A step‐by‐step progressive strategy exploring whole metabolic profiles in vivo for <i>Polygalae Radix</i> with/without <i>licorice</i>

The 85 polygala metabolites were qualitatively analyzed in plasma, brain, colon, and stomach contents. The 11 types of relatively large metabolites and 8 types of ACAs were quantitatively monitored. Among them, nine types of relatively large metabolites were assessed through PK studies. In targeted network pharmacology, it highlighted the significance of small molecular metabolites, including ACAs et al, which were frequently overlooked. LP may play a more key role mainly through neural active ligand-receptor interaction, AD, and pertussis pathways. These findings have outlined a step-by-step strategy for in-depth research in vivo, laying a foundation for further verification of biological function.