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Metabolic Brain Disease

, Volume 33, Issue 5, pp 1413–1420 | Cite as

Gentiopicroside abrogates lipopolysaccharide-induced depressive-like behavior in mice through tryptophan-degrading pathway

  • Ya-ting Deng
  • Ming-gao Zhao
  • Tian-jiao Xu
  • Jin-Hou
  • Xin-hua Li
Original Article

Abstract

Targeting neuroinflammatory disturbances has been acknowledged as a potential strategy for treatment of depressive disorder in humans. Over-activation of tryptophan-degrading pathway by pro-inflammatory cytokines resulted in N-methyl-d-aspartate (NMDA)-mediated excitotoxicity, which is implicated in pathophysiology of depression. Gentiopicroside (Gent) has powerful anti-inflammatory property and exhibits promising antidepressant effect in an animal model of pain/depression dyad by down-regulating GluN2B-containing NMDA receptors. Therefore, the present study aimed to investigate the ability of Gent to abolish depressive-like behavior induced by lipopolysaccharide (LPS) in mice. Acute administration of LPS (0.5 mg/kg, i.p.) increased immobility time in both forced swimming test (FST) and tail suspension test (TST) without affecting spontaneous locomotor activity, indicative of depressive-like behavior. Gent (50 mg/kg, i.p.) administered once a day for three consecutive days prevented the development of depressive-like behavior induced by LPS. The antidepressant-like effect was paralleled with restoration of LPS-induced alterations in brain inflammatory mediators (i.e. IL-1β and TNF-α). In addition, Gent prevented over-activation of indoleamine 2,3-double oxygen enzyme (IDO) and recovered GluN2B subunit expression in the PFC challenged by LPS. In conclusion, our results suggested that Gent pretreatment provided protection against LPS-induced depressive-like behavior and the effect appeared to be demonstrated, at least partially, by blocking various steps of tryptophan-degrading pathway.

Keywords

Gentiopicroside Depressive-like behavior LPS Tryptophan-degrading pathway 

Abbreviations

Gent

Gentiopicroside

LPS

Lipopolysaccharide

MDD

Major depressive disorder

IDO

Indoleamine 2,3-double oxygen enzyme

FST

Forced swimming test

TST

Tail suspension test

OP

Open field

NMDA

N-methyl-d-aspartate

CNS

Central nervous system

BLA

Basolateral amygdala

PFC

Prefrontal cortex

Notes

Acknowledgements

This research was supported by National Natural Science Foundation of China, No. 81403064; Doctoral research foundation of Xi’an Medical University, No. 2016DOC23 and Nature science research plan in shannxi province of China, No.2016JM8047.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, School of PharmacyXi’an Medical UniversityXi’anChina
  2. 2.Department of PharmacologyFourth Military Medical UniversityXi’anChina

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