Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes

J Ethnopharmacol. 2017 Aug 17:208:207-213. doi: 10.1016/j.jep.2017.06.031. Epub 2017 Jun 20.

Abstract

Ethnopharmacological relevance: Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC.

Materials and methods: Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24h to induce gap junction damage. Rg1 (0.1, 1, or 10μM) or fluoxetine (1μM) was added 1h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions.

Results: Treatment of primary astrocytes with CORT for 24h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1μM and 10μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation.

Conclusion: These findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression.

Keywords: Astrocyte; Cx43; Depression; Gap junction; Ginsenoside Rg1.

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Communication / drug effects
  • Cells, Cultured
  • Connexin 43 / metabolism
  • Corticosterone
  • Down-Regulation
  • Gap Junctions / drug effects*
  • Gap Junctions / physiology
  • Ginsenosides / pharmacology*
  • Hippocampus / cytology
  • Phosphorylation / drug effects
  • Prefrontal Cortex / cytology
  • Rats

Substances

  • Connexin 43
  • Ginsenosides
  • Gja1 protein, rat
  • ginsenoside Rg1
  • Corticosterone