Analysis of the underlying mechanism of Ziziphi Spinosae Semen for treating anxiety disorder in a zebrafish sleep deprivation model

Abstract

Anxiety and depression are the most prevalent psychiatric disorders in the world, and they are highly comorbid with each other. Ziziphi Spinosae Semen (ZSS) is a traditional Chinese herbal medicine widely used in the treatment of insomnia and anxiety in clinical practice. To explore the effects of ZSS in alleviating anxiety in a sleep deprivation (SD) zebrafish model, the locomotor activity performance and anxiety behavior of these experimental fish were evaluated, and the underlying mechanisms of its anti-anxiety effect were examined by analyzing the transcriptomics of brain tissues. Results indicated that ZSS could significantly reduce the freezing duration and alleviate anxiety-like behavior. Moreover, ZSS was effective in promoting melatonin biosynthesis and synaptic transmission, modulating circadian rhythm, and preventing inflammatory response and oxidative stress, as evidenced by the expression alterations of the key anti-oxidation genes (GCLC, GPX1A, GSR, NRF2A and PRDX1) and pro-inflammatory cytokine (IL2RGA, IL6 and IL17A/F1). These findings will contribute to the understanding of how ZSS alleviates SD-induced anxiety, and provide a theoretical basis for the clinical application of ZSS.

Keywords

Zebrafish / Sleep deprivation / Circadian rhythm / Melatonin / Anxiety disorder

Authorship contributions

J. Zhang performed the zebrafish behavioral tests and the data analysis. C. Feng performed the anxiety model establishment and zebrafish feeding experiments. C. Feng and J. Feng wrote the manuscript with input from all authors. All of the authors were involved in proofreading and approved the final manuscript.

Ethics approval

The zebrafish experimental protocol was approved by the Zhejiang Academy of Medical Sciences Animal Experiments Ethics Committee (approval number: IACUC-20230220-15), which follows the National Institutes of Health Guidelines for the care and use of laboratory animals.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

Data will be made available on request.

Declaration of competing interest

Author C. Feng is a student of High School Affiliated to The University of Nottingham Ningbo China, and has contributed a lot to the study, but has no potential relevant financial or non-financial interests to disclose. C. Feng and J. Feng are not related. The other authors have no conflicts of interest to declare.

Acknowledgments

Not applicable.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi.org/10.1016/j.pscia.2023.100019.

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