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Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice.

ABSTRACT: We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improved exploratory activity, spatial learning, and recognition memory, respectively, in TRF-treated Tg mice. Brain metabolite profiling of wild-type and Tg mice treated with and without TRF was performed using ultrahigh performance liquid chromatography (UHPLC) coupled to high-resolution accurate mass (HRAM)-orbitrap tandem mass spectrometry (MS/MS). Metabolic pathway analysis found perturbed metabolic pathways that linked to AD. TRF treatment partly ameliorated metabolic perturbations in Tg mouse hippocampus. The mechanism of this pre-emptive activity may occur via modulation of metabolic pathways dependent on Aβ interaction or independent of Aβ interaction.

SUBMITTER: Durani LW

PROVIDER: S-EPMC6004929 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice.

Durani Lina Wati LW Hamezah Hamizah Shahirah HS Ibrahim Nor Faeizah NF Yanagisawa Daijiro D Nasaruddin Muhammad Luqman ML Mori Masaki M Azizan Kamalrul Azlan KA Damanhuri Hanafi Ahmad HA Makpol Suzana S Wan Ngah Wan Zurinah WZ Tooyama Ikuo I

Journal of Alzheimer's disease : JAD 20180101 1

We have recently shown that the tocotrienol-rich fraction (TRF) of palm oil, a mixture of vitamin E analogs, improves amyloid pathology in vitro and in vivo. However, precise mechanisms remain unknown. In this study, we examined the effects of long-term (10 months) TRF treatment on behavioral impairments and brain metabolites in (15 months old) AβPP/PS1 double transgenic (Tg) Alzheimer's disease (AD) mice. The open field test, Morris water maze, and novel object recognition tasks revealed improv ...[more]

PMID: 29889072

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Project description:BACKGROUND:Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed. METHODS:The protocol for this systematic review was registered in "PROSPERO" (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including ("Palm Oil"[Mesh]) AND "Nervous System"[Mesh], ("Palm Oil"[Mesh]) AND "Neurodegenerative Diseases"[Mesh], ("Palm Oil"[Mesh]) AND "Brain"[Mesh], and ("Palm Oil"[Mesh]) AND "Cognition"[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator. RESULTS:All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and ?-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer's disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of ?-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with ?-tocotrienols and neurotoxins improved the redox status in neuronal cells better than ?- and ?-tocotrienols. Both pre-treatment and post-treatment with ?-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses. CONCLUSIONS:Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and ?-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and ?-tocotrienol exerted prophylactic neuroprotective effects, while ?-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of ?- and ?-tocotrienol isomers.

Dataset Information

Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice.

Publications

Tocotrienol-Rich Fraction of Palm Oil Improves Behavioral Impairments and Regulates Metabolic Pathways in AβPP/PS1 Mice.

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