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The Effect of Oil Palm Phenolics (OPP) on Urinary Metabolomic Profile in Atherogenic Diet Induced Rat Model of Alzheimer's Disease (AD)

Alzheimer's disease (AD) is a neurodegenerative disorder, estimated to strike more than 4.7 million individuals older than 65 in the USA. Since oxidative stress is a key component driving AD, we hypothesized that OPP, a water soluble fraction extracted from oil palm fruit rich in phenolics with high antioxidant activity, may attenuate its progression. In this study, we used the metabolomic approach to investigate the effect of OPP on change in metabolism produced in high cholesterol diet induced model for AD. Thirty two male Brown Norway rats were randomly assigned to 4 groups: the isocaloric control diet (C), high cholesterol (2% cholesterol) (H), high cholesterol + OPP (5% OPP) (HP) and high cholesterol + curcumin (2% curcumin) (HC). Urine samples were collected once a month for 6 months. Water maze was performed monthly to evaluate cognitive behavior. β‐amyloid was measured at termination of study as a marker for AD using ELISA. Curcumin, a dietary polyphenolic compound has been shown to have benefit in AD and was used as a positive control. Proton nuclear magnetic resonance (1H NMR) spectra, acquired using 500 MHz magnet were processed using ACD labs software. The processed, digitized NMR spectral data was subjected to multivariate data analysis (SIMCA P+). Principal component analysis (PCA) and partial least squares‐discriminant analysis (PLS‐DA) score plots showed clear separation among all four groups indicating differences in their metabolomics profiles. OPLS regression analysis gave significant correlations between the urinary metabolomic profiles and escape latency using water maze (R2=0.78) and the β amyloid burden (R2=0.73). The metabolites responsible for the differences in the metabolomic profile between different groups were quantified using CHENOMX NMR metabolite database. Some metabolites from the tryptophan‐kynurenine‐quinolinic pathway were significantly higher in the cholesterol fed animals (H) as compared to the control (C). Treatment with curcumin (HC) or OPP (HP) brought down the concentration of these metabolites significantly and closer to the control levels. This pathway has been shown to be perturbed in neurodegenerative diseases. Taken together, our data indicates that dietary OPP or curcumin have potential benefit in AD. In addition, specific urinary metabolites may serve as non‐invasive biomarkers for progression of neurodegenerative diseases including AD.