Untargeted metabolomics reveals the synergistic mechanisms of Yuanhu Zhitong oral liquid in the treatment of primary dysmenorrhea

Primary dysmenorrhea is a prevalent gynecological disorder that severely affects the quality of life in women. Yuanhu Zhitong oral liquid (YZOL) is a standardized herbal preparation frequently used in clinical practice and is a promising alternative therapy for primary dysmenorrhea. The findings of previous studies show that YZOL exhibits significant analgesic and spasmolytic effects, however, the involved mechanism remains unclear. Herein, we performed an untargeted plasma metabolomic analysis on a mouse model of oxytocin-induced primary dysmenorrhea to investigate the underlying mechanism of YZOL. We used multivariate and pathway-driven analyses to uncover the treatment targets linked with YZOL therapy and verified the possible mechanisms through biochemical assays. Therefore, we identified 47 plasma biomarkers primarily associated with sphingolipid metabolism, amino acid metabolism, arachidonic acid metabolism, and biosynthesis of steroid hormone as well as primary bile acid. We established that the analgesic effect of YZOL on primary dysmenorrhea relies on multiple constituents that act on multiple targets in multiple pathways. Our correlation analysis showed significant correlations between the biomarkers and biochemical indicators, which is of considerable significance in elucidating the YZOL mechanisms. Moreover, we identified some novel prospective biomarkers linked to primary dysmenorrhea, including bile acids. Collectively, these data provide new insights into the mechanism of YZOL and provide evidence for the analgesic effect of YZOL in the treatment of primary dysmenorrhea.