Buzhong Yiqi decoction (BZYQD) is a traditional Chinese medicine prescription for treating neurogenic bladder (NB). However, the underlying pharmacological mechanism remains unclear. This study aims to clarify the related molecular mechanism. Molecular structure information and targets of core components of BZYQD were obtained from Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP) and SwissTargetPrediction databases. Genes involved in NB were obtained from Comparative Toxicogenomics Database, DisGeNet, GeneCards, and Online Mendelian Inheritance in Man databases. The hub targets of BZYQD in NB treatment were identified by protein–protein interaction (PPI) network analysis with STRING platform and analyzed by gene ontology analysis and the Kyoto Encyclopedia of Genes and Genomics pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the hub targets and the bioactive components of BZYQD. Subsequently, the neuroprotective and anti-inflammatory effects of main bioactive components of BZYQD were investigated with in vitro assays. A total of 131 candidate compounds and 925 predicted target genes were screened. PPI network analysis suggested that ESR1, EGFR, HSP90AA1, MAPK3, AKT1, and CASP3 were the hub targets. BZYQD treatment was associated with hypoxia inducible factor-1 (HIF-1) signaling pathway. Dehydroglyasperin C (DGC), N-cis-feruloyltyramine, shinpterocarpin (SHI), gancaonin M, and glyasperin B, as the main bioactive components of BZYQD, had good binding affinity with hub target proteins. DGC and SHI treatment could significantly inhibit the injury of neurons and inflammatory response of microglia stimulated by oxidized low-density lipoprotein (ox-LDL), respectively. In summary, BZYQD and its main bioactive components DGC and SHI show good potential to ameliorate the symptoms of NB.
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