目的 采用体外共孵育法考察早发性卵巢功能不全（premature ovarian insufficiency，POI）大鼠肠道菌群介导的菟丝子-枸杞子（Semen Cuscutae-Fructus Lycii，SC-FL）药对代谢转化规律。方法 将SC-FL及其13种单体成分分别与POI大鼠肠道菌群离体共孵育，并进行UPLC-Q-TOF-MS定性分析。结果 从SC-FL共孵育样品中共表征出85种化合物，包括芦丁等61种原型成分，甲基金丝桃苷等13种代谢产物，异鼠李素等11种同时以原型存在且可由其他成分经菌群代谢后产生的成分。金丝桃苷孵育样品中表征出5种代谢产物；芦丁孵育样品中表征出7种代谢产物；槲皮苷孵育样品中表征出6种代谢产物；紫云英苷孵育样品中表征出7种代谢产物；异槲皮苷孵育样品中表征出5种代谢产物；槲皮素孵育样品中表征出7种代谢产物；异鼠李素孵育样品中表征出4种代谢产物；山柰酚孵育样品中表征出5种代谢产物；芹菜素孵育样品中表征出4种代谢产物；绿原酸孵育样品中表征出9种代谢产物；阿魏酸孵育样品中表征出3种代谢产物；东莨菪苷孵育样品中表征出4种代谢产物；东莨菪内酯孵育样品中表征出3种代谢产物。结论 POI大鼠肠道菌群介导的代谢转化反应主要为水解、还原加氢、羟基化反应等I相代谢反应和甲基化反应等II相代谢反应，将各成分代谢情况进行反向溯源分析发现，异鼠李素、槲皮素、山柰酚和芹菜素在POI大鼠肠道菌群中存在相互代谢转化。为阐明SC-FL在POI状态下的药效物质基础及作用机制提供了重要依据，也为后续基于肠道菌群调控的SC-FL药效优化研究奠定了基础。

Objective The in vitro co-incubation method was employed to investigate the metabolic transformation regularity of Semen Cuscutae-Fructus Lycii (SC-FL) mediated by gut microbiota in premature ovarian insufficiency (POI) rats. Methods SC-FL and its thirteen monomer components were co-incubated with gut microbial communities from POI rats in vitro, followed by UPLC-Q-TOF-MS for qualitative analysis. Results A total of 85 compounds were characterized from the SC-FL co-incubated samples, including 61 prototypical components (e.g., rutin), 13 metabolites (e.g., methyl hyperoside), and 11 kinds of components that exist in the prototype at the same time and can be metabolized by other components, (e.g., isorhamnetin). Hyperoside was characterized by five metabolites, rutin by seven, quercitrin by six, astragalin by seven, isoquercitrin by five, quercetin by seven, isorhamnetin by four, kaempferol by five, apigenin by four, chlorogenic acid by nine, ferulic acid by three, scopoline by four, and scopoletin lactone by three. Conclusion The metabolic transformation reactions mediated by the intestinal microbiota in POI rats mainly include Phase I metabolic reactions such as hydrolysis, reduction-hydrogenation, and hydroxylation reactions, and Phase II metabolic reactions such as methylation reactions. Reverse traceability analysis of the metabolic conditions of each component revealed that isorhamnetin, quercetin, kaempferol and apigenin were mutually metabolically transformed in the intestinal flora of POI rats These findings provide important evidence for elucidating the pharmacodynamic material basis and mechanisms of SC-FL in POI, and lay a foundation for subsequent research on optimizing SC-FL efficacy through gut microbiota modulation.

R284.1;R285.61

黑龙江省自然科学基金联合基金培育项目（PL2026H199）；黑龙江省重点研发计划项目（2024ZX10B05）；龙江科技英才春雁支持计划项目（CYCX24009）