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

BackgroundThe 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.MethodsIts 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.ResultsMatrine 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.ConclusionMatrine may ameliorate CUMS-induced depression in mice by modulating the microbiota-gut-brain axis.

Automated summary

By modulating the microbiota-gut-brain axis, matrine can alleviate depression, reduce inflammation, and increase the levels of brain-derived neurotrophic factor (BDNF).