Abstract
BACKGROUND: Depression is a prevalent global disorder that imposes a significant burden on individuals worldwide. Berberine is a promising candidate for future antidepressant therapies; however, no comprehensive systematic evaluation has been conducted to date. METHODS: Five electronic databases-PubMed, Embase, Web of Science, OVID, and the Cochrane Library-were systematically searched to identify preclinical studies investigating the antidepressant effects of berberine. Outcomes were assessed using the standardized mean difference with 95% confidence intervals to evaluate overall effect sizes. Study quality was evaluated using the 10-item Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Publication bias was assessed if more than 10 studies were included in an analysis. RESULTS: A total of 20 preclinical studies evaluating berberine's antidepressant effects were identified. Berberine administration was associated with reduced depression-like behaviors. Specifically, Berberine significantly: increased body weight (n = 7; SMD = 1.67; 95% CI: 0.57 to 2.76; P < 0.00001),Reduced immobility time in the tail suspension test (n = 9; SMD = -2.41; 95% CI: -3.15 to -1.67; P = 0.01),Increased sucrose consumption (n = 12; SMD = 1.82; 95% CI: 1.29 to 2.34; P = 0.02),Reduced immobility time in the forced swim test (n = 17; SMD = -2.35; 95% CI: -2.91 to -1.79; P < 0.00001),Increased total movement distance in the open field test (n = 7; SMD = 1.70; 95% CI: 0.58 to 2.81; P < 0.00001),Increased time spent in the open field test (n = 3; SMD = 1.02; 95% CI: 0.44 to 1.60; P = 0.92), Increased the number of crossings in the open field test (n = 4; SMD = 0.76; 95% CI: 0.20 to 1.33; P = 0.23). Furthermore, berberine was found to reduce levels of inflammatory markers, enhance neurotransmitter levels (excluding dopamine), and elevate brain-derived neurotrophic factor levels. CONCLUSION: Berberine consistently demonstrated antidepressant-like effects in preclinical models and showed preliminary potential mechanisms of action. However, the limitations of current studies highlight the necessity for more comprehensive preclinical research and well-designed clinical trials.