ABSTRACT Preeclampsia (PE) is a severe hypertensive disorder of pregnancy involving complex metabolic disturbances. This study aimed to elucidate PE's pathogenesis and aspirin's preventive mechanism using metabolomics and network pharmacology. The untargeted urinary metabolomics via ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) were performed on healthy pregnant women ( n = 11), PE patients ( n = 9), and potential PE patients with aspirin intervention ( n = 12). Multivariate analysis identified 162 differential metabolites. The PE group exhibited a distinct metabolic profile characterized by dysregulation in tryptophan, purine, arachidonic acid, and quinone pathways, contributing to increased oxidative stress, vasoconstriction, platelet aggregation, and inflammation. Notably, aspirin intervention reversed the levels of 28 key metabolites. Its primary preventive mechanism was associated with the targeted modulation of tryptophan metabolism and one‐carbon pool by folate, which appeared to inhibit the serotonin synthesis pathway and improve endothelial function. Importantly, both metabolomics and network pharmacology identified the one‐carbon metabolic and tryptophan metabolism pathways as key preventive targets for PE, corroborating their role in aspirin's mechanism. In conclusion, this study revealed a “metabolic network imbalance” in PE and confirmed that aspirin conferred specific protection to metabolism. These findings offered new insights for multitarget prevention strategies for PE and the development of diagnostic systems for metabolic biomarkers.
Yutao et al. (2025) studied this question.