Indole-3-Carbinol Selectively Prevents Chronic Stress-Induced Depression-but not Anxiety-Like Behaviors via Suppressing Pro-Inflammatory Cytokine Production and Oxido-Nitrosative Stress in the Brain

Abstract

Indole-3-carbinol (I3C), a phytochemical enriched in most cruciferous vegetables, has been shown to display various biological activities such as anti-oxidative stress, anti-inflammation, and anti-carcinogenesis. In this study, we investigated the regulatory effect of I3C on chronic stress-induced behavioral abnormalities in mice. Results showed that repeated I3C treatment at the dose of 10, 30, and 60 mg/kg prevented chronic social defeat stress (CSDS)-induced behavioral abnormalities in the tail suspension test, forced swimming test, sucrose preference test, and social interaction test in mice, and did not affect CSDS-induced behavioral abnormalities in the elevated plus maze, light-dark test, and open-field test, suggesting that the I3C treatment selectively prevents the onset of depression- but not anxiety-like behaviors in chronically stressed mice. Further analysis demonstrated that repeated I3C treatment (60 mg/kg, 10 days) prevented CSDS-induced increases in levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA and protein, but did not affect CSDS-induced decreases in levels of IL-4, IL-10, and Ym-1 mRNA and/or protein in the hippocampus and prefrontal cortex, suggesting that I3C can selectively prevent chronic stress-induced pro-inflammatory but not anti-inflammatory responses in the brain. Further analysis showed that repeated I3C treatment (60 mg/kg, 10 days) prevented CSDS-induced increases in levels of nitrite and malondialdehyde (MDA), decreases in contents of glutathione (GSH), and decreases in levels of brain derived neurotrophic factor (BDNF) protein in the hippocampus and prefrontal cortex. These results demonstrated that I3C selectively prevents chronic stress-induced depression-like behaviors in mice likely through suppressing neuroinflammation and oxido-nitrosative stress in the brain.

The relationship between serum Resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder

“…The reduction was even more signi cant in adolescent depression with suicidal ideation/behavior (51). IL-4, a type of Th2 cytokines with anti-in ammatory effects, has been widely reported to have a protective effect on depression in pre-clinical studies (52,53). In studies of adult depression, more evidence has also been informed of elevated levels of IL-4 in peripheral blood (54,55).…”

Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases

“…However, the antinociceptive mechanism of I3C needs to be further investigated. I3C treatment prevented chronic social defeat stress (CSDS), induced behavioral abnormalities, and ameliorated depression‐like behavior, but not anxiety‐like behavior via a decrease in brain‐derived neurotrophic factors (BDNF) levels, inflammation, and oxidative stress in the hippocampus and prefrontal cortex (Pan et al, 2022). Most of the above‐mentioned protective activities of I3C were reported following oral administration.…”