Objective To investigate the mechanism of Jianpi Yiqi Prescription for the treatment of traumatic brain injury (TBI) based on network pharmacology, molecular docking, and animal experiments. Methods (1) The active components and effect targets of Jianpi Yiqi Prescription were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, China National Knowledge Infrastructure and STRING databases. TBI⁃related targets were obtained from the GEO, GeneCards®, and OMIM® databases. The intersection targets were identified. A drug⁃active component⁃target network was constructed using Cytoscape software, and key active components were screened. A protein⁃protein interaction (PPI) network was constructed using the STRING database, and core targets were screened. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the intersection targets were performed using the DAVID database. Molecular docking validation was performed between the top 4 key active components (ranked by Degree value) and the core target proteins. (2) Thirty SD rats were randomly divided into blank control group (n=10) or modeling group (n=20). Rats in the blank control group were kept under normal feeding conditions without any intervention during experimetal period. The TBI model was established in the modeling group using the modified Feeney's free⁃fall impact method. Successfully modeled rats were randomly divided into model group (n=10) or drug intervention group (n=10). Rats in the drug intervention group received intragastric administration of Jianpi Yiqi Prescription, while rats in the model group and blank control group received intragastric administration of normal saline, once daily for 7 consecutive days. Neurological function was assessed using the modified Garcia JH score (mGarcia JH). Pathological changes in rats' brain tissue were observed using HE staining, and changes in Nissl bodies were observed using Nissl staining. The mRNA expressions of threonine protein kinase 1 (AKT1), interleukin (IL)⁃6, and tumor necrosis factor (TNF), and receptor for advanced glycation end product (RAGE) in rats' brain tissue were detected by RT⁃qPCR. The protein expressions of AKT, IL⁃6, and TNF⁃α in rats' brain tissue were detected by Western blot. Results (1) Jianpi Yiqi Prescription contained 72 active components, corresponding to 220 effect targets. There were 3455 TBI⁃related targets, yielding 148 intersection targets. Key active components of Jianpi Yiqi Prescription for treating TBI included quercetin and kaempferol, while core targets included AKT1, IL⁃6, TNF, etc. The intersection targets were mainly involved in biological processes such as response to lipopolysaccharide and response to hypoxia. They were enriched in cellular components including cytoplasm and extracellular space, and mitochondria, involved in molecular functions including enzyme binding and protein binding, and involved in signaling pathways including the advanced glycation end product (AGE)⁃RAGE signaling pathway, IL⁃17 signaling pathway, and p53 signaling pathway. Molecular docking indicated that the binding energies between the 4 key active components and the core target proteins were all ≤-5 kcal/mol. (2) Compared with the blank control group, the mGarcia JH score decreased in the model group. Compared with the model group, the mGarcia JH score elevated in the drug intervention group (P<0.05). HE staining results revealed obvious congestion and edema in the area surrounding the hematoma of the model group, with widespread hemorrhage, necrotic changes such as pyknosis and karyolysis of neuronal cells, and abundant reactive gliosis. Compared with the model group, pathological damage to brain tissue was significantly ameliorated in the drug intervention group. Nissl staining results interpreted that the number of Nissl⁃positive neurons significantly decreased in the model group compared with the blank control group, while it significantly increased in the drug intervention group compared with the model group. Compared with the blank control group, the mRNA and protein expressions of IL⁃6 and TNF⁃α were up⁃regulated, while the mRNA and protein expressions of AKT were down⁃regulated in the brain tissue of the model group (P<0.05). Compared with the model group, the mRNA and protein expressions of IL⁃6 and TNF⁃α in the brain tissue of the drug intervention group were down⁃regulated (P<0.05). Compared with the blank control group, the mRNA expression of RAGE in the brain tissue of the model group was up⁃regulated (P<0.05). Compared with the model group, the mRNA expression of RAGE in the brain tissue of the drug intervention group was down⁃regulated (P<0.05). Conclusion Jianpi Yiqi Prescription may exert its therapeutic effect on TBI by regulating inflammatory response, oxidative stress, and cell apoptosis.

无