目的 研究瓜蒌Trichosanthis Frucutus、瓜蒌皮Trichosanthis Pericarpium、瓜蒌子Trichosanthis Semen提取液在大鼠体内的代谢特征异同。方法 采用超高效液相色谱-线性离子肼-静电轨道肼串联质谱（UHPLC-LTQ-Orbitrap-MS）采集瓜蒌、瓜蒌皮及瓜蒌子提取液及大鼠ig各提取液后的血浆、胆汁、尿液、粪便的多级质谱信息，利用质量亏损过滤技术进行代谢产物鉴定及代谢途径分析。结果 在ig瓜蒌、瓜蒌皮和瓜蒌子提取液的大鼠体内分别鉴定到37、38、31种原型成分，其中，ig不同提取液的大鼠体内均鉴定到槲皮素、木犀草素、柚皮素、葫芦素D、腺苷、苯丙氨酸等，而芦丁、山柰酚、葫芦素B等仅在ig瓜蒌、瓜蒌皮提取液的大鼠体内被鉴定到。对共同鉴定到的芹菜素、橘红素、异槲皮苷、槲皮素和葫芦素D进行进一步的代谢产物鉴定，涉及的相关代谢产物有36种，主要代谢途径包括甲基化、羟基化、葡萄糖醛酸化、硫酸化等。值得注意的是，虽然代谢产物的数量和种类几近相同，但在生物样品中的分布却有差异。结论 系统地鉴定了瓜蒌、瓜蒌皮、瓜蒌子的成分及在大鼠体内的原型成分，并对芹菜素、橘红素、异槲皮苷、槲皮素和葫芦素D体内的代谢产物及代谢过程进行分析，阐明了三者的多元成分差异及其体内代谢特征，为进一步探讨其药动学行为及药效物质基础差异提供了参考，为瓜蒌资源的充分利用与临床合理用药提供了思路。

Objective To investigate the similarities and differences in metabolic characteristics of Gualou (Trichosanthis Fructus), Gualoupi (Trichosanthis Pericarpium), and Gualouzi (Trichosanthis Semen) extracts in rats after oral administration. Methods The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was applied to collect multi-level mass spectrometry fragment information of Trichosanthis Fructus, Trichosanthis Pericarpium, and Trichosanthis Semen. After the administration, plasma, bile, urine, and feces were qualitatively analyzed and the metabolites were identified by mass defect filter (MDF). Results A total of 38, 39, and 33 prototype components were identified in rats with different extract solutions of Trichosanthis Fructus, Trichosanthis Pericarpium, and Trichosanthis Semen, respectively. Quercetin, luteolin, naringin, cucurbitacin D, adenosine, and phenylalanine were identified jointly in rats with different extract solutions. However, rutin, kaempferol and cucurbitacin B were only identified in rats that were intragastric with Trichosanthis Fructus and Trichosanthis Pericarpium extract. In addition, further metabolites were identified for apigenin, tangerine, isoquercetin, quercetin and cucurbitacin D, and 36 related metabolites were involved. The in vivo main metabolic pathways included methylation, hydroxylation, gluconalylation, sulfation. It was worth noting that although the number and types of metabolites were almost the similar, the distribution in biological samples was different. Conclusion This study systematically identified the components and the metabolites information of Trichosanthis Fructus, Trichosanthis Pericarpium and Trichosanthis Semen and clarified their multiple component differences and metabolic characteristics in vivo. This study provided a reference for further study of pharmacokinetic behavior and pharmacodynamic material basis differences, and provided ideas for the full utilization of Trichosanthis Fructus resources and rational clinical drug use.

R284.1

国家自然科学基金资助项目(82104348);国家自然科学基金资助项目(82274404);江苏省自然科学基金资助项目(BK20210694,BK20201403);江苏省科研与实践创新计划项目(SJCX22_0801,SJCX22_0855)