Bran stir-frying remodels Fructus Aurantii through flavonoid deglycosylation and limonoid reduction

Bran stir-frying (BS) is traditionally used to improve the properties of Fructus Aurantii (FA), but previous studies mainly focused on chemical changes or pharmacological differences, leaving global transformation pathways and functional consequences unclear. This study integrated in-depth analysis of molecular networking (IDAMN), metabolomics, mechanism validation, and functional validation to elucidate BS-FA processing mechanisms. Compared with conventional molecular networking, IDAMN can identify and remove 63.2% redundant nodes derived from other adduct, isotope, and in-source fragments. BS processing increased flavonoid aglycones while reducing flavonoid glycosides, limonoids, and phosphoglycerides. Mechanism validation indicated heat-assisted glycoside cleavage promoted aglycone formation, whereas limonoid reduction was associated with wheat bran adsorption. Functional validation demonstrated enhanced gastrointestinal motility of BS-FA compared with Raw-FA (47.1% vs 24.5% emptying rate at 200 μg/mL). Naringenin showed stronger activity than naringin, while limonin exhibited reduced effects at higher concentrations. Collectively, BS processing may improve FA quality by enriching efficacy-related flavonoid aglycones while reducing bitterness/irritation-related limonoids.