Zingerone mitigates cognitive and motor impairments in a D-galactose-induced brain aging model: Role of oxidative stress and neuroinflammation.

BACKGROUND: The use of natural compounds with potent antioxidant and anti-inflammatory properties is a key strategy against age-related neurobehavioral deficits. This study investigated the protective effects of Zingerone (ZIN) and its underlying mechanisms against D-galactose (D-gal)-induced brain aging, with a focus on oxidative stress, inflammatory markers, and neurobehavioral deficits. MATERIAL AND METHODS: Male Wistar rats were divided into five groups: a control group (normal saline), a D-gal group (100 mg/kg), and three ZIN treatment groups (5, 10, and 20 mg/kg). An aging model was induced by daily subcutaneous injection of D-gal for eight weeks. Concurrently, the ZIN treatment groups received their respective doses by daily gavage over the same eight-week period. We evaluated the cognitive and locomotor functions of the animals using standard behavioral tests including Morris water maze (MWM), passive avoidance task (PAT), open field test (OFT) and rotarod test. In addition, we assessed the oxidative-antioxidative status and inflammatory conditions in the hippocampus, and conducted a qualitative histopathological evaluation of the hippocampal tissue and cortex of the experimental rats. RESULTS: Our findings indicate that ZIN treatment significantly enhanced cognitive and motor function and reduced oxidative stress and neuroinflammation in the hippocampus, as well as attenuate histopathological changes in the cortex and hippocampal areas of D-gal-induced brain aging rats. These effects were dose-dependent, and the most protective effects were demonstrated at the 20 mg/kg dosage. A significant association between oxidative stress markers, inflammatory cytokines, and cognitive functions was confirmed by correlation analyses. CONCLUSION: This study demonstrates that ZIN protects against D-gal-induced cognitive and motor deficits by enhancing antioxidant and anti-inflammatory activity in the hippocampus. These findings support the potential of ZIN as a natural compound with therapeutic and health benefits for improving age-related neurobehavioral decline.