Obesity-diabetes syndrome poses a considerable risk for mild cognitive impairment (MCI). Our study was designed to explore therapeutic potential of γ-oryzanol (Orz), a brown rice-specific oil composed of ferulic acid ester with several phytosterols, on MCI in high-fat diet (HFD) induced obese aged mice. After being housed on an HFD for 4 months, regular Orz or the nanoparticulated form of Orz (Nano-Orz), which markedly enhances its intestinal absorption, was administered to aged mice. Mice treated with regular Orz for 4 months exhibited significant improvement in spatial cognitive function. Impressively, mice treated with Nano-Orz demonstrated cognitive improvement as early as 1 month, with substantial recovery by 3 months. In the hippocampus, treatment with both regular Orz and Nano-Orz upregulated genes associated with neurogenesis and stem cell function accompanied by a significant increase in gene expressions of anti-inflammatory cytokines. Our data highlight a therapeutic potential of Orz for obesity-associated MCI.

Brown rice bran fermented with Aspergillus oryzae (FBRA), produced via fermentation of rice bran with the specific fungus, has antioxidant and anti-inflammatory properties in murine models. Because oxidative stress and neuroinflammation are critical in the brain aging and cognitive impairment, we hypothesized that FBRA would improve cognitive function. We explored the impact of FBRA on cognitive impairment in mice focusing on cognitive behaviors and the profile of hippocampal gene expression. Twenty-week-old male C57BL/6J mice were divided into four groups: lab chow (LCD), LCD+FBRA, high fat diet (HFD), and HFD+FBRA. After fifty weeks, cognitive function was examined by two behavioral tests. FBRA administration significantly improved cognitive function under both LCD and HFD conditions. Hippocampal microarray analyses revealed that expression levels of immediate early genes including Egr1 and Nr4a1 were exclusively increased in LCD+FBRA compared to LCD. These findings raise a possibility that FBRA improves cognitive function in aged mice at least partly by modulating hippocampal gene expression.