Grape Seed Extract Mitigates Acute Stress-Induced Neuroinflammation and Oxidative Damage in Female Mice: Evidence for Gut–Brain Axis Modulation
- 1Technology Development Center, Biotechnology Unit, Neurobiotechnology Research Group, Federal University of Pelotas, Pelotas, RS Brazil
- 2Oxidative Stress & Antioxidants Laboratory, Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, RS Brazil
- 3Technology Development Center, Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Federal University of Pelotas, Pelotas, RS Brazil
Abstract
Short-term stress is known to trigger oxidative and neuroinflammatory responses that contribute to the onset and progression of major depressive disorder (MDD). Phenolic compounds, such as grape seed extract (GSE), have gained attention for their ability to modulate these biological pathways. This study aimed to evaluate whether GSE (20 or 40 mg/kg, oral route) exerts antidepressant-like effects and mitigates stress-induced biochemical alterations in female mice exposed to the acute restraint stress (ARS) model. Female mice were pretreated with GSE and subsequently subjected to ARS. Behavioral outcomes were assessed using the tail suspension test (TST) and open field test (OFT). Plasma corticosterone levels, reactive species (RS) production in the prefrontal cortex, hippocampi, and small intestine, and mRNA expression of inflammatory mediators (NF-κB, IL-1β, IFN-γ) in brain and gut tissues were quantified through standard biochemical and molecular analyses. GSE pretreatment significantly prevented the ARS-induced increase in immobility time in the TST, without affecting locomotor activity in the OFT. ARS exposure elevated corticosterone concentrations and RS generation across central and peripheral tissues; both effects were attenuated by GSE. Additionally, GSE downregulated stress-induced expression of pro-inflammatory cytokines in neural and intestinal samples, indicating suppression of key inflammatory pathways. These findings demonstrate that GSE exerts antidepressant-like, antioxidant, and anti-inflammatory effects through interconnected redox and cytokine signaling pathways, as summarized in the Graphical Abstract. Importantly, this study provides novel evidence that GSE acts along the gut–brain axis, mitigating corticosterone-driven oxidative and inflammatory responses. These results highlight GSE as a promising natural compound for the prevention and management of stress-related neuropsychiatric disorders.
Graphical Abstract: Graphical abstract summarizing the antidepressant-like, antioxidant, and anti-inflammatory effects of grape seed extract (GSE) in mice subjected to acute restraint stress (ARS)
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BibTeX
@article{xavier2026grape,
title = {{Grape Seed Extract Mitigates Acute Stress-Induced Neuroinflammation and Oxidative Damage in Female Mice: Evidence for Gut–Brain Axis Modulation}},
author = {Rafaela Xavier and Marina Rigotti and Renata L. De Oliveira and Laura F. Finger and Lauren N. Pujol and Fernanda S. S. Sousa and Suzana L. Lanius and Tiago V. Collares and Fabiana K. Seixas and Catia S. Branco and Lucielli Savegnago},
journal = {Neurochemical Research},
year = {2026},
month = oct,
doi = {10.1007/s11064-026-04939-9},
url = {https://doi.org/10.1007/s11064-026-04939-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Grape Seed Extract Mitigates Acute Stress-Induced Neuroinflammation and Oxidative Damage in Female Mice: Evidence for Gut–Brain Axis Modulation
AU - Rafaela Xavier
AU - Marina Rigotti
AU - Renata L. De Oliveira
AU - Laura F. Finger
AU - Lauren N. Pujol
AU - Fernanda S. S. Sousa
AU - Suzana L. Lanius
AU - Tiago V. Collares
AU - Fabiana K. Seixas
AU - Catia S. Branco
AU - Lucielli Savegnago
PY - 2026
DA - 2026/10/27
JO - Neurochemical Research
DO - 10.1007/s11064-026-04939-9
UR - https://doi.org/10.1007/s11064-026-04939-9
AB - Short-term stress is known to trigger oxidative and neuroinflammatory responses that contribute to the onset and progression of major depressive disorder (MDD). Phenolic compounds, such as grape seed extract (GSE), have gained attention for their ability to modulate these biological pathways. This study aimed to evaluate whether GSE (20 or 40 mg/kg, oral route) exerts antidepressant-like effects and mitigates stress-induced biochemical alterations in female mice exposed to the acute restraint stress (ARS) model. Female mice were pretreated with GSE and subsequently subjected to ARS. Behavioral outcomes were assessed using the tail suspension test (TST) and open field test (OFT). Plasma corticosterone levels, reactive species (RS) production in the prefrontal cortex, hippocampi, and small intestine, and mRNA expression of inflammatory mediators (NF-κB, IL-1β, IFN-γ) in brain and gut tissues were quantified through standard biochemical and molecular analyses. GSE pretreatment significantly prevented the ARS-induced increase in immobility time in the TST, without affecting locomotor activity in the OFT. ARS exposure elevated corticosterone concentrations and RS generation across central and peripheral tissues; both effects were attenuated by GSE. Additionally, GSE downregulated stress-induced expression of pro-inflammatory cytokines in neural and intestinal samples, indicating suppression of key inflammatory pathways. These findings demonstrate that GSE exerts antidepressant-like, antioxidant, and anti-inflammatory effects through interconnected redox and cytokine signaling pathways, as summarized in the Graphical Abstract. Importantly, this study provides novel evidence that GSE acts along the gut–brain axis, mitigating corticosterone-driven oxidative and inflammatory responses. These results highlight GSE as a promising natural compound for the prevention and management of stress-related neuropsychiatric disorders. Graphical Abstract: Graphical abstract summarizing the antidepressant-like, antioxidant, and anti-inflammatory effects of grape seed extract (GSE) in mice subjected to acute restraint stress (ARS)
SN - 0364-3190
SN - 1573-6903
ER -