Curcumin modulates oxidative stress, cortical activity and corticosterone in mice exposed to chronic social stress in the spontaneous aggressiveness model

Stress constitutes a fundamental physiological mechanism essential for survival and environmental adaptation. Chronic social stress is a major risk factor for emotional and behavioral disturbances, including aggressiveness. Curcumin, a bioactive polyphenol derived from Curcuma longa, exhibits antioxidants, anti-inflammatory, and antidepressant properties, making it a promising neuroprotective agent. Previous studies using the Spontaneous Aggressiveness Model (MSA) demonstrated increased production of reactive oxygen species (ROS) and c-Fos expression in aggressive mice, suggesting a role for oxidative stress. This study investigated the effects of curcumin supplementation on neuroendocrine and oxidative parameters in male Swiss Webster mice subjected to chronic social stress in MSA. Animals (n = 60, 3 weeks old) were allocated to control and curcumin-treated groups. The treated group received a 1.5% curcumin-enriched diet for ten days before social regrouping in week 10. Behavioral categorization into non-regrouped (NR), aggressive (AgR), subordinate (Sub), and harmonious (Har) profiles were performed at week 16. Plasma corticosterone was quantified by ELISA, ROS production by DHE assay, and c-Fos expression by immunofluorescence. All procedures were approved by the Ethics Committee on Animal Use of the Oswaldo Cruz Institute (CEUA/IOC L-022/2025). Curcumin supplementation reduced attack intensity, prevented hypercortisolemia in NR mice, and decreased ROS levels in aggressive animals, supporting its antioxidant and neuroendocrine modulatory effects as a potential neuroprotective strategy under chronic social stress.