On Anxiolytic and Antidepressant Effects of Curcumin in Sepsis-Induced Post-Intensive Care Syndrome: Antioxidant and Anti-Inflammatory Effects.

Introduction: Post-intensive care syndrome (PICS) encompasses a range of physical, cognitive, and mental impairments frequently observed in individuals who have undergone intensive care unit treatment. This study aimed to investigate the potential of curcumin (CuC) in mitigating anxiety- and depressive-like behaviors associated with sepsis-induced PICS in mice.

Methods: To establish a PICS model, male C57/B6 mice were subjected to sublethal cecal slurry (CS) injection to induce sepsis. The mice were orally administered CuC at doses of 10, 25, and 50 mg/kg, respectively, or fluoxetine at a dose of 10 mg/kg for a duration of 3 weeks. Anxiety and depression were assessed using the open field test, tail suspension test, and forced swimming test. At the end of the study, the mice were sacrificed, and their hippocampi (HC) were isolated for molecular analyses.

Results: The behavioral tests revealed anxiety- and depressive-like behaviors in the CS-exposed animals. CuC at 25 and 50 mg/kg, but not 10 mg/kg, mitigated anxiety- and depressive-like behaviors in sepsis-induced PICS mice. Additionally, upregulation of NF-κB, NLRP3, Caspase 1, and ASC genes and protein levels of IL1β, IL6, IL18, and TNFα were observed in the HC of CS-exposed animals. Furthermore, the hippocampal concentrations of oxidative stress biomarkers, including glutathione peroxidase, superoxide dismutase, and malondialdehyde, were found to be dysregulated.

Conclusion: The administration of CuC demonstrated the ability to reverse the detrimental effects of CS. The modulation of immune response by CuC underscores its potential as an antidepressant and protective agent against sepsis-induced PICS, suggesting its viability as a potential therapeutic tool for sepsis treatment.