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Licorisoflavan A Exerts Antidepressant-Like Effect in Mice: Involvement of BDNF-TrkB Pathway and AMPA Receptors

  • Dong Xiao
  • Li LiuEmail author
  • Yuanjie Li
  • Jie Ruan
  • Hanqing WangEmail author
Original Paper
  • 71 Downloads

Abstract

Depression is a highly debilitating and life-threatening psychiatric disorder. The classical antidepressants are still not adequate due to undesirable side effects. Therefore, the development of new drugs for depression treatment is an urgent strategic to achieving clinical needs. Licorisoflavan A is a bioactive ingredient isolated from Glycyrrhizae Radix and has been recently reported for neuroprotective effects. In this study, the antidepressant-like effect and neural mechanism of licorisoflavan A were explored. In the mice behavioral despair test, we observed that licorisoflavan A exhibited powerful antidepressant-like effect in forced swimming test (FST), tail suspension test (TST), without affecting locomotor activity in open field test (OFT). Additionally, licorisoflavan A administration significantly restored Chronic mild stress (CMS)-induced changes in sucrose preference test (SPT), FST, and TST, without altering the locomotion in OFT. In chronical-stimulated mice, the licorisoflavan A treatment effectively attenuated the expressions of Brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), the phosphorylations of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK)-1/2, eukaryotic elongation factor 2 (eEF2), mammalian target of rapamycin (mTOR), initiation factor 4E-binding protein 1 (4E-BP-1), and p70 ribosomal protein S6 kinase (p70S6K) in hippocampus of CMS-induced mice. Additionally, licorisoflavan A could reverse the decreases in synaptic proteins post-synaptic density protein 95 (PSD-95) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) caused by CMS, and its antidepressant-like effect was blocked by the AMPA receptor antagonist NBQX. These findings served as preclinical evidence that licorisoflavan A exerted potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors. Licorisoflavan A might be used as a potential medicine against depression-like disorder.

Keywords

Licorisoflavan A Antidepressant-like effect Chronic mild stress BDNF-TrkB signaling pathway AMPA 

Abbreviations

FST

Forced swimming test

TST

Tail suspension test

SPT

Sucrose preference test

OFT

Open field test

CMS

Chronic mild stress

BDNF

Brain-derived neurotrophic factor

TrkB

Tyrosine kinase B

CREB

cAMP response element binding protein

ERK

Extracellular signal-regulated kinase

eEF2

Eukaryotic elongation factor 2

mTOR

Mammalian target of rapamycin

4E-BP-1

4E-binding protein 1

p70S6K

p70 ribosomal protein S6 kinase

PSD-95

Post-synaptic density protein 95

AMPA

α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid

GluR1

Glutamate receptor 1

NBQX

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81873096, 81603227, 81503465, 81460645), Chanzhou Sci & Tech Program (2017333), Ningxia key research and development plan (2016KJHM46), Eastern United Western Science and Technology Cooperation Project (2017BY079).

Compliance with Ethical Standards

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of PharmacyGuangdong Medical UniversityDongguanChina
  2. 2.College of PharmacyNingxia Medical UniversityNingxiaChina
  3. 3.College of Traditional Chinese MedicineChina Pharmaceutical UniversityNanjingChina
  4. 4.Ningxia Research Center of Modern Hui Medicine Engineering and TechnologyNingxia Medical UniversityYinchuanChina

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