Oxidative stress is one of the major factors that contributes to brain deterioration in the elderly. Oxidation causes molecular alterations, structural damage, and brain dysfunction, which includes cognitive impairment. Memory loss can begin in middle-aged individuals, so prevention of brain deterioration before aging is important. Several studies have reported that curcumin and γ-oryzanol exhibits anti-oxidant and anti-inflammatory properties. However, curcumin and γ-oryzanol exhibit low aqueous solubility. Thus, a solid dispersion technique was used to prepare curcumin and γ-oryzanol to enhance their solubility and stability. This study aims to evaluate the effects and mechanisms of γ-oryzanol solid dispersion (GOSD) and curcumin solid dispersion (CURSD) on learning and memory in six groups of male rats (n=5/group). Group one was the adult control consisting of 6-week old male rats, and the remaining five groups consisted of 42-week (middle-aged) male rats. The groups were labeled as the control group, the GO group (GOSD 10 mg/kg•BW), the Cur group (CURSD 50 mg/kg•BW), the GO-LCur group (GOSD 10 mg/kg•BW plus CURSD 25 mg/kg•BW), and the GO-HCur group (GOSD 10 mg/kg•BW plus CURSD 50 mg/kg•BW). Substances were administrated by oral gavage once daily for 42 consecutive days. The GO-HCur group exhibited significantly increased learning and memory performance in a Morris water maze and in reacting to a spontaneous tendency novel object test. The rats also exhibited decreased levels of lipid peroxidation, increased superoxide dismutase levels, glutathione peroxidase levels, catalase activity, and enhanced c-Fos expression both in the hippocampus and prefrontal cortex. The results indicated that GOSD 10 mg/kg plus CURSD 50 mg/kg was able to enhance learning and memory performance in the middle-aged rats.
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