SynthesisFrontiers in pharmacology2026
Antidepressant effects and therapeutic potential of naringenin: a systematic review and meta-analysis of preclinical studies.
Synthesis in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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6 authors.
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Abstract
Background: The prevalence of depression has increased steadily over recent decades, making it a major global public health concern. Although currently available pharmacotherapies demonstrate therapeutic efficacy, their clinical utility is often limited by adverse effects. Naringenin, a naturally occurring flavonoid compound, has shown potential antidepressant-like effects in preclinical studies. However, no comprehensive meta-analysis has yet systematically evaluated its efficacy in animal models of depression. Objective: This study aimed to systematically assess the antidepressant-like effects of naringenin in animal models of depression through a systematic review and meta-analysis, and to further elucidate its underlying mechanisms of action. Methods: A systematic literature search was conducted across five electronic databases (Embase, Web of Science, PubMed, Cochrane Library, and OVID) from database inception to November 2025. Methodological quality was assessed using the SYRCLE risk of bias tool. Data synthesis and statistical analyses were performed using Review Manager 5.4. Results: A total of 13 studies involving 212 rats were included. Meta-analysis demonstrated that, compared with the control group, naringenin treatment significantly reduced immobility time in the forced swimming test (FST)[SMD = -4.66; 95% CI (-6.55, -2.76); P < 0.00001] and tail suspension test (TST) [SMD = -5.36; 95% CI (-7.37, -3.36); P < 0.0001], increased the number of crossings in the open field test (OFT) [SMD = 2.18; 95% CI (0.52, 3.85); P= 0.01], and elevated sucrose consumption [SMD = 4.18; 95% CI (2.66, 5.71); P <0.00001]. Furthermore, naringenin reduced levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), restored norepinephrine (NE) and serotonin (5-HT) concentrations, increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels, decreased malondialdehyde (MDA) and nitrite (NIT) levels, upregulated brain-derived neurotrophic factor (BDNF) expression, and lowered serum corticosterone(CORT) levels. Although heterogeneity was observed in behavioral outcomes, sensitivity analyses confirmed the robustness of the pooled results. Conclusion: Naringenin ameliorates depressive-like behaviors in rats, potentially through anti-inflammatory effects, modulation of neurotransmitter levels, and attenuation of oxidative stress. Nevertheless, all current evidence is derived from animal experiments. High-quality human clinical trials are needed in the future to evaluate its therapeutic efficacy.
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