Based on UHPLC–Q‐TOF–MS and bioinformatics strategies, the potential allergens and mechanisms of allergic reactions caused by Danshen injection were explored

The aim is to investigate the potential allergens and mechanisms underlying allergic-like reactions induced by Danshen injection (DSI). Utilizing ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), metabolomics, and bioinformatics, we identified the key allergens, targets, and metabolic pathways involved in DSI-induced allergic-like reactions, validating binding efficiency through molecular docking and molecular dynamics. A total of 45 compounds were identified within DSI, with 24 compounds exhibiting strong binding activity to the MrgprX2 activation site. DSI was found to cause changes in 89 endogenous metabolites, including arachidonic acid, prostaglandins, and leukotrienes, primarily affecting pathways such as phenylalanine metabolism and arachidonic acid metabolism. The key allergens identified were Cryptotanshinone, Miltipolone, Neocryptotanshinone, Salvianolic acid B, and Isosalvianolic acid C, which primarily trigger allergic-like reactions by regulating upstream signaling targets such as ALOX5, PTGS1, PPARD, and LTB4R. Validation confirmed the high binding affinity and stability between key allergens and targets. These findings indicate that the allergic components in DSI primarily induce allergic-like reactions by modulating the aforementioned signaling targets, activating the AA metabolic pathway, promoting mast cell degranulation, and releasing downstream endogenous inflammatory mediators, subsequently eliciting allergic-like reactions.