Crocin attenuates the lipopolysaccharide-induced neuroinflammation via expression of AIM2 and NLRP1 inflammasome in an experimental model of Parkinson's disease.

The underlying mechanisms of inflammasome activation and the following dopaminergic neuron loss caused by chronic neuroinflammation remain entirely unclear. Therefore, this study aimed to investigate the impact of crocin on the inflammasome complex within an experimental model of Parkinson's disease (PD) using male Wistar rats. PD was induced by the stereotaxic injection of lipopolysaccharide (LPS), and crocin was intraperitoneally administrated one week before the lesion, and then treatment continued for 21 days. Open field (OF) and elevated plus maze tests were applied for behavioral assays. Furthermore, hematoxylin and eosin (H&E) and immunostaining were performed on whole brain tissue, while dissected substantia nigra (SN) was used for immunoblotting and real-time PCR to evaluate compartments involved in PD. The time spent in the center of test was diminished in the LPS group, while treatment with 30 mg/kg of crocin significantly increased it. H&E staining showed a significant increase in cell infiltration at the site of LPS injection, which was ameliorated upon crocin treatment. Notably, crocin-treated animals showed a reduced number of caspase-1 and IL-1β positive cells, whereas the number of positive cells was increased in the LPS group ( < 0.05). A significant decrease in tyrosine hydroxylase (TH) expression was also found in the LPS group, while crocin treatment significantly elevated its expression. IL-1β, IL-18, NLRP1, and AIM2 genes expression significantly increased in the LPS group. On the other hand, treatment with 30 mg/kg of crocin significantly downregulated the expression levels of these genes along with NLRP1 ( < 0.05). In summary, our findings suggest that crocin reduces neuroinflammation in PD by diminishing IL-1β and caspase-1 levels, potentially by inhibiting the expression of AIM2 and NLRP1 genes.