Xuebijing Alleviates Microglial Activation after Traumatic Brain Injury via Regulation of NF-κB Pathway: Network Pharmacology and Experimental Validation.

Abstract

Objective: Xuebijing (XBJ) injection, a traditional Chinese medicine (TCM) widely used in China for treating sepsis and multiple organ dysfunction, has shown neuroprotective effects in traumatic brain injury (TBI). However, the mechanisms underlying these effects remain unclear. This study aims to elucidate the neuroprotective and pharmacological molecular mechanisms of XBJ and its active monomer, Hydroxy-safflor yellow A (HSYA), in treating TBI through network pharmacology and experimental validation.

Methods: Potential therapeutic targets for TBI were collected from TCMSP, TTD, OMIM, and GeneCards databases. Active compounds and targets of XBJ injection were obtained from TCMSP. The STRING database and Cytoscape software constructed a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database and visualized with Bioinformatics tools. Neuroprotective effects of XBJ were verified in vitro using BV2 and primary microglia cells stimulated by Lipopolysaccharide (LPS). Additionally, a TBI mice model was used to identify microglial activation in vivo.

Results: A total of 161 common targets related to TBI were identified. Network pharmacological analysis suggested that XBJ targets proteins involved in inflammation. In vitro results showed that XBJ and HSYA inhibited LPS-induced microglial activation via the NF-κB pathway. Furthermore, XBJ was found to inhibit microglial activation in TBI mice.

Conclusion: These findings indicate that XBJ and HSYA may treat TBI by repressing microglial activation through the NF-κB pathway. Our study provides valuable evidence supporting XBJ as an effective therapy for TBI.