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Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor

Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow [Rhamnaceae; Ziziphi Spinosae Semen (ZSS)] has attracted extensive attention as the first choice of traditional Chinese medicine in the treatment of insomnia. However, recent studies on the sleep-improving mechanism of ZSS have mainly focused on th...

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Autores principales: Xiao, Fengqin, Shao, Shuai, Zhang, Hongyin, Li, Guangfu, Piao, Songlan, Zhao, Daqing, Li, Guangzhe, Yan, Mingming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722729/
https://www.ncbi.nlm.nih.gov/pubmed/36483742
http://dx.doi.org/10.3389/fphar.2022.965308
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author Xiao, Fengqin
Shao, Shuai
Zhang, Hongyin
Li, Guangfu
Piao, Songlan
Zhao, Daqing
Li, Guangzhe
Yan, Mingming
author_facet Xiao, Fengqin
Shao, Shuai
Zhang, Hongyin
Li, Guangfu
Piao, Songlan
Zhao, Daqing
Li, Guangzhe
Yan, Mingming
author_sort Xiao, Fengqin
collection PubMed
description Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow [Rhamnaceae; Ziziphi Spinosae Semen (ZSS)] has attracted extensive attention as the first choice of traditional Chinese medicine in the treatment of insomnia. However, recent studies on the sleep-improving mechanism of ZSS have mainly focused on the role of single components. Thus, to further reveal the potential mechanism of ZSS, an assessment of its multiple constituents is necessary. In this study, ZSS extract (ZSSE) was obtained from ZSS via detailed modern extraction, separation, and purification technologies. The chemical constituents of ZSSE were analyzed by high-performance liquid chromatography–mass spectrometry (HPLC–MS). For in vivo experiments, a rat model of insomnia induced by p-chlorophenylalanine (PCPA) was established to investigate the potential effect and corresponding mechanism of ZSSE on improving sleep. Hematoxylin–eosin staining (HE) results revealed that the drug group showed prominent advantages over the model group in improving sleep. Moreover, the brain levels of γ-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), and dopamine (DA) were monitored via enzyme-linked immunosorbent assay (ELISA) to further study the sleep-improving mechanism of ZSSE. We found that sleep was effectively improved via upregulation of GABA and 5-HT and downregulation of Glu and DA. In addition, molecular mechanisms of ZSSE in improving sleep were studied by immunohistochemical analysis. The results showed that sleep was improved by regulating the expression levels of GABA receptor subunit alpha-1 (GABA(A)Rα1) and GABA acid receptor subunit gamma-2 (GABA(A)Rγ2) receptors in the hypothalamus and hippocampus tissue sections. Therefore, this work not only identified the active ingredients of ZSSE but also revealed the potential pharmacological mechanism of ZSSE for improving sleep, which may greatly stimulate the prospective development and application of ZSSE.
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spelling pubmed-97227292022-12-07 Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor Xiao, Fengqin Shao, Shuai Zhang, Hongyin Li, Guangfu Piao, Songlan Zhao, Daqing Li, Guangzhe Yan, Mingming Front Pharmacol Pharmacology Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F.Chow [Rhamnaceae; Ziziphi Spinosae Semen (ZSS)] has attracted extensive attention as the first choice of traditional Chinese medicine in the treatment of insomnia. However, recent studies on the sleep-improving mechanism of ZSS have mainly focused on the role of single components. Thus, to further reveal the potential mechanism of ZSS, an assessment of its multiple constituents is necessary. In this study, ZSS extract (ZSSE) was obtained from ZSS via detailed modern extraction, separation, and purification technologies. The chemical constituents of ZSSE were analyzed by high-performance liquid chromatography–mass spectrometry (HPLC–MS). For in vivo experiments, a rat model of insomnia induced by p-chlorophenylalanine (PCPA) was established to investigate the potential effect and corresponding mechanism of ZSSE on improving sleep. Hematoxylin–eosin staining (HE) results revealed that the drug group showed prominent advantages over the model group in improving sleep. Moreover, the brain levels of γ-aminobutyric acid (GABA), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), and dopamine (DA) were monitored via enzyme-linked immunosorbent assay (ELISA) to further study the sleep-improving mechanism of ZSSE. We found that sleep was effectively improved via upregulation of GABA and 5-HT and downregulation of Glu and DA. In addition, molecular mechanisms of ZSSE in improving sleep were studied by immunohistochemical analysis. The results showed that sleep was improved by regulating the expression levels of GABA receptor subunit alpha-1 (GABA(A)Rα1) and GABA acid receptor subunit gamma-2 (GABA(A)Rγ2) receptors in the hypothalamus and hippocampus tissue sections. Therefore, this work not only identified the active ingredients of ZSSE but also revealed the potential pharmacological mechanism of ZSSE for improving sleep, which may greatly stimulate the prospective development and application of ZSSE. Frontiers Media S.A. 2022-11-22 /pmc/articles/PMC9722729/ /pubmed/36483742 http://dx.doi.org/10.3389/fphar.2022.965308 Text en Copyright © 2022 Xiao, Shao, Zhang, Li, Piao, Zhao, Li and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Xiao, Fengqin
Shao, Shuai
Zhang, Hongyin
Li, Guangfu
Piao, Songlan
Zhao, Daqing
Li, Guangzhe
Yan, Mingming
Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title_full Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title_fullStr Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title_full_unstemmed Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title_short Neuroprotective effect of Ziziphi Spinosae Semen on rats with p-chlorophenylalanine-induced insomnia via activation of GABA(A) receptor
title_sort neuroprotective effect of ziziphi spinosae semen on rats with p-chlorophenylalanine-induced insomnia via activation of gaba(a) receptor
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722729/
https://www.ncbi.nlm.nih.gov/pubmed/36483742
http://dx.doi.org/10.3389/fphar.2022.965308
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