Taxonomy-Driven Core Scaffold Expansion Strategy for Comprehensive Profiling of Secondary and In Vivo Metabolites of Raphani Semen and Study on Promoting Gastrointestinal Motility

Raphani Semen (RS) has two different application forms in the Chinese Pharmacopoeia (ChP): raw RS and stir-fried RS. However, the compounds of raw and stir-fried RS decoctions, in vivo metabolic pathways, and the effects on promoting gastrointestinal motility remain completely unclear. To address this, a Taxonomy-Driven Core Scaffold Expansion (TDCSE) strategy was developed to track compounds of raw and stir-fried RS decoctions and subsequent in vivo metabolic pathways. Then, a zebrafish model was used to evaluate the effect of raw and stir-fried RS decoctions on promoting gastrointestinal motility. Finally, through network pharmacology and molecular docking techniques, the potential targets and pathways of absorbed compounds were predicted. The results indicated that 26 compounds were detected in the stir-fried RS decoction. In addition to these 26 compounds, another 50 compounds were detected in the raw RS decoction. Moreover, a total of 123 metabolites (including prototypes) were detected after removing the duplications. A total of 18, 71, 59, and 4 metabolites were discovered in plasma, urine, feces, and liver tissue, respectively. Evaluation in a zebrafish model demonstrated that both raw RS and stir-fried RS decoctions possessed the effect of promoting gastrointestinal motility compared with the model group. The promoting gastrointestinal motility potential targets, PTGS2, TNF, PARP1, MTOR, etc., and the IL-17 pathway were predicted. Collectively, this study clarified the differences in compounds and in vivo metabolites of raw and stir-fried RS decoctions. It provided a reference for further investigation into the effect of promoting gastrointestinal motility of RS.