ArticleChinese journal of integrative medicine2025
Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.
Article in Chinese journal of integrative medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Transcriptional profiling reveals brain region-specific changes in gene expression induced by chronic unpredictable mild stress between stress-susceptible and stress-resilient mice.Psychopharmacology · 2026Article
- Citrus flavanones (naringenin, hesperidin, and hesperetin) in oral and gastric carcinogenesis: mechanistic insights into oxidative stress, cell death, epigenetic regulation, non-coding RNAs, and tumor microenvironment remodeling.Frontiers in cell and developmental biology · 2026Review
- Depression and Gastrointestinal Health Abnormalities: Treatment Approaches from the Perspective of Traditional Chinese Medicine.Neuropsychiatric disease and treatment · 2026Review
- Traditional Chinese Medicine Ameliorates Depression via the Gut-Brain Axis: A Review Focus on NLRP3/TLR4-Mediated Inflammatory Pathways and Gut Microbiota Modulation.Neuropsychiatric disease and treatment · 2026Review
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Authors and funding
10 authors.
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Abstract
objectivesTo determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.
methodsFifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.
resultsCompared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).
conclusionThe mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
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