Characterization of diterpene metabolism in rats with ingestion of seed products from Euphorbia lathyris L. (Semen Euphorbiae and Semen Euphorbiae Pulveratum) using UHPLC-Q-Exactive MS

Previous pharmacological studies have indicated that diterpenoids are the primary effective chemical cluster in the seeds of Euphorbia lathyris L. The seed products are used in traditional Chinese medicine in the forms of Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP). However, the metabolism of the plant's diterpenoids has not been well elucidated, which means that the in vivo metabolite products have not been identified. The current study screened the physiological metabolites of six diterpenes Euphorbia factor L₁ (L1), L₂ (L2), L₃ (L3), L_7a (L7a), L_7b (L7b), and L₈ (L8)] in feces and urine of rats after oral administration of SE and SEP using UHPLC-Q-Exactive MS. A total of 22 metabolites were detected in feces and 8 in urine, indicating that the major elimination route of diterpenoids is via the colon. Hydrolysis, methylation, and glucuronidation served as the primary metabolic pathways of these diterpenoids. In sum, this study contributed to the elucidation of new metabolites and metabolic pathways of SE and SEP, and the new chemical identities can be used to guide further pharmacokinetic studies.