Exploring Key Lipid Molecules of Primary Dysmenorrhea for Elucidating the Biological Effects of Danggui Shaoyao San Using <scp>UPLC</scp> ‐Q‐ <scp>TOF</scp> ‐ <scp>MS</scp> ‐Based Lipidomics

Primary dysmenorrhea (PD) has always been a significant clinical challenge affecting women's health. Traditional Chinese medicine (TCM) has attracted considerable research interest owing to its advantages of multiple target and multiple pathway. This study employed urinary lipidomics technology combined with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-O-TOF-MS) to systematically elucidate the preventive mechanisms and therapeutic targets of Danggui Shaoyao San (DSS) in a PD rat model. A total of 34 lipid biomarkers representing the dysregulated lipid metabolism in PD were preliminarily identified. Except for 3alpha-hydroxy-5beta-chola-7,9(11)-dien-24-oic acid and 16-oxoandrostenediol, all 32 lipids had high diagnostic significance. And then, the metabolic alterations related to DSS intervention through the regulation of lipid biomarkers and related pathways were discovered. Among the differentially expressed lipids, 29 lipid biomarkers were significantly restored by DSS administration. Through the pathway enrichment analysis, two key perturbation pathways related to DSS therapy were found, including arachidonic acid metabolism, and primary bile acid biosynthesis, which had the potential to become new therapeutic targets for treating PD. These investigations demonstrated that DSS may have a significant efficacy on the progression of PD by multi-target regulation of lipid biomarkers and lipidomics-guided biochemical pathways, providing a scientific foundation for its clinical application.