Unraveling the Bioactive Compounds and Multi-Target Mechanisms of the Fructus Aurantii Immaturus-Bambusae Caulis in Taeniam Herb Pair Against Chronic Gastritis: Integrating Identification of Absorbed Constituents, Targeted Network Pharmacology, and Computational Validation.

Chronic gastritis is a prevalent global health concern, and there is growing interest in functional foods and nutraceuticals derived from traditional herbs as complementary approaches for gastrointestinal health management. The Fructus Aurantii Immaturus-Bambusae Caulis in Taeniam (FAI-BCT) herb pair exhibits health-promoting effects against chronic gastritis, but the underlying molecular mechanisms, particularly of its bioactive constituents, remain unclear. We established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) method to identify the blood-absorbed constituents and metabolites of FAI-BCT in rat plasma. Combined with GEO database mining and targeted network pharmacology, molecular docking and molecular dynamics simulations were further performed to explore its anti-gastritis mechanisms. 27 prototype components and 13 metabolites were identified or preliminarily characterized in plasma. Targeted network pharmacology identified 3',4',5,7-tetramethoxyflavone, 5'-methoxynobiletin (M5), naringenin, hesperetin, p-coumaric acid, ferulic acid, and nobiletin as key bioactive compounds. Core therapeutic targets included epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), B-cell lymphoma 2 (BCL2), matrix metalloproteinase-9 (MMP9), protein kinase B-α (AKT1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the PI3K-Akt signaling pathway as a key mechanism regulated by these compounds. Molecular docking verified strong binding affinities, and molecular dynamics simulations validated stable complex formations. This study elucidates the multi-target mechanisms of FAI-BCT in preventing and managing chronic gastritis, emphasizing the role of its highly bioavailable bioactive constituents. The findings provide robust evidence supporting FAI-BCT's potential application in functional foods or nutraceuticals for chronic gastritis and underscore the importance of bioavailability-focused research on traditional Chinese medicine (TCM) constituents.