Zingerone Attenuates Cadmium-Induced Neuroinflammation, Oxidative Stress and Cognitive Deficit on the Prefrontal Cortex of Adult Wistar Rats

Augustine Oviosun,1 Ezinne Chidinma Oviosun,2 Nto Johnson Nto,3– 5 Adejoke Elizabeth Memudu,6 Emeka Godson Anyanwu1,3 1Department of Anatomy, Faculty of Biomedical Sciences, Kampala International University, Western Campus, Ishaka-Bushenyi, Uganda; 2Department of Anatomy, Faculty of Basic Medical Sciences, Ambrose Alli University, Ekpoma, Edo State, Nigeria; 3Department of Anatomy, Faculty of Basic Medical Sciences, University of Nigeria, Enugu Campus, Enugu, Nigeria; 4Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; 5South African Medical Research Council/Stellenbosch University, Genomics of Brain Disorders Extramural Unit, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa; 6Department of Anatomy, Faculty of Basic Medical Sciences, Edo State University, Uzairue, Edo State, NigeriaCorrespondence: Augustine Oviosun, Email [email protected]/Background: Exposure to heavy metals like cadmium can adversely affect our brain function and cognitive abilities. Scientific evidence has strongly linked cadmium exposure to neurotoxicity, including oxidative damage and neuroinflammation. This study investigated the therapeutic role of Zingerone on cadmium-induced inflammation, oxidative stress and cognitive decline in the prefrontal cortex.Methodology: Thirty adult male Wistar rats were randomly assigned to six groups of five rats each. Group A (Control group), Group B (5mg/kg of cadmium induction), Group C (100mg/kg of Zingerone only), Group D-F (Treatment groups: 5mg/kg of cadmium+50mg/kg,100mg/kg, 200mg/kg of Zingerone respectively). To determine the cognitive abilities, we used a novel object recognition test (NORT), the whole treatment lasted for 21 days. We used blood samples and brain tissue for histological, biochemical and immunohistochemical evaluations. Data from this study was analysed using GraphPad Prism 10, and statistical difference between groups was determined using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05).Result and discussion: There was significant reduction in superoxide dismutase (SOD), catalase (CAT) and significant increase malondialdehyde (MDA) in the cadmium-only group; however, this effect was mitigated in Groups C–F that received zingerone treatment. Cadmium exposure resulted in elevated levels of inflammatory cytokine Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α), these increases were significantly reduced in all Zingerone-treated groups. Zingerone considerably improved cognitive function, as seen by significant improvements in the discrimination index and novel object recognition time. Also, Zingerone significantly mitigated the over-expressivity of astrocytes in the prefrontal cortex and improved the histoarchitecture of the prefrontal cortex.Conclusion: This study shows that zingerone demonstrated anti-oxidative and anti-inflammatory abilities and enhanced cognitive performance. These results indicate that zingerone might be a useful therapeutic agent that can mitigate neuroinflammation, oxidative damage, and cognitive decline.Keywords: astrocytosis, neuroinflammation, oxidative stress, cognitive impairment, zingerone, cadmium