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炮制前后酸枣仁镇静催眠作用的不同化学组分筛选及 Q 标志物研究。

Screening of different chemical components of sedative and hypnotic effects of Ziziphi Spinosae Semen before and after frying and determination of the Q-Marker.

机构信息

Grade Three-level Laboratory of TCM Preparation, State Administration of Traditional Chinese Medicine, The First Affiliated Hospital/College of integrated Chinese and Western Medicine of Anhui University of Chinese Medicine, Hefei 230031, China; Anhui University of Chinese Medicine, Hefei 230031, China.

Zhejiang Chinese Medical University, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Sep 1;1207:123349. doi: 10.1016/j.jchromb.2022.123349. Epub 2022 Jul 1.

DOI:10.1016/j.jchromb.2022.123349
PMID:35849979
Abstract

Ziziphi Spinosae Semen (ZSS) is a traditional Chinese medicine used for sedation and hypnosis. Preliminary studies have shown that frying it could increase its sedative and hypnotic effects due to an increase in its chemical contents. However, the correlation between increased ZSS contents and therapeutic effects remains unclear. This study aimed to identify chemical components that change between ZSS and Fried Ziziphi Spinosae Semen (FZSS) and Q-markers related to these changed components' sedative and hypnotic effects. Differences between ZSS and FZSS were investigated using the UPLC fingerprint analysis. Components significantly different between ZSS and FZSS were screened using the UPLC-Q-TOF-MS analysis combined with a multivariate statistical method. In addition, ZSS and FZSS extracts were treated with diazepam in vitro to observe their differences in saturation competition between ZSS extract and diazepam, before and after processing, and diazepam on the GABA receptor in SD rats' brain tissue. Then, the chemical components of ZSS and FZSS that competed with diazepam to bind to the GABA receptor were identified by LC-MS/MS analysis. Finally, the binding efficiency of the different medicinal components was assessed using molecular docking technology. The results indicated significant differences in the content of various chemical components between ZSS and FZSS. Among them, the contents of adenosine, spinosin, 6'″-feruloylspinosin, jujuboside A and betulinic acid were found to be significantly increased after frying. LC-MS/MS and molecular docking analysis screened spinosin, 6'″-feruloylspinosin and betulinic acid as Q markers for the sedative and hypnotic effects of ZSS and FZSS. In summary, this study identified the changed sedative-hypnotic chemical components and Q-markers of ZSS before and after frying.

摘要

酸枣仁是一种传统的中药,具有镇静和催眠作用。初步研究表明,炒制可以增加其镇静和催眠作用,这可能是由于其化学成分的增加。然而,增加的酸枣仁含量与治疗效果之间的相关性尚不清楚。本研究旨在鉴定酸枣仁与炒酸枣仁之间变化的化学成分和与这些变化成分的镇静和催眠作用相关的 Q 标志物。采用 UPLC 指纹图谱分析研究了酸枣仁和炒酸枣仁之间的差异。采用 UPLC-Q-TOF-MS 分析结合多变量统计方法筛选出酸枣仁和炒酸枣仁之间差异显著的成分。此外,用安定对酸枣仁和炒酸枣仁提取物进行体外处理,观察处理前后酸枣仁提取物与安定之间的饱和竞争差异,以及安定对 SD 大鼠脑组织中 GABA 受体的影响。然后,通过 LC-MS/MS 分析鉴定与安定竞争结合 GABA 受体的酸枣仁和炒酸枣仁的化学成分。最后,采用分子对接技术评估不同药用成分的结合效率。结果表明,酸枣仁和炒酸枣仁之间的各种化学成分含量存在显著差异。其中,腺苷、酸枣仁皂苷、6'″-阿魏酰酸枣仁皂苷、酸枣仁皂苷 A 和白桦脂酸的含量在炒制后明显增加。LC-MS/MS 和分子对接分析筛选出酸枣仁皂苷、6'″-阿魏酰酸枣仁皂苷和白桦脂酸作为酸枣仁和炒酸枣仁镇静催眠作用的 Q 标志物。综上所述,本研究鉴定了酸枣仁炒制前后变化的镇静催眠化学成分和 Q 标志物。

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