Abstract Diabetes mellitus (DM) is a global disease that directly affects many organs, including the brain and cerebellum. This study aims to evaluate the effects of zingerone (ZO) on neurotoxicity, a prevalent consequence of DM. Female Sprague–Dawley rats ( n = 60) were divided into 6 groups. Experimental groups were established as Control, DM, DM + Metformin (MET), DM + ZO25, DM + ZO50, and ZO50. At the end of 28 days, the brain and cerebellum tissues were used for the analyses. To evaluate oxidative stress and oxidative DNA damage, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and glutathione reductase (GR) levels were measured. Apoptosis was assessed by determining Caspase-3 expression levels. In addition, H2A.X, NeuN, and glial fibrillary acidic protein (GFAP) expression levels were analyzed to evaluate DNA damage, neuronal integrity, and glial activation, respectively.While nNOS, 8-OHdG, Caspase-3, H2A.X, NeuN, GFAP, MDA, and iNOS levels increased in the DM group, it was observed that tissue damage decreased in a dose-dependent manner in the ZO treatment groups. Also, while there was a decrease in SOD and GR activity and GSH levels in the DM group, ZO 50 mg/kg treatment caused an increase in these enzymes. This study suggests that ZO may exert neuroprotective effects by mitigating oxidative stress, suppressing inflammation, and modulating apoptosis in diabetes-induced neurotoxicity. Graphical Abstract
ORNEK et al. (2026) studied this question.