Nano-Curcumin improves caffeine-induced cerebral alterations in male Wistar rats by modifying oxidative stress, inflammation, and COX-2/NF-κB/Nrf2 signaling

Abstract Background This research aims to determine the probable protective effect of nano-curcumin (N-CUR) on caffeine (1,3,7-trimethylxanthine)-induced neurotoxicity in cerebral rats. Methods Twenty-four male Wistar rats were divided into three groups: control, caffeine (150 mg kg −1 ), and caffeine (150 mg kg −1 ) treated with N-CUR (300 mg kg −1 ). All treatments were administrated by gavage every day for a month. Results Administration of caffeine significantly elevated the levels of serum interleukins 6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and cyclooxygenase2 (COX-2). Also, there was a significant increase in levels of cerebral malondialdehyde (MDA), significantly diminished glutathione (GSH), and superoxide dismutase (SOD) activity. Caffeine administration significantly downregulated the gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB). Administration of N-CUR caused a significant amelioration in TNF-α and IL-6 levels and a significant rise in SOD activity, while it caused a significant downregulation in NF-κB mRNA expression. Additionally, N-CUR has exerted insignificant amelioration of COX-2 and MDA contents and Nrf2 mRNA expression compared to the caffeine-treated group. Conclusion N-CUR may have a mild to moderate ameliorative effect on caffeine-induced apoptosis, oxidative stress, and inflammatory response in the cerebrum.