目的 从肠道菌群代谢转化的角度，研究酸枣仁水提取物转化前后原型及代谢产物。方法 酸枣仁水提取物与正常人肠道菌群在厌氧条件下分别共孵育0.083、1、4、12、24 h。采用超高效液相色谱-高分辨质谱分析技术，对孵育液中的化合物进行鉴定并分析代谢途径，继而以化合物峰面积百分比为指标，绘制不同时间点孵育液中黄酮、皂苷和生物碱类成分的变化规律。结果 酸枣仁水提取物中共表征了31种原型成分，转化后的提取物中鉴定了4个代谢产物。苄基异喹啉类生物碱转化24 h内无明显降解。黄酮类成分的代谢反应类型丰富且反应程度剧烈，在24 h内降解完全。酸枣仁皂苷A和B主要发生水解反应。乌药碱、酸李碱、山柰酚-3-O-芸香糖苷、斯皮诺素、维采宁、酸枣仁皂苷A和B可作为酸枣仁潜在质量标志物（Q-marker）。结论 将肠道菌群体外转化作为逆向佐证体内研究结果的一种方式，为中药Q-marker的预测提供一种新思路和新途径。

Objective The aim of this work was to investigate the quality markers (Q-markers) of Ziziphi Spinosae Semen (ZSS) based on biotransformation by human intestinal microbiota. Methods In this study, in vitro biotransformation of ZSS aqueous extract by normal human intestinal microbiota was analyzed using UPLC-Q-Orbitrap-MS. Furthermore, the time course of the biotransformation was studied to probe into the biotransformation mechanism of compounds in ZSS by human intestinal flora. The change rules of flavonoids, saponins and alkaloids in the incubation solution at different time points were plotted based on the percentage of peak area of compounds. Results A total of 31 original ingredients and four metabolites were characterized in transformed ZSS aqueous extract by human intestinal microbiota. No obvious degradation was observed for benzylisoquinoline alkaloids within 24 h. As far as flavones concerned, a wide range of metabolic reactions as well as significant reaction were shown. Meanwhile, these flavonoids were completely degraded during 24 h. In addition, both jujuboside A and jujuboside B were metabolized to their saponins by deglycosylation reactions. Thus, coclaurine, zizyphusine, kaempferol-3-O-rutinoside, spinosin, vicenin Ⅱ, jujuboside A, and jujuboside B were referred as prospective Q-markers. Conclusion The results indicated that the chemical compounds in ZSS were obviously affected by transformation. Intestinal transformation studies play an important role for the elucidation of therapeutic material basis of ZSS and it should be taken into account during the process of the investigation of Q-marker.

国家自然科学基金青年基金资助项目（81603289）；国家自然科学基金青年基金资助项目（81603251）；山西省重点研发计划项目（201803D31087）；山西省科技攻关计划——振东专项（2016ZD0105）；山西省科技攻关计划——振东专项（2016ZD0104）；晋药综合开发利用协同创新中心项目（2017-JYXT-25）；山西中医药大学科技创新团队（2018-TD-009）