Ginsenoside Rb1 induces a pro-neurogenic microglial phenotype via PPARγ activation in male mice exposed to chronic mild stress

J Neuroinflammation. 2021 Aug 9;18(1):171. doi: 10.1186/s12974-021-02185-0.


Background: Anti-inflammatory approaches are emerging as a new strategy for the treatment of depressive disorders. Ginsenoside Rb1 (GRb1), a major component of Panax ginseng, can inhibit inflammatory cascade and alleviate depressive-like behaviors. Microglia can promote or inhibit adult hippocampal neurogenesis according to their functional phenotypes. Here, we examine whether GRb1 may exert antidepressant effects by promoting a pro-neurogenic phenotype of microglia and thereby increasing neurogenesis.

Methods: The antidepressant effects of GRb1 or the licensed antidepressant imipramine (IMI) were assessed in chronic mild stress (CMS)-exposed male mice. The depressive-like behaviors of mice were evaluated by sucrose preference test, forced swimming test (FST), and tail suspension test (TST). The microglial phenotypes were identified by pro- and anti-inflammatory cytokine expression and morphological properties, analyzed by RT-qPCR, western blotting, and immunofluorescence staining. The effect of GRb1-treated microglia on adult hippocampal neurogenesis in vivo and in vitro was detected using immunofluorescence staining.

Results: Behavioral assessment indicated that GRb1 or IMI treatment alleviated depressive-like behaviors in CMS-exposed mice. Immunofluorescence examination demonstrated that GRb1 induced a pro-neurogenic phenotype of microglia via activating PPARγ in vivo and in vitro, which were effectively reversed by the PPARγ inhibitor GW9662. In addition, GRb1-treated microglia increased the proliferation and differentiation of neural precursor cells.

Conclusions: These findings demonstrated that GRb1 alleviated depressive-like behaviors of CMS-exposed male mice mainly through PPARγ-mediated microglial activation and improvement of adult hippocampus neurogenesis.

Keywords: Antidepressant; Ginsenoside Rb1; Major depressive disorder; Microglia; Neurogenesis; Pro-neurogenic phenotype.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Cytokines / metabolism
  • Depression / drug therapy
  • Depression / metabolism
  • Ginsenosides / pharmacology*
  • Ginsenosides / therapeutic use
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Imipramine / pharmacology
  • Imipramine / therapeutic use
  • Male
  • Mice
  • Microglia / drug effects*
  • Neurogenesis / drug effects*
  • PPAR gamma / metabolism*
  • Stress, Psychological / metabolism*


  • Cytokines
  • Ginsenosides
  • PPAR gamma
  • ginsenoside Rb1
  • Imipramine