Brain research bulletinDec 21, 2025

Puerarin may reduce brain inflammation and anxiety-like behavior in mice by changing gut bacteria through the brain-gut connection

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 19, 2026

Abstract

Puerarin significantly improved open arm entries and open arm time in mice exhibiting anxiety-like behavior induced by lipopolysaccharide.

Increased inflammatory cytokine levels and reduced intestinal tight junction protein expression were observed in mice after LPS treatment.
LPS treatment led to decreased microbial diversity and an increase in pro-inflammatory bacterial genera.
High-dose puerarin administration improved open arm entries and open arm time in the elevated plus maze.
Puerarin treatment also reduced inflammatory cytokine levels, restored tight junction protein expression, and enhanced microbial diversity.
Positive correlations were found between beneficial bacteria (Lactobacillus and Akkermansia) and anxiety-like behavior measures, while Escherichia-Shigella showed a negative correlation.

Simplified

BACKGROUND: The gut-brain axis (GBA) has been increasingly recognized as a potential contributor to anxiety pathophysiology. Puerarin possesses anti-inflammatory, antioxidant, and neuroprotective properties, but its anxiolytic mechanism via the GBA remains unclear. The intervention of puerarin on lipopolysaccharide (LPS)-induced anxiety-like behavior (ALB) in mice was investigated based on the GBA theory.

METHODS: Forty mice were allocated at random: control, LPS, LPS+PueL (low-dose puerarin), and LPS+PueH (high-dose puerarin) groups (n = 10 each). ALB was evaluated by the elevated plus maze (EPM). Inflammatory cytokines were measured by ELISA. Tight junction proteins were detected by qPCR and Western blot. Gut microbiota (GM) was analyzed by 16S rRNA sequencing.

RESULTS: Compared with the Control, open arm entries (OAE) and open arm time (OAT) were decreased, inflammatory cytokine levels were elevated, intestinal tight junction protein expression was down-regulated, microbial diversity was reduced, and the abundance of pro-inflammatory bacterial genera was obviously increased in the LPS. In the LPS+PueH, OAE and OAT, inflammatory cytokine levels, tight junction protein expression, microbial diversity, and abundance of beneficial bacterial genera were evidently improved (P < 0.05). Correlation analysis revealed that Lactobacillus and Akkermansia were positively correlated with OAE and OAT, whereas Escherichia-Shigella was negatively correlated (P < 0.05).

CONCLUSION: Puerarin alleviated LPS-induced ALB in mice by suppressing neuroinflammation, restoring intestinal barrier integrity, and modulating GM balance, which was closely associated with GBA regulation.

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Puerarin may reduce brain inflammation and anxiety-like behavior in mice by changing gut bacteria through the brain-gut connection

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