Tittle Exploring the Mechanism of Resveratrol on Traumatic Brain Injury by Network Pharmacology and Molecular Docking

Abstract

[Background] Resveratrol is a polyphenol present abundantly in lots of traditional Chinese medicines, which has been shown to have beneficial effects on neurological diseases. However, the molecular mechanisms of resveratrol on traumatic brain injury have not been systematically studied yet. In this study, we elucidated the pharmacological mechanisms of resveratrol in treating traumatic brain injury by using a network pharmacology method. [Methods] The pharmacokinetics properties of resveratrol were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). The putative targets of resveratrol were obtained from TCMSP, BATMAN-TCM, SuperPred, PharmMapper, SwissTargetPrediction, DrugBank, and a literature search. The targets related to traumatic brain injury were obtained from TTD, DrugBank, CTD, GeneCards, OMIM, MalaCards, and a literature search. The STRING database and the Cytoscape 3.8.0 software were used to build the protein-protein interaction (PPI) network. The Metascape database was used to obtain the gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment information. Finally, The AutoDockTools 1.5.6 and PyMOL 2.4.0 software were employed for molecular docking analyses, and Discovery Studio 2020 was used for interaction analyses. [Results] A total of 165 overlapping targets involved in resveratrol intervention in traumatic brain injury were determined. The GO function analysis indicated that the targets are including the positive regulation of transferase activity, the positive regulation of cell migration, reactive oxygen species metabolism, the wound response, and so on. The KEGG pathway analysis identified the following enriched pathways: the AGE-RAGE signalling pathway, the FoxO signalling pathway, insulin resistance, complement and coagulation cascades, the HIF-1 signalling pathway, and so on. According to the PPI network analysis, INS, IGF1, TNF, TP53, ALB, IL6, SRC, STAT3, VEGFA, and MMP9 were identified as hub target genes, in which IL6, MMP9, INS, and SRC showed a good binding affinity with resveratrol in molecular docking. [Conclusions] Resveratrol may target multiple genes and multiple pathways to reduce brain damage after traumatic brain injury.