Abstract
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor known to play a critical role in regulating neuroinflammation and neurodegenerative processes, including Alzheimer's disease. Prior studies from our group demonstrated that rice bran extract (RBE) enhances cognitive function and increases PPARγ DNA-binding activity in the brain, effects that were abolished by PPARγ antagonism. These findings suggest that bioactive constituents within RBE may modulate PPARγ signaling. The current study aimed to provide additional evidence for the involvement of PPARγ activation in the neuroprotective effects of RBE and to identify key RBE-derived components that may contribute to these effects. METHODS: A neuroinflammatory mouse model was treated orally for 21 consecutive days with RBE. The brain CD36 and amyloid-beta (Aβ) protein levels were measured. HPLC and GC were used to assess the levels of RBE components. To measure alterations in fatty acid content after treatment with RBE, brain levels of DHA, EPA and AA were assessed using UHPLC/MS-MS. RESULTS: RBE treatment increased the brain levels of CD36, the direct PPARγ target, and decreased Aβ levels. A strong correlation was detected between the Aβ and CD36 protein levels. As RBE was found to be rich in linolenic acid (ALA), linoleic acid (LA) and oleic acid, their metabolites concentrations in mice brain were measured, and results indicated higher concentration of EPA and DHA after RBE treatment. CONCLUSIONS: RBE exerts neuroprotective effects potentially through activation of the PPARγ pathway, as evidenced by CD36 upregulation and Aβ reduction. The enrichment of RBE in polyunsaturated fatty acids (PUFAs), along with the observed increase in their brain-penetrant metabolites (EPA and DHA), suggests these lipids may contribute to the cognitive benefits of RBE.