College of Pharmacy, Binzhou Medical University, Yantai 264003, China.
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, China.
Molecules. 2022 Oct 26;27(21):7282. doi: 10.3390/molecules27217282.
Naringenin (5,7,4'-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named "ion induction and deduction" was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple "net-hubs" and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.
柚皮素（5,7,4'-三羟基黄烷酮）属于黄烷酮子类，具有抗氧化、抗癌、抗炎和抗糖尿病等有益作用。药物代谢在药物发现和临床安全中起着至关重要的作用。然而，由于代谢样品中存在大量内源性物质，药物代谢物的鉴定和有效表征具有一定的难度。本研究采用超高效液相色谱（UHPLC）结合高分辨质谱，获得了血浆（经三种方法处理）、尿液、粪便、肝组织和肝微粒体样品的质谱信息。此外，提出了一种名为“离子诱导与推断”的新型分析策略，用于系统筛选和鉴定体内和体外柚皮素的代谢物。该分析策略通过建立多个“网络枢纽”和推断碎片行为来完成。最终，从大鼠血浆、尿液、粪便、肝组织和肝微粒体样品中检测和鉴定了 78 种柚皮素代谢物，其中 67 种在体内检测到，13 种在体外检测到。柚皮素主要经历了葡萄糖醛酸化、硫酸化、氧化、甲基化、环裂解以及转化为酚酸及其复合反应。本研究为从复杂样品中提取目标信息提供了重要帮助，并为其他药理学和毒理学研究奠定了基础。
