Pakistan journal of pharmaceutical sciences · 2026
Puerarin mitigates traumatic brain injury via ferroptosis-related targets and immune modulation: An integrated bioinformatics and experimental analysis.
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Zhao Zhiqiang, Li Fan, Cui Zhenfen, Guo Tiezhu
Аннотация
BACKGROUND: Ferroptosis is closely involved in the pathological process of traumatic brain injury (TBI), and Puerarin has potential neuroprotective activity.
OBJECTIVES: This study aims to investigate the main targets and underlying mechanisms of Puerarin against traumatic brain injury (TBI) from the perspective of ferroptosis.
METHODS: The GSE104687 dataset (194 TBI and 182 control samples) was obtained from Gene Expression Omnibus (GEO) and differentially expressed genes (DEGs) were identified using the R package limma. The ferroptosis-related genes (FRGs) were compiled from GeneCards and MSigDB and Puerarin-related targets were retrieved from PubChem, Similarity Ensemble Approach (SEA) and SwissTargetPrediction. Four key ferroptosis-related DEGs (FDTRDEGs) were obtained by intersecting DEGs with FRGs and Puerarin targets: NQO1, VCP, PML and RELA. Finally, a mouse TBI model was established to evaluate Puerarin's effects on brain injury, neurological deficits, brain water content and molecular changes across sham, TBI and TBI + Puerarin groups.
RESULTS: In the TBI model, Puerarin treatment reduced brain injury, inflammation, neurological deficits, and brain water content in TBI mice and reversed the TBI-induced expression changes of the four key genes at both mRNA and protein levels.
CONCLUSIONS: Puerarin may protect against TBI by targeting ferroptosis-related pathways, with core genes NQO1, VCP, PML and RELA playing key roles. It may also modulate immune cell infiltration through these targets, contributing to its therapeutic effects.
OBJECTIVES: This study aims to investigate the main targets and underlying mechanisms of Puerarin against traumatic brain injury (TBI) from the perspective of ferroptosis.
METHODS: The GSE104687 dataset (194 TBI and 182 control samples) was obtained from Gene Expression Omnibus (GEO) and differentially expressed genes (DEGs) were identified using the R package limma. The ferroptosis-related genes (FRGs) were compiled from GeneCards and MSigDB and Puerarin-related targets were retrieved from PubChem, Similarity Ensemble Approach (SEA) and SwissTargetPrediction. Four key ferroptosis-related DEGs (FDTRDEGs) were obtained by intersecting DEGs with FRGs and Puerarin targets: NQO1, VCP, PML and RELA. Finally, a mouse TBI model was established to evaluate Puerarin's effects on brain injury, neurological deficits, brain water content and molecular changes across sham, TBI and TBI + Puerarin groups.
RESULTS: In the TBI model, Puerarin treatment reduced brain injury, inflammation, neurological deficits, and brain water content in TBI mice and reversed the TBI-induced expression changes of the four key genes at both mRNA and protein levels.
CONCLUSIONS: Puerarin may protect against TBI by targeting ferroptosis-related pathways, with core genes NQO1, VCP, PML and RELA playing key roles. It may also modulate immune cell infiltration through these targets, contributing to its therapeutic effects.