title: Yuzu extract prevents cognitive decline and impaired glucose homeostasis in β-amyloid-infused rats.
abstract: Our preliminary study revealed that dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in β-amyloid-induced rats. Male rats received hippocampal CA1 infusions of β-amyloid (25-35) [plaque forming β-amyloid; Alzheimer disease (AD)] or β-amyloid (35-25) [non-plaque forming β-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal β-amyloid deposition, which was not detected in the C group, and attenuated hippocampal insulin signaling. Yuzu treatment prevented β-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with β-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by β-amyloid infusion.
authors.affiliation: Food Certification Center, Korean Food Research Institutes, Sungnam, South Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Yang
authors.forename: Jin Taek
authors.initials: JT
authors.lastname: Hwang
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Suna
authors.initials: S
authors.lastname: Kang
authors.forename: Na Rang
authors.initials: NR
authors.lastname: Moon
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D002957:Citrus / Q000737:chemistry*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000517:prevention & control; D059305:Diet, High-Fat; D005419:Flavonoids / Q000008:administration & dosage / Q000032:analysis; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects*; D010636:Phenols / Q000008:administration & dosage / Q000032:analysis; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D001786:Blood Glucose; D005419:Flavonoids; D007328:Insulin; D010446:Peptide Fragments; D010636:Phenols; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35)