Therapeutic Effect and Mechanism of Da-Huang-Zhe-Chong Pills on Uterine Fibroids Using Liquid Chromatography Combined With Mass Spectrometry Metabolomics

Abstract

Da-Huang-Zhe-Chong Pills (DHZCPs) have demonstrated efficacy in treating uterine fibroids (UFs), but the mechanisms underlying their action remain unclear. In this study, untargeted serum metabolomic analysis was employed to investigate the therapeutic effects of DHZCP in a rat model of UFs utilizing advanced ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and pattern recognition. Histopathological examination through H&E staining revealed significant improvements in uterine morphology following DHZCP administration. The levels of four serum hormones, that is, estradiol (E₂), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (PROG), tended to shift toward normal in the DHZCP-treated group compared with the model group. Our metabolomic profiling identified 20 distinct endogenous metabolites that were differentially expressed between UF and normal rats, with DHZCP treatment significantly normalizing 16 of these metabolic markers. Comprehensive pathway analysis highlighted three major metabolic pathways affected by DHZCP intervention: tryptophan metabolism, riboflavin metabolism, and arginine-proline metabolism. Notably, spearman correlation analysis indicated that tryptophan, lysoPC (18:1/0:0), uric acid, and serotonin were strongly positively correlated with serum levels of both E₂ and PROG. Additionally, riboflavin, indoleacetic acid, and indole-3-propionic acid were positively correlated with E₂ levels. Our findings suggest that DHZCP may exert therapeutic effects primarily through the modulation of tryptophan and riboflavin metabolism, providing a solid foundation for its clinical application.