Nardosinone, a sesquiterpene peroxide, is one of the main active constituents of the ethnomedicine Nardostachyos Radix et Rhizoma, and it has many bioactivities, such as antiarrhythmia and cardioprotection. To elucidate its in vivo existence forms, its metabolism is first studied using mice. All urine and feces are collected during the six days of oral dosing of nardosinone, and blood is collected at one hour after the last dose. Besides, to validate some metabolites, a fast experiment is performed, in which nardosinone was orally administered and the subsequent one-hour urine is collected and immediately analyzed by UHPLC-Q-TOF-MS. In total, 76 new metabolites are identified in this study, including 39, 51, and 12 metabolites in urine, plasma, and feces, respectively. Nardosinone can be converted into nardosinone acid or its isomers. The metabolic reactions of nardosinone included hydroxylation, hydrogenation, dehydration, glucuronidation, sulfation, demethylation, and carboxylation. There are 56 and 20 metabolites with the structural skeleton of nardosinone and nardosinone acid, respectively. In total, 77 in vivo existence forms of nardosinone are found in mice. Nardosinone is mainly excreted in urine and is not detected in the feces. These findings will lay the foundation for further research of the in vivo effective forms of nardosinone and Nardostachyos Radix et Rhizoma.

Smilacis Glabrae Rhizoma is a traditional Chinese medicine commonly used for hyperuricemia. Engeletin, one of its major flavonoids, exhibits various pharmacological activities, but its in vivo uric acid-lowering activity and metabolic processes remain unclear. This study aims to elucidate the in vivo existence forms of engeletin and the pharmacological basis underlying its uric acid-lowering effects. The in vivo metabolites of engeletin were identified by using UHPLC-Q-TOF-MS. The xanthine oxidase inhibitory activity was investigated using in vitro enzymatic assays. The in vivo uric acid-lowering effect was evaluated in hyperuricemic mice. A total of 11, 34, 7, 6, and 5 compounds were detected in urine, feces, serum, liver, and kidney samples, respectively. After removing duplicates, 52 compounds were preliminarily identified as in vivo existence forms of engeletin. The main metabolic reaction types were glucuronidation, sulfation, and hydrolysis. Engeletin exhibited no xanthine oxidase inhibitory activity in vitro but possessed uric acid-lowering activity in vivo. Neoisoastilbin and naringenin were metabolites with both xanthine oxidase inhibitory activity and uric acid-lowering activity. The in vivo uric acid-lowering activity of engeletin may be attributable to its two metabolites rather than itself. This study elucidated the pharmacological basis of engeletin and laid the foundation for developing potential therapeutics for hyperuricemia.