Intranasal curcumin reduced anxio-depressive behaviors, oxidative stress, and downregulated NF-κB/NLRP3 inflammasome signaling in a rotenone-induced rat model of Parkinson's disease.

Supports targeting NLRP3/NF-κB-driven neuroinflammation and oxidative stress as therapeutically relevant mechanisms in PD and highlights intranasal curcumin as a potentially translational repurposing/delivery strategy, though the study lacks motor, dopaminergic neuron, and pharmacokinetic endpoints.

OBJECTIVE: To investigate the potential of intranasal curcumin (IN-CUCM) administration in alleviating anxio-depressive disorders in a rotenone (Rot)-induced Parkinson's disease (PD) rat model. METHODS: Adult male Wistar rats were administered Rot [3 mg/(kg·d)] for 14 d to induce PD and subsequently treated with IN-CUCM [2.5, 5, or 10 mg/(kg·d)] or fluoxetine [FLU, 10 mg/(kg·d)] for an additional 14 d (n=14 per group). Behavioral tests, including open field test, forced swimming test, and tail suspension test, were conducted to evaluate depression- and anxiety-like symptoms. The hippocampal (HPC) and prefrontal cortical (PFC) samples were analyzed for antioxidant enzymes (glutathione, catalase, and superoxide dismutase), oxidative stress (OS) markers (malondialdehyde and nitrite), and inflammatory mediators [nuclear factor kappa B (NF-κB), NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), caspase-1 (Casp-1), apoptosis-associated specklike protein (ASC), and cytokines] using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Molecular docking verification was also conducted. RESULTS: IN-CUCM [5 and 10 mg/(kg·d)] significantly ameliorated anxio-depressive-like behaviors of PD rats induced by Rot, and regulated OS biomarkers and endogenous antioxidants in both HPC and PFC (P<0.01). Additionally, IN-CUCM attenuated neuroinflammatory responses by downregulating NF-κB, ASC, NLRP3, and Casp-1, and modulating cytokines in these brain regions (P<0.01). Molecular docking analysis revealed a high affinity of CUCM for the NF-κB/NLRP3 inflammasome pathway. CONCLUSION: IN-CUCM effectively alleviates anxio-depressive-like behaviors in PD by mitigating OS and neuroinflammation.