The modulatory influence of humic acid on cognitive impairment and neurobehavioral changes induced by colitis in adult male Wistar rats

Ulcerative colitis (UC) is a chronic inflammatory disorder that affects any part of the colon. UC often coexists with neuropsychiatric symptoms like anxiety, depression, and cognitive impairment. Current drugs for managing UC have adverse effects and are ineffective against these comorbid conditions. While recent studies suggest humic acid may offer novel benefits, there is a notable gap in the literature on its effects on colitis-induced neurobehavioral impairments. This study was conducted to investigate the role of humic acid (HA) in attenuating neurobehavioral disorders caused by dextran sulfate sodium–induced ulcerative colitis in male Wistar rats.

Twenty male Wistar rats were randomly assigned into groups (n = 5). Group 1 [control group]; group 2 [5% dextran sulfate sodium (DSS) without any additional treatment]; group 3 [5% DSS followed by administration of humic acid (30 mg/kg)]; group 4 [5% DSS followed by administration of sulfasalazine (200 mg/kg)]. The behavioral patterns of the rats were assessed pre-colitis induction, immediately after colitis induction on day 5, and immediately after drug treatment for ulcerative colitis (post-treatment). The disease activity index (DAI) for colitis was obtained on days 1, 3, 5, and 10 of the experimental duration. Thereafter, the brains were harvested for biochemical assays. Data were analyzed using ANOVA at p < 0.05.

Treatment with humic acid significantly attenuated anxiety, depression-like behavior, and cognitive impairment triggered by DSS-induced ulcerative colitis, with a decrease in the progression of DAI. A significant decrease in hippocampal and striatal MDA and nitrite levels, an increase antioxidant (SOD, catalase, GSH, and GST) levels, and a significant reduction in acetylcholinesterase (AChE) activity levels were also observed.

The present study demonstrates that humic acid suppresses the cognitive and behavioral changes caused by DSS-induced ulcerative colitis via its modulations of nitro-oxidative stress, inflammatory pathways, brain enzymatic antioxidants, and neurochemicals.