Uncovering the therapeutic efficacy and mechanisms of Quercetin on traumatic brain injury animals: a meta-analysis and network pharmacology analysis

Quercetin, a flavonoid and natural antioxidant derived from fruits and vegetables, has shown promising results in the improvement of traumatic brain injury (TBI). This study aims to elucidate the therapeutic role and potential mechanisms of quercetin in TBI through systematic evaluations and network pharmacology approaches. First, the meta-analysis was conducted via Review Manager 5.4 software. The meta-analysis results confirmed that quercetin could improve TBI, primarily by inhibiting inflammation, oxidative stress, and apoptosis. Subsequently, targets related to quercetin and those related to TBI were extracted from drug-related databases and disease-related databases, respectively. We found that the potential mechanism by which quercetin treats TBI is largely associated with ferroptosis, as indicated by functional analysis. Based on this, we identified 29 ferroptosis-related genes (FRGs) associated with quercetin and TBI, and then performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the DAVID database. The functional enrichment results revealed that these FRGs mainly involve the HIF-1 signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. Subsequently, we constructed a PPI network and identified the top 10 targets-HIF1A, IL6, JUN, TP53, IL1B, PTGS2, PPARG, EGFR, IFNG, and GSK3B-as hub targets. Meanwhile, molecular docking results further demonstrated that quercetin could stably bind to the top 10 hub targets. In conclusion, the above results elucidated that quercetin could effectively attenuates TBI by inhibiting inflammation, oxidative stress, and apoptosis. Notably, quercetin may also target these hub targets to regulate ferroptosis and improve TBI.