目的 研究胡芦巴多糖（FS60）与总姜黄素（Curcuminoids）自组装纳米聚集体对其主要活性成分姜黄素（curcumin，Cur）体内代谢的影响。方法 随机将SD雄性大鼠分为空白组、总姜黄素组、FS60-总姜黄素Ⅰ组和FS60-总姜黄素Ⅱ组，其中FS60-总姜黄素Ⅱ组ig FS60（3.44 g/kg），其余组给予等体积纯水。干预7 d后，各组以100 mg/kg Cur剂量ig相应药物，空白组给予等体积纯水。收集血浆、肝脏、尿液和粪便样品并进行预处理，采用超高效液相色谱串联四级杆-静电场轨道阱高分辨质谱（UPLC-Q-Orbitrap HRMS）技术，分别在正、负离子模式下对各组Cur原型及其代谢产物进行鉴定和对比分析。结果 共检测出29种Cur代谢产物，其中总姜黄素组24种，FS60-总姜黄素Ⅰ组27种，FS60-总姜黄素Ⅱ组29种。组间对比分析可知，胡芦巴多糖FS60通过包裹总姜黄素形成自组装FS60-总姜黄素聚集体增加了可检出的体内Cur代谢产物种类以及促进Cur代谢产物体循环。长时间摄入FS60-总姜黄素聚集体可能由于FS60的持续干预可进一步提高Cur的吸收与代谢。结论 初步明确了胡芦巴多糖FS60对Cur体内代谢产物种类及其代谢转化的影响，为进一步明确胡芦巴多糖递送姜黄素的药效学意义提供研究基础。

Objective To study the effects of self-assembled nanoaggregates formed by fenugreek polysaccharide (FS60) and curcuminoids on the metabolism of curcumin (Cur) in vivo. Methods SD male rats were randomly divided into blank group, Curcuminoids group, FS60-curcuminoids Ⅰ group and FS60-curcuminoids Ⅱ group. FS60-curcuminoids Ⅱ group was given FS60 (3.44g/kg) via gavage. The other groups were given equal volume pure water. After 7 d of intervention, 100 mg/kg Cur were given to each treatment group by gavage, and the blank group was given equal volume pure water. Plasma, liver, urine and fecal samples were collected and pretreated. The Cur prototypes and their metabolites were analyzed and identified in positive and negative ion modes by ultra performance liquid chromatography coupled with hybrid quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). Results A total of 29 species of Cur metabolites were detected, including 24 species in Curcuminoids group, 27 species in FS60-curcuminoids Ⅰ group and 29 species in FS60-curcuminoids Ⅱ group. The comparison between groups showed that FS60 encapsulated Curcuminoids to form self-assembled FS60-curcuminoids aggregates, which increased the types of Cur metabolites that could be detected in vivo and promoted the systemic circulation of them. Long-term intake of FS60-curcuminoids aggregates may further improve the absorption and metabolism of Cur due to the continuous intervention of FS60. Conclusion The effects of fenugreek polysaccharide FS60 on the types of metabolites and their metabolic transformation in Cur were clarified, which provided the research basis for further clarifying the pharmacodynamic significance of delivery of Cur by fenugreek polysaccharide.

R284.1

国家重点研发计划-中医药现代化专项（2023YFC3504101）;国家自然科学基金面上项目（82073994）;成都中医药大学杏林学者学科人才科研提升计划（QJJJ2021002）