, Volume 236, Issue 9, pp 2823–2834 | Cite as

Paeoniflorin attenuates impairment of spatial learning and hippocampal long-term potentiation in mice subjected to chronic unpredictable mild stress

  • Si-Cheng Liu
  • Wei-Yan Hu
  • Wei-Yuan Zhang
  • Lu Yang
  • Yan Li
  • Zhi-Cheng Xiao
  • Ming ZhangEmail author
  • Zhi-Yong HeEmail author
Original Investigation


Rationale and objective

Paeoniflorin has been reported to exhibit antidepressant-like effects in several animal model depression; and it also exerts a neuroprotective effect. In the present study, we investigated the effects of paeoniflorin administration on depression-like behaviors and cognitive abilities in mice subjected to chronic unpredictable mild stress (CUMS), an animal model associated with depressive disorders and cognitive deficits.


We administered paeoniflorin (20 mg/kg), which is the main active constituent extracted from Paeonia lactiflora Pall. and exerts multiple pharmacological actions, to CUMS mice. Subsequently, animals were subjected to tests of depression-like behavior including the sucrose preference test, the forced swimming test and the tail suspension test. The Morris water maze (MWM) task was applied to evaluate learning and memory capacity. Hippocampal CA1 long-term potentiation (LTP) was recorded. Dendritic spine density and the expression levels of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) in the hippocampus were also investigated.


The administration of paeoniflorin protected against CUMS-induced depression-like behavior. Paeoniflorin also improved the performance of CUMS mice in the MWM. The impairment of hippocampal CA1 LTP caused by CUMS was also reversed. Furthermore, paeoniflorin administration prevented decreases in dendritic spine density and in the expression of BDNF and PSD95 in the hippocampus of CUMS mice.


Our observations suggest that paeoniflorin is a potential antidepressant that protects against cognitive impairment in depression.


Paeoniflorin CUMS LTP Spine density Morris water maze 





Chronic unpredictable mild stress (CUMS)


Morris water maze


Sucrose preference test


Forced swimming test


Tail suspension test


Long-term potentiation


Brain-derived neurotrophic factor


Postsynaptic density protein 95


Artificial cerebrospinal fluid




Funding information

This work was supported by the National Natural Science Program of China (81860254, Z.Y.H.; 81360175, M. Z), the Joint Program of Yunnan Province and Kunming Medical University (2017FE468-249, Z.Y.H. 2015FB006, W. Y. H), and the support provided by Yunnan Key Laboratory of Stem Cell and Regenerative Medicine (Z. Y. H., M. Z. and W.Y.H.) is also appreciated.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Si-Cheng Liu
    • 1
    • 2
  • Wei-Yan Hu
    • 1
    • 3
    • 4
  • Wei-Yuan Zhang
    • 1
  • Lu Yang
    • 1
  • Yan Li
    • 1
  • Zhi-Cheng Xiao
    • 1
    • 3
  • Ming Zhang
    • 1
    Email author
  • Zhi-Yong He
    • 1
    • 3
    Email author
  1. 1.Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical MedicineKunming Medical UniversityKunmingChina
  2. 2.Department of Medical OncologyThe Third Affiliated Hospital of Kunming Medical UniversityKunmingChina
  3. 3.Department of Anatomy and Developmental BiologyMonash UniversityMelbourneAustralia
  4. 4.School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural ProductsKunming Medical UniversityKunmingChina

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