Polygonum sibiricum polysaccharides exert the antidepressant-like effects in chronic unpredictable mild stress-induced depressive mice by modulating microbiota-gut-brain axis

Phytother Res. 2023 Aug;37(8):3408-3423. doi: 10.1002/ptr.7813. Epub 2023 Mar 30.

Abstract

Polygonum sibiricum polysaccharides (PSP) are one of the main active components of Polygonatum sibiricum, which is a traditional Chinese medicine with food and drug homologies. Recent studies have revealed the antidepressant-like effects of PSP. However, the precise mechanisms have not been clarified. Therefore, the present study was conducted to explore that whether PSP could exert the antidepressant-like effects via microbiota-gut-brain (MGB) axis in chronic unpredictable mild stress (CUMS)-induced depressive mice by transplantation of fecal microbiota (FMT) from PSP administration mice. FMT markedly reversed the depressive-like behaviors of CUMS-induced mice in the open field, the sucrose preference, the tail suspension, the forced swimming, and the novelty-suppressed feeding tests. FMT significantly increased the levels of 5-hydroxytryptamine and norepinephrine, decreased the levels of the pro-inflammatory cytokines in the hippocampus and reduced the levels of corticosterone, an adrenocorticotropic-hormone, in the serum of CUMS-induced mice. In addition, administration of PSP and FMT significantly increased the expressions of ZO-1 and occludin in the colon and decreased the levels of lipopolysaccharide and interferon-γ in the serum of CUMS-induced mice. Moreover, administration of PSP and FMT regulated the signaling pathways of PI3K/AKT/TLR4/NF-κB and ERK/CREB/BDNF. Taken together, these findings indicated that PSP exerted antidepressant-like effects via the MGB axis.

Keywords: Polygonum sibiricum polysaccharides; depression; fecal microbiota transplantation; gut barrier; microbiota-gut-brain axis.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Brain-Gut Axis
  • Depression* / drug therapy
  • Depression* / metabolism
  • Disease Models, Animal
  • Hippocampus
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polygonum* / metabolism
  • Polysaccharides / metabolism
  • Polysaccharides / pharmacology
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism

Substances

  • Phosphatidylinositol 3-Kinases
  • Antidepressive Agents
  • Polysaccharides