The Effect of Semen Ziziphi Spinosae Extract on the p38MAPK/NF-κB Signaling Pathway in Insomniac Rats

Abstract

Objective The objective of the study was to explore whether Suanzaoren (Semen Ziziphi Spinosae, SZS) extract could improve insomnia by inhibiting the p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-κB (NF-κB) signaling pathway.

Methods Forty SPF-grade Sprague-Dawley (SD) rats were included in the study, with 10 randomly selected rats serving as the control group. The remaining rats were injected intraperitoneally with p-chlorophenylalanine (PCPA) for 6 days to establish an insomnia model. After successful modeling, the rats were divided into the model group, SZS extract group (3.0 g/kg), and zopiclone group (1.25 g/kg). The rats in the SZS extract and zopiclone groups were administered with the corresponding drugs via gavage for 7 days, while the rats in the control and model groups received distilled water. Sleep latency and sleep duration were recorded, and behavioral changes were observed through elevated plus-maze and open field tests. The levels of oxidative stress markers and serum inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of p38 MAPK, p-p38MAPK, p-NF-κBp65, and NF-κBp65 protein in the cerebral cortex were detected by Western blot. Neuronal structures in the cerebral cortex were observed under a transmission electron microscope.

Results Compared with the control group, the model group exhibited abnormal appearances, significant body mass loss (p < 0.001), prolonged sleep latency and shortened sleep duration (p < 0.001). The SZS extract and zopiclone groups showed significant improvements in these parameters compared with the model group. Compared with the control group, the model group showed significant reduction in total movement distance (p < 0.001), fewer entries into the central zone (p < 0.01), and significant decrease in rearing frequency (p < 0.001); the levels of glutathione peroxidase (GSH-Px) and catalase (CAT) in the hippocampus were significantly reduced (p < 0.001); the serum levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the expression levels of p-p38MAPK and p-NF-κBp65 in the cerebral cortex were significantly increased (p < 0.05). Compared with the model group, the SZS extract group showed significant increase in movement distance (p < 0.01) and rearing frequency (p < 0.001), significantly increased the GSH-Px and CAT levels (p < 0.001), and decreased the IL-1β and TNF-α levels (p < 0.01); furthermore, the SZS extract group showed a significantly reduced p-p38MAPK and p-NF-κBp65 levels (p < 0.05). The SZS extract group showed significant improvement in the neuronal structure compared with the model group.

Conclusion SZS extract can inhibit the p38MAPK/NF-KB signaling pathway to improve insomnia.

Keywords

Semen Ziziphi Spinosae extract - p38MAPK/NF-κB signaling pathway - insomnia - oxidative stress - inflammatory factors

CRediT Authorship Contribution Statement

Mingyu Ji: Conceptualization, investigation, data curation, formal analysis, methodology, validation, visualization, writing -original draft. Wei Xiong, Zijing Xu, Peipei Zhang: Investigation, data curation, methodology. Shuyu Li, Qian Wang, Dexian Jia: Funding acquisition, project administration, resources, supervision, writing-review & editing.

Publication History

Received: 21 September 2024

Accepted: 29 October 2024

Article published online:
30 December 2024

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