Paeoniflorin ameliorates depressive behaviours by modulating microbiota-gut-brain axis functions.

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Major depressive disorder (MDD) is a global health concern linked to gut-brain axis dysfunction.
• Paeoniflorin, a natural compound, shows antidepressant potential, but its mechanisms are unclear.

Purpose of the Study:

• To investigate paeoniflorin's effects on depression-like behaviors in rats.
• To explore paeoniflorin's modulation of the gut-brain axis, including microbiota and metabolites.
• To understand the neurobiological mechanisms underlying paeoniflorin's antidepressant action.

Main Methods:

• Chronic unpredictable mild stress (CUMS) induced depression-like behaviors in rats.
• Assessed antidepressant effects via behavioral tests, 16S rRNA sequencing, and metabolomic analysis.
• Investigated neuroinflammation, synaptic plasticity, and gut barrier integrity.

Main Results:

• Paeoniflorin significantly reduced depression-like behaviors and cognitive deficits in CUMS rats.
• Paeoniflorin modulated gut microbiota composition and diversity, enriching amino acid metabolism pathways.
• Microbial metabolites correlated with improved neuroinflammation and synaptic plasticity.

Conclusions:

• Gut microbiota and metabolite disruptions contribute to depression via impaired gut-brain interactions.
• Paeoniflorin exerts neuroprotective and antidepressant effects by modulating gut-brain axis function.
• Targeting the gut-brain axis with paeoniflorin offers a promising therapeutic strategy for MDD.