Akademik Veri Yönetim Sistemi
European Journal of Pharmacology, cilt.1011, 2026 (SCI-Expanded, Scopus)
Cognitive disorders and neurodegenerative diseases are increasing in individuals with type 2 diabetes mellitus (T2DM), yet the underlying mechanisms and effective treatments remain underexplored. This study uniquely evaluates the effects of thymoquinone on T2DM-related cognitive dysfunctions. The neuroprotective and antidiabetic effects of thymoquinone were examined using a T2DM model induced by streptozotocin/nicotinamide. Forty rats were divided into five groups: Control (CTRL), Type 2 Diabetes Mellitus (T2DM), CTRL + Thymoquinone (T), T2DM + Thymoquinone (T2DM + T), and T2DM + Metformin (T2DM + M). Treatments began one-week post-induction, with weekly monitoring of blood glucose and body weight. After conducting the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT), behavioural assessments were performed, including the open field test (OFT), novel object recognition test (NORT), passive avoidance test (PAT), and Morris’ water maze test (MWMT). Antioxidant parameters were analysed in pancreas and brain tissues, which were also examined histologically. Key metabolites—tryptophan, kynurenine, and kynurenic acid—were quantified using ELISA to investigate the modulation of the tryptophan-kynurenine pathway. Our findings provide novel evidence that thymoquinone offers dual therapeutic benefits for systemic and central T2DM complications. It improves glycaemic control and β-cell function in the pancreas, while enhancing cognitive function and reducing oxidative stress in the brain. These effects are likely mediated through modulation of kynurenine pathway metabolites. This innovative approach suggests that thymoquinone holds potential as a therapeutic option for addressing cognitive impairments associated with T2DM, offering mechanistic insights that advance current understanding beyond the existing literature.