Neurochemical Research

, Volume 41, Issue 9, pp 2233–2242 | Cite as

18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models

  • Di Wang
  • Yongfeng Zhang
  • Chunyue Wang
  • Dongxu Jia
  • Guangsheng Cai
  • Jiahui Lu
  • Di WangEmail author
  • Zhang-Jin ZhangEmail author
Original Paper


The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.


Hyperprolactinemia Serotonergic system Hormones 18β-Glycyrrhetinic acid 



18β-Glycyrrhetinic acid










Prolactin-releasing factors


Oxytocin and vasoactive intestinal peptide


Forebrain γ-aminobutyric acid


Tuberoinfundibular dopaminergic










Follicle-stimulating hormone


Luteinizing hormone


Growth hormone


Enzyme-linked immunosorbent assays


Phenylmethanesulfonyl fluoride




Glyceraldehyde-3-phosphate dehydrogenase


Horseradish peroxidase



This work was supported by the Natural Science foundation of P. R. China (Grant No. 81402955) and General Research Fund (GRF) of Research Grant Council of HKSAR (Grant No. 785813).

Compliance with Ethical Standards

Conflicts of interest

The authors declare no conflict of interest.

Supplementary material

11064_2016_1938_MOESM1_ESM.doc (11.7 mb)
Supplementary material 1 (DOC 11985 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Di Wang
    • 1
  • Yongfeng Zhang
    • 1
  • Chunyue Wang
    • 1
  • Dongxu Jia
    • 1
  • Guangsheng Cai
    • 1
  • Jiahui Lu
    • 1
  • Di Wang
    • 1
    Email author
  • Zhang-Jin Zhang
    • 2
    Email author
  1. 1.School of Life SciencesJilin UniversityChangchunChina
  2. 2.School of Chinese MedicineThe University of Hong KongHong KongChina

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