Exploring therapeutic targets for neuroinflammation in sepsis-associated encephalopathy: a combined network pharmacology and bioinformatics approach

Background Sepsis-associated encephalopathy (SAE) is a frequent but underrecognized complication of sepsis, yet no effective pharmacological interventions are currently available. Traditional Chinese medicine (TCM) offers a promising multi-component and multi-target strategy. Methods We used an integrative strategy combining network pharmacology, bioinformatics, and molecular modeling was employed to investigate a seven-herb TCM formula. Active compounds were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and disease-related genes were obtained from GSE135838. Overlapping targets were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses, and network topology analysis was performed to identify key hub genes and core compounds. Compound–target interactions were evaluated using molecular docking, molecular dynamics (MD) simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis. Results A total of 121 active compounds and 255 targets were identified, with 29 overlapping genes related to SAE. Five hub genes—amyloid precursor protein (APP), B-cell lymphoma 2 (BCL2), caspase-3 (CASP3), intercellular adhesion molecule 1 (ICAM1), and interleukin-6 (IL-6)—and five core compounds (quercetin, luteolin, kaempferol, β-sitosterol, and 7- O -methylisomucronulatol) were identified. Molecular docking revealed favorable compound–target interactions (binding energies: −5.7 to −9.1 kcal/mol). MD simulations confirmed stable APP–ligand complexes throughout the 100 ns simulation period. MM-PBSA analysis showed that β-sitosterol exhibited the strongest binding affinity toward APP (ΔGbind = −23.67 kcal/mol). Conclusion This study highlights the multi-target and multi-pathway therapeutic potential of a seven-herb TCM formula against SAE and identifies potential bioactive compounds and therapeutic targets for further investigation.