Matrine alleviates depressive-like behaviors via modulating microbiota-gut-brain axis in CUMS-induced mice

J Transl Med. 2023 Feb 24;21(1):145. doi: 10.1186/s12967-023-03993-z.

Abstract

Background: The realization of the "microbiota-gut-brain" axis plays a critical role in neuropsychiatric disorders, particularly depression, is advancing rapidly. Matrine is a natural bioactive compound, which has been found to possess potential antidepressant effect. However, the underlying mechanisms of regulation of the "microbiota-gut-brain" axis in the treatment of depression by oral matrine remain elusive.

Methods: Its antidepressant effects were initially evaluated by behavioral tests and relative levels of monoamine neurotransmitters, and matrine has been observed to attenuate the depression-like behavior and increase neurotransmitter content in CUMS-induced mice. Subsequently, studies from the "gut" to "brain" were conducted, including detection of the composition of gut microbiota by 16S rRNA sequencing; the metabolomics detection of gut metabolites and the analysis of differential metabolic pathways; the assessment of relative levels of diamine oxidase, lipopolysaccharide, pro-inflammatory cytokines, and brain-derived neurotrophic factor (BDNF) by ELISA kits or immunofluorescence.

Results: Matrine could regulate the disturbance of gut microbiota and metabolites, restore intestinal permeability, and reduce intestinal inflammation, thereby reducing the levels of pro-inflammatory cytokines in peripheral blood circulation and brain regions, and ultimately increase the levels of BDNF in brain.

Conclusion: Matrine may ameliorate CUMS-induced depression in mice by modulating the "microbiota-gut-brain" axis.

Keywords: Depression; Gut microbiota; Matrine; Metabolomics; Microbiota–gut–brain axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Brain-Gut Axis
  • Cytokines / metabolism
  • Depression* / metabolism
  • Matrines
  • Mice
  • RNA, Ribosomal, 16S
  • Stress, Psychological / metabolism
  • Stress, Psychological / psychology

Substances

  • Brain-Derived Neurotrophic Factor
  • Matrines
  • RNA, Ribosomal, 16S
  • Antidepressive Agents
  • Cytokines