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Purpurin exerted antidepressant-like effects on behavior and stress axis reactivity: evidence of serotonergic engagement

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Abstract

Rationale and objectives

Major depression represents a significant public health problem worldwide, and effective regimen is lacking. The present study investigated the antidepressant-like effects of purpurin, a natural anthraquinone compound from Rubia tinctorum L., and explored the underlying mechanism(s).

Methods

Forced swim test (FST) and tail suspension test (TST) were used to assess antidepressant-like effects of purpurin in mice. Effects of purpurin on neuroendocrine responsivity were evaluated at the level of corticosterone and ACTH following acute restraint stress and intracerebroventricular injection of corticotrophin-releasing-factor (CRF). Serotonergic mechanisms underlying purpurin antidepressant effect were explored using biochemical, neurochemical, and pharmacological paradigms.

Results

Chronic purpurin treatment exerted in mice dose-dependently antidepressant-like effects on behavior and stress axis reactivity (n = 9–11 per group). The purpurin-triggered antidepressant-like effects are serotonergically dependent, since purpurin-treated mice showed escalated levels of brain serotonin and suppressed monoamine oxidase (MAO) activity (n = 8–11 per group). Consistently, chemical depletion of brain serotonin by p-chlorophenylalanine (PCPA) abolished the antidepressant-like effects of purpurin on behavior and stress axis responsivity (n = 9–10 per group). Moreover, the antidepressant effect by purpurin was preferentially counteracted by 1A-selective 5-HT receptor antagonist WAY-100635, but potentiated by 1A-selective agonist 8-OH-DPAT and sub-effective dose of serotonergic antidepressant fluoxetine (n = 9–11 per group), suggesting a crucial role for 5-HT1A related serotonergic system in mediating such purpurin antidepressant effect.

Conclusion

We have revealed the antidepressant-like effects of purpurin on both behavior and stress axis reactivity in mice, with serotonergic system that preferentially couples with 5-HT1A receptors being critically engaged.

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Funding

This project was sponsored by National Basic Research Program of China (2015CB553504), National Natural Science Foundation of China (81541087 and U1132602), Natural Science Foundation of Zhejiang Province (LY18H310006), and Innovative Research Team of Ningbo (2015C110026).

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Authors and Affiliations

  1. Department of Neurology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China

    Li Ma

  2. Department of Vasculocardiology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei Province, China

    Pei Hu

  3. Department of Pharmacology, Ningbo University, School of Medical Science, Ningbo, China

    Junfang Zhang, Wugeng Cui & Xin Zhao

Authors
  1. Li Ma
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  2. Pei Hu
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  3. Junfang Zhang
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  4. Wugeng Cui
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  5. Xin Zhao
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Corresponding authors

Correspondence to Wugeng Cui or Xin Zhao.

Ethics declarations

Institutional Animal Ethics Committee approved the experimental protocol. The experiments were performed following the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines.

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The authors declare that they have no conflict of interest.

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Ma, L., Hu, P., Zhang, J. et al. Purpurin exerted antidepressant-like effects on behavior and stress axis reactivity: evidence of serotonergic engagement. Psychopharmacology 237, 887–899 (2020). https://doi.org/10.1007/s00213-019-05422-w

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  • DOI: https://doi.org/10.1007/s00213-019-05422-w

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