Diosgenin Alleviates Inflammation in the Colon and Hippocampus and PartlyAttenuates Comorbid Autistic-like Behaviors in Experimental Colitis in Mice

INTRODUCTION: Inflammatory bowel disease (IBD) is comorbid with behavioral disorders like autism spectrum disorder (ASD). Neuroinflammation is involved in the pathophysiology of ASD. Diosgenin has pharmacological properties. We aimed to assess the potential properties of diosgenin in mitigating comorbid autistic-like behaviors with colitis in mice, focusing on its probable effects on the neuroinflammatory response in the hippocampus. METHODS: Colitis was induced using acetic acid. Forty male mice were divided into five groups and treated intraperitoneally for seven continuous days with 0.9% saline containing Tween 20 at a concentration of 2% (10 ml/kg) or diosgenin (25, 50, and 100 mg/ kg). Behavioral tests, including sociability and social preference indexes, passive avoidance memory, and aggressive-like behaviors, were assessed. Then, the colon and hippocampus were dissected out. A microscopic evaluation of the colon was done. RT-PCR measured TLR4, TNF-α, IL-1β, and NLRP3 gene expression in the hippocampus and colon. RESULTS: Colitis is associated with histopathological alterations in the colon and an increase in the gene expression of inflammatory mediators in the colon. Colitis reduced sociability and social preference indexes, impaired passive avoidance memory, and increased aggressive-like behaviors. These behaviors are accompanied by increased gene expression of inflammatory mediators in the hippocampus. Diosgenin mitigated the negative effects of colitis on the hippocampus and colon. DISCUSSION: Diosgenin attenuated inflammatory responses in the colon, autistic-like behaviors, and expression of genes relevant to neuroinflammation in the hippocampus following colitis. CONCLUSION: Diosgenin likely alleviated autistic-like behaviors following colitis, possibly through the reduction of inflammatory gene expressions in the hippocampus.