College of Pharmacy, Binzhou Medical University, Yantai 264003, China.
College of Life Sciences, Shandong Agricultural University, Taian 271018, China.
Molecules. 2023 Jul 2;28(13):5168. doi: 10.3390/molecules28135168.
Xanthohumol (XN), a natural prenylated flavonoid extracted and isolated from the hop plant (), possesses diverse pharmacological activities. Although the metabolites of XN have been investigated in the previous study, a comprehensive metabolic profile has been insufficient in vivo or in vitro until now. The current study was aimed at systematically elucidating the metabolic pathways of XN after oral administration to rats. Herein, a UHPLC-Q-Exactive Orbitrap MS was adopted for the potential metabolites detection. A stepwise targeted matching strategy for the overall identification of XN metabolites was proposed. A metabolic net (53 metabolites included) on XN in vivo and in vitro, as well as the metabolic profile investigation, were designed, preferably characterizing XN metabolites in rat plasma, urine, liver, liver microsomes, and feces. On the basis of a stepwise targeted matching strategy, the net showed that major in vivo metabolic pathways of XN in rats include glucuronidation, sulfation, methylation, demethylation, hydrogenation, dehydrogenation, hydroxylation, and so on. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of prenylated flavonoids and lay the foundation for further toxicity and safety studies.
黄腐酚（XN）是一种从啤酒花植物中提取和分离得到的天然类异戊二烯黄酮，具有多种药理活性。尽管之前的研究已经研究了 XN 的代谢物，但直到现在，在体内或体外还没有全面的代谢物谱。本研究旨在系统阐明 XN 在大鼠口服后的代谢途径。在此，采用 UHPLC-Q-Exactive Orbitrap MS 进行潜在代谢产物的检测。提出了一种逐步靶向匹配策略，用于全面鉴定 XN 代谢物。设计了 XN 在体内和体外的代谢网络（包括 53 种代谢物）和代谢谱研究，优选表征了大鼠血浆、尿液、肝脏、肝微粒体和粪便中的 XN 代谢物。基于逐步靶向匹配策略，该网络表明 XN 在大鼠体内的主要代谢途径包括葡萄糖醛酸化、硫酸化、甲基化、去甲基化、氢化、脱氢、羟化等。本研究提出的代谢途径将为进一步的类异戊二烯黄酮药物研究提供重要数据，并为进一步的毒性和安全性研究奠定基础。
