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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1207; p. 123349
• Main Authors: Fan, Lanlan, Gu, Congwen, Jiang, Yu, Cao, Gang, Sun, Li, Ho, Rodney J.Y., Wu, Deling, Han, Yanquan, Hong, Yan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-09-2022
• Subjects: Frying; GABA receptor; Molecular docking; Quality marker; Ziziphi Spinosae Semen; GABA receptor; Ziziphi Spinosae Semen; Quality marker; Molecular docking; Frying
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2022.123349

•It is the first time investigating the quality markers of traditional Chinese medicine processed products were selected by in vitro component characterization combined with receptor ligand technology.•Established the fingerprint comparison of multi batch Ziziphi Spinosae semen and fried Ziziphi Spinosae semen, combined with UPLC-Q-TOF/MS analysis method, multivariate statistical analysis and relevant literature research, to screen the differential index components of Ziziphi Spinosae semen before and after frying, and to quantitatively analyze the selected differential index components.•Then, the saturation competition experiment of rat brain tissue in vitro was carried out by Ziziphi Spinosae semen and fried Ziziphi Spinosae semen extract and diazepam, and the different chemical components reflecting the sedative and hypnotic effect before and after frying were selected.•Then, the pharmacodynamic function of the different components was verified by molecular docking technology, and the Q-markers reflecting the processing changes were selected.
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.