Yan Yan, Liu Jiaxing, Zhang Min, Zhang Yinjie, Shi Biyun, Qin Xuemei, Du Chenhui
Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.
Thermo Fisher Scientific (China), Co., Ltd, Beijing, China.
Biomed Chromatogr. 2023 Jan;37(1):e5530. doi: 10.1002/bmc.5530. Epub 2022 Nov 20.
Ziziphi Spinosae semen (ZSS), the dried and ripe seed of Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou, has been used as a sedative in China and other Asian countries for over a millennium. However, its quality markers (Q-markers) are not completely clear. In this study, Q-markers selected by a metabolic in vivo study combined with network pharmacology are proposed for ZSS quality control. An UHPLC (ultra-high-performance liquid chromatography)-Q-Orbitrap-MS method was developed to identify or tentatively assign 48 components including 21 flavonoid C-glycosides, 2 flavonoid O-glycosides, 11 dammarane triterpenoid saponins, 13 alkaloids, and 1 other, using a diagnostic product ion filtering strategy in ZSS. Subsequently, 147 metabolites detected from serum, urine, bile, and feces samples of para-chlorophenylalanine-induced insomnia rats treated with ZSS aqueous extracts could be linked to their respective parent compounds, including 27 prototypes. Meanwhile, three metabolic networks of flavonoids, saponins, and alkaloids are preliminarily established and potential metabolic pathways are investigated under the insomnia condition. Finally, 12 key bioactive components against insomnia including magnoflorine, caaverine, coclaurine, norisocorydine, genkwanin, juzinrine, apigenin, jujubogenin, kaempferol-3-O-rutinoside, jujuboside A, jujuboside B, and spinosin with the highest degree values in component-target-pathways network were selected as Q-markers for the quality control of ZSS.
酸枣仁为鼠李科植物酸枣Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou干燥成熟的种子，在中国及其他亚洲国家作为镇静剂使用已逾千年。然而，其质量标志物（Q-标志物）尚不完全明确。本研究通过体内代谢研究结合网络药理学的方法筛选出酸枣仁的Q-标志物，用于其质量控制。建立了超高效液相色谱-四极杆-轨道阱高分辨质谱（UHPLC-Q-Orbitrap-MS）方法，采用诊断性产物离子过滤策略，对酸枣仁中的48种成分进行了鉴定或初步定性，包括21种黄酮碳苷、2种黄酮氧苷、11种达玛烷型三萜皂苷、13种生物碱及1种其他成分。随后，从给予酸枣仁水提取物的对氯苯丙氨酸诱导的失眠大鼠的血清、尿液、胆汁和粪便样本中检测到的147种代谢产物可与其各自的母体化合物相关联，其中包括27种原型化合物。同时，初步建立了黄酮类、皂苷类和生物碱类三个代谢网络，并对失眠状态下的潜在代谢途径进行了研究。最后，选取在成分-靶点-通路网络中度数值最高的12种抗失眠关键生物活性成分，即木兰碱、去氢骆驼蓬碱、衡州乌药碱、去甲异紫堇定、芫花素、酸枣仁碱、芹菜素、酸枣仁皂苷元、山柰酚-3-O-芸香糖苷、酸枣仁皂苷A、酸枣仁皂苷B和斯皮诺素，作为酸枣仁质量控制的Q-标志物。
