Cistanche deserticola Y. C. Ma is a traditional Chinese medicine with estrogen-like effects, which has a good development prospects, glycosides are the main active ingredients of its estrogen-like compounds. However, up to now, the hepatic metabolic process of the total glycosides (TGs) of C. deserticola has not been reported. In this study, Wistar rats were intragastric administrated with TGs (18.75 g · kg−1 · d−1 in crude drugs) to collect the hepatic portal vein (HPV) serum and bile; moreover, TGs solution (93.75 mg·mL−1) was added in liver homogenate. Ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical components of the samples. The results showed that, 69 components were detected in HPV serum, including 3 prototypes and 66 metabolites. In liver homogenate, 71 components were detected, comprising 7 prototypes and 64 metabolites. Moreover, 43 components were detected in bile, including 2 prototypes and 41 metabolites. Overall, 34 chemical components of TGs were identified to be involved in hepatic metabolism, its main metabolic pathways were revealed, including methoxylation, hydroxylation, glucuronidation, methylation and demethylation. This indicated that hepatic metabolism is a major metabolic pathway of TGs in rats. The identification of TGs prototype compounds and their metabolites is of great significance for further in-depth research and development of C. deserticola as medicinal food for treating menopausal symptoms.

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