Uncovering the effects and mechanism of Danggui Shaoyao San intervention on primary dysmenorrhea by serum metabolomics approach.

• The efficacy of Danggui Shaoyao San in treating primary dysmenorrhea rats was observed. • A total of 23 biomarkers related to metabolic abnormalities in primary dysmenorrhea rats were revealed. • The key metabolic mechanism of Danggui Shaoyao San on the amelioration of primary dysmenorrhea was firstly investigated. Danggui Shaoyao San (DSS) is a well-known prescription for relieving primary dysmenorrhea (PD) of women in China. However, its pharmacological mechanism has not been thoroughly uncovered. Here, an integrative UPLC-Q-TOF-MS-based serum metabolomics approach coupled with multivariate data analysis has been proposed to investigate the effects and mechanism of DSS on estradiol benzoate and oxytocin-induced PD rats. 31 potential biomarkers of PD were screened and identified, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, and the occurrence of PD could destroy biological homeostasis in vivo by monitoring these pathways. After DSS treatment, 18 identified different metabolites were restored to the nomal state in varying degrees and could be potential biomarkers contributing to the treatment of DSS. These findings implyed that DSS exhibited a therapeutic effect on PD rats through regulating multiple abnormal pathways. Of note, this study discovered some potential biomarkers related to PD for the first time, such as L-tyrosine, glycocholic acid, citric acid, palmitoylcarnitine, cholesterol. It preliminarily proved the pathophysiology of PD and action mechanisms of DSS on PD, and provided a novel insight into the effectiveness of DSS on PD. [ABSTRACT FROM AUTHOR]