The effect of safranal on anxiety and the MYD88/NF-kb signaling pathway in the hippocampus in a rat model of ulcerative colitis.

Introduction: Individuals with colitis are more likely to experience anxiety symptoms compared to those without the condition. However, the biological mechanisms linking colitis to anxiety remain unclear. This study investigated the potential effects of safranal on anxiety-like behaviors and the involvement of the MYD88/NF-κB signaling cascade within the hippocampus in a rat model of ulcerative colitis induced by acetic acid. Methods: Thirty-two male rats were randomly divided into four groups: a control group, a colitis group, and two treatment groups receiving safranal at 72.75 or 145.5 mg/kg. The intervention lasted seven days. To confirm colitis induction, the Disease Activity Index (DAI) was assessed based on weight loss, stool consistency, and presence of blood. Anxiety-like behaviors were evaluated using the open field test and elevated plus maze. Molecular analyses measured hippocampal expression of TLR4, MYD88, and NF-κB, along with IL-6 and IL-1β protein levels. Results: Safranal administration alleviated anxiety-like behaviors, as reflected by improved performance in both behavioral tests. Colitis induction was confirmed by a significant elevation in the DAI score, while safranal treatment at both doses significantly reduced this score, indicating attenuation of colitis severity. Safranal also decreased hippocampal IL-1β and IL-6 levels and suppressed TLR4, MYD88, and NF-κB expression, demonstrating inhibition of neuroinflammatory signaling. Conclusions: These findings suggest that safranal exerts anxiolytic effects in experimental colitis, likely mediated through downregulation of the TLR4/MYD88/NF-κB pathway and reduced hippocampal neuroinflammation.