The effects of berberine on depressive symptoms: a systematic review and meta-analysis of preclinical studies

Li et al., 2025 | Front Psychiatry | Systematic Review

Citation

Li Xiaona, Lu Mei, ... Zhou Jiamei. The effects of berberine on depressive symptoms: a systematic review and meta-analysis of preclinical studies. Front Psychiatry. 2025;16:1653929. doi:10.3389/fpsyt.2025.1653929

Abstract

INTRODUCTION: Despite preclinical evidence for berberine's antidepressant potential, its pharmacological effects remain controversial.This study therefore systematically reviews animal research to clarify its mechanisms and support future clinical trials. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, and OVID for studies on berberine in depression models up to March 20, 2025. Analysis used STATA 15.0 and Review Manager 5.4, with study quality assessed via SYRCLE's risk of bias tool. RESULTS: The meta-analysis included 18 studies (338animals). Overall, berberine significantly reduced depression-like behaviors in animal models.Specifically, BBR increased total locomotor activity in the open field test (SMD=2.79, 95% CI: 1.55, 4.02) and time spent in the center zone (SMD=2.49, 95% CI:1.61, 3.37), reduced immobility time in both the forced swim test and tail suspension test (SMD =-4.42, 95% CI:-5.77,-3.07; SMD=-4.46, 95% CI:-6.21, -2.71), increased sucrose intake in the sucrose preference test (SMD = 3.72, 95% CI: 2.37, 5.07), and reduced feeding latency in the novelty-suppressed feeding test (SMD=-5.72, 95% CI:-7.63, -3.82). However, BBR did not significantly alter the number of square crossings (SMD=1.36, 95%CI:-0.07 , 2.79) or rearing frequency (SMD=1.66, 95% CI: -0.29, 3.61) in the open field test. BBR also increased the levels of body weight, brain-derived neurotrophic factor, dopamine, serotonin, and norepinephrine,while reducing the levels of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. DISCUSSION: Preclinical studies suggest that berberine may represent a promising therapeutic agent for the treatment of depressive disorders. Its antidepressant effects appear to be closely associated with the modulation of neurotransmitter levels,reduction of oxidative stress, and inhibition of inflammatory responses.However, methodological limitations may constrain these findings. Larger, more rigorous preclinical studies are needed for confirmation. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2025-6-0002, identifier INPLASY202560002.

Key Findings

The meta-analysis included 18 studies (338animals). Overall, berberine significantly reduced depression-like behaviors in animal models.Specifically, BBR increased total locomotor activity in the open field test (SMD=2.79, 95% CI: 1.55, 4.02) and time spent in the center zone (SMD=2.49, 95% CI:1.61, 3.37), reduced immobility time in both the forced swim test and tail suspension test (SMD =-4.42, 95% CI:-5.77,-3.07; SMD=-4.46, 95% CI:-6.21, -2.71), increased sucrose intake in the sucrose preferen

Outcomes Measured

  • depression
  • inflammatory markers

Population

Field Value
Population See abstract
Sample Size 18
Age Range See abstract
Condition depression

MeSH Terms

  • No MeSH terms indexed

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: berberine

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09