperidin on traumatic brain injury in rats and explore its potential mechanism.Methods To obtain relevant targets of drugs and diseases by TCMSP,PharmMapper,OMIM,GeneCards and other databases and supplemented with literature.Construct the target PPI network between neohesperidin therapy and traumatic brain injury disease through STRING database.GO function and KEGG enrichment were analyzed based on the DAVID database,and the possible docking results of neohesperidin with key target proteins were simulated by Autodock Vina software.The model of traumatic brain injury in SD rats was established by Feeney's method,and the modified neurological impairment severity score(mNSS)was performed after the model.The pathological changes of neurons were observed by Nishi staining,the apoptosis of neurons was observed by TUNEL staining,and the expression levels of inflammatory factors IL-6,IL-1β,and TNF-α were measured by ELISA.The mRNA expression levels of VEGF,SRC,and Akt1 were detected by qRT-PCR.Results A total of 85 drug-disease intersection targets were obtained,and 10 core targets were screened,including MMP9,EGFR,MAPK8,IL-6,SRC,TNF,Akt1,etc.KEGG pathway analysis showed that the key targets may focus on the VEGF signaling pathway,TNF signaling pathway,Rap1 signaling pathway and other signaling pathways.Neohesperidin has a good affinity with the core targets MMP9,EGFR,MAPK8,IL-6,TNF,Akt1,etc.Animal experiments showed that neohesperidin treatment improved nerve function,reduced nerve cell injury and inhibited apoptosis(P<0.05),and neohesperidin treatment significantly decreased the expression levels of inflammatory factors IL-6,IL-1β and TNF-α in rat brain tissue(P<0.05).The mRNA expression levels of VEGF,SRC,and Akt1 were significantly up-regulated(P<0.05).Conclusion Neohesperidin may act on MAPK8,IL-6,SRC,TNF,Akt1,and other core targets,and play a role in the treatment of traumatic brain injury through multiple signaling pathways such as VEGF signaling pathway and TNF pathway,which has the characteristics of multi-target and multi-pathway.
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