Neuroinflammation in hypothyroidism? Chrysin treatment as a strategy to reduce neuroinflammation induced by hypothyroidism.

This study investigates the intricate relationship between neuroinflammation and adult-onset hypothyroidism, exploring the potential therapeutic role of chrysin, a flavonoid known for its beneficial effects on neuroinflammatory modulation. Hypothyroidism was induced in female C57BL/6 mice using a 0.1 % methimazole (MTZ) treatment in drinking water for 31 days. After confirming reduced thyroid hormone levels, mice received either a vehicle or chrysin (20 mg/kg) via intragastric delivery once daily for 28 consecutive days. Brain samples from the hippocampus and prefrontal cortex were collected for ex vivo analysis, including western blot and ELISA assays for inflammation-related proteins. Our findings reveal significant neuroinflammation associated with hypothyroidism, particularly in the hippocampus, involving the activation of NLRP3, NF-κB, and p38 MAPK pathways, leading to the synthesis of pro-inflammatory interleukins. Chrysin treatment effectively mitigated this neuroinflammation, suggesting its promise as a therapeutic intervention. Furthermore, our study elucidates a potential mechanistic pathway initiated by reduced thyroid hormones, which possible alterations in toll-like receptor (TLR) signaling, subsequently upregulating NLRP3, NF-κB, and p38 MAPK. Chrysin inhibits this pathway, ultimately reducing pro-inflammatory cytokines, in both hippocampi and prefrontal cortex tissues. This research provides valuable insights into the neuroinflammatory consequences of hypothyroidism and positions chrysin for repositioning as a potential natural therapeutic compound against hypothyroidism-induced neuroinflammation.