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 C

ABSTRACT

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.