title: Oligomerised lychee fruit-derived polyphenol attenuates cognitive impairment in senescence-accelerated mice and endoplasmic reticulum stress in neuronal cells.
abstract: Recently, the ability of polyphenols to reduce the risk of dementia and Alzheimer's disease (AD) has attracted a great deal of interest. In the present study, we investigated the attenuating effects of oligomerised lychee fruit-derived polyphenol (OLFP, also called Oligonol) on early cognitive impairment. Male senescence-accelerated mouse prone 8 (SAMP8) mice (4 months old) were given OLFP (100 mg/kg per d) for 2 months, and then conditioned fear memory testing was conducted. Contextual fear memory, which is considered hippocampus-dependent memory, was significantly impaired in SAMP8 mice compared with non-senescence-accelerated mice. OLFP attenuated cognitive impairment in SAMP8 mice. Moreover, the results of real-time PCR analysis that followed DNA array analysis in the hippocampus revealed that, compared with SAMP8 mice, the mRNA expression of Wolfram syndrome 1 (Wfs1) was significantly higher in SAMP8 mice administered with OLFP. Wfs1 reportedly helps to protect against endoplasmic reticulum (ER) stress, which is thought to be one of the causes for AD. The expression of Wfs1 was significantly up-regulated in NG108-15 neuronal cells by the treatment with OLFP, and the up-regulation was inhibited by the treatment of the cells with a c-Jun N-terminal kinase-specific inhibitor rather than with an extracellular signal-regulated kinase inhibitor. Moreover, OLFP significantly attenuated the tunicamycin-induced expression of the ER stress marker BiP (immunoglobulin heavy chain-binding protein) in the cells. These results suggest that OLFP has an attenuating effect on early cognitive impairment in SAMP8 mice, and diminishes ER stress in neuronal cells.
authors.affiliation: Department of Molecular Predictive Medicine and Sport Science, School of Medicine, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sakurai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kitadate
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishioka
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujii
authors.forename: Junetsu
authors.initials: J
authors.lastname: Ogasawara
authors.forename: Takako
authors.initials: T
authors.lastname: Kizaki
authors.forename: Shogo
authors.initials: S
authors.lastname: Sato
authors.forename: Tomonori
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Kimio
authors.initials: K
authors.lastname: Akagawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Izawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005638:Fruit / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D032125:Litchi / Q000737:chemistry*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D012333:RNA, Messenger; C514283:oligonol; C114987:wolframin protein; D002392:Catechin