{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:33:56Z","timestamp":1792010036698,"version":"4.4.0"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Ministry of Science and ICT","award":["NRF-2016M3C1B5907049"],"award-info":[{"award-number":["NRF-2016M3C1B5907049"]}]},{"name":"Ministry of Science and ICT","award":["NRF-2015R1D1A3A01019577"],"award-info":[{"award-number":["NRF-2015R1D1A3A01019577"]}]}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.fr","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Nutrition Research"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1016\/j.nutres.2018.09.010","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T21:58:04Z","timestamp":1538431084000},"page":"116-131","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":63,"special_numbering":"C","title":["The combination of luteolin and l-theanine improved Alzheimer disease\u2013like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-\u03b2\u2013infused rats"],"prefix":"10.1016","volume":"60","author":[{"given":"Sunmin","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Sol","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nutres.2018.09.010_bb0005","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuropharm.2015.01.027","article-title":"The flavonoid quercetin ameliorates Alzheimer's disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer's disease model mice","volume":"93","author":"Sabogal-Guaqueta","year":"2015","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.nutres.2018.09.010_bb0010","first-page":"1299","article-title":"Meta-analysis of modifiable risk factors for Alzheimer's disease","volume":"86","author":"Xu","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.1016\/j.nutres.2018.09.010_bb0015","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3945\/jn.112.173401","article-title":"Yuzu extract prevents cognitive decline and impaired glucose homeostasis in beta-amyloid-infused rats","volume":"143","author":"Yang","year":"2013","journal-title":"J Nutr"},{"key":"10.1016\/j.nutres.2018.09.010_bb0020","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3233\/JAD-2008-14302","article-title":"Gossypium herbaceam extracts inhibited NF-kappaB activation to attenuate spatial memory impairment and hippocampal neurodegeneration induced by amyloid-beta in rats","volume":"14","author":"Ji","year":"2008","journal-title":"J Alzheimers Dis"},{"key":"10.1016\/j.nutres.2018.09.010_bb0025","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.neuropharm.2017.11.027","article-title":"Impaired peripheral glucose homeostasis and Alzheimer's disease","volume":"136","author":"Wijesekara","year":"2018","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.nutres.2018.09.010_bb0030","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.metabol.2013.08.007","article-title":"beta-Amyloid\u2013induced cognitive dysfunction impairs glucose homeostasis by increasing insulin resistance and decreasing beta-cell mass in non-diabetic and diabetic rats","volume":"62","author":"Park","year":"2013","journal-title":"Metabolism"},{"key":"10.1016\/j.nutres.2018.09.010_bb0035","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/brain\/awv326","article-title":"Is amyloid-beta harmful to the brain? Insights from human imaging studies","volume":"139","author":"Jagust","year":"2016","journal-title":"Brain"},{"key":"10.1016\/j.nutres.2018.09.010_bb0040","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13195-017-0241-2","article-title":"Role of neuroinflammation in neurodegeneration: new insights","volume":"9","author":"McManus","year":"2017","journal-title":"Alzheimers Res Ther"},{"key":"10.1016\/j.nutres.2018.09.010_bb0045","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer's disease: current evidence and future directions","volume":"12","author":"Calsolaro","year":"2016","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.nutres.2018.09.010_bb0050","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnins.2015.00204","article-title":"Aberrant insulin signaling in Alzheimer's disease: current knowledge","volume":"9","author":"Bedse","year":"2015","journal-title":"Front Neurosci"},{"key":"10.1016\/j.nutres.2018.09.010_bb0055","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.npep.2017.04.001","article-title":"Effect of amyloid-beta (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein","volume":"63","author":"Lozano","year":"2017","journal-title":"Neuropeptides"},{"key":"10.1016\/j.nutres.2018.09.010_bb0060","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.brainresbull.2011.03.024","article-title":"Neuroprotective effects of puerarin against beta-amyloid\u2013induced neurotoxicity in PC12 cells via a PI3K-dependent signaling pathway","volume":"85","author":"Xing","year":"2011","journal-title":"Brain Res Bull"},{"key":"10.1016\/j.nutres.2018.09.010_bb0065","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1055\/s-0034-1382864","article-title":"Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in adipocytes with regulation of AMP-activated kinase and\/or sirtuin 1 activity","volume":"80","author":"Xiao","year":"2014","journal-title":"Planta Med"},{"key":"10.1016\/j.nutres.2018.09.010_bb0070","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1002\/mnfr.201300830","article-title":"Low-dose diet supplement of a natural flavonoid, luteolin, ameliorates diet-induced obesity and insulin resistance in mice","volume":"58","author":"Xu","year":"2014","journal-title":"Mol Nutr Food Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0075","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/mnfr.200800495","article-title":"Naturally occurring flavonoids attenuate high glucose-induced expression of proinflammatory cytokines in human monocytic THP-1 cells","volume":"53","author":"Wu","year":"2009","journal-title":"Mol Nutr Food Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0080","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3390\/ijms15010895","article-title":"Luteolin reduces Alzheimer's disease pathologies induced by traumatic brain injury","volume":"15","author":"Sawmiller","year":"2014","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.nutres.2018.09.010_bb0085","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10571-017-0521-1","article-title":"Brain under stress and Alzheimer's disease","volume":"38","author":"Mravec","year":"2018","journal-title":"Cell Mol Neurobiol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0090","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.febslet.2014.11.026","article-title":"The green tea polyphenol (\u2212)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios","volume":"589","author":"Wobst","year":"2015","journal-title":"FEBS Lett"},{"key":"10.1016\/j.nutres.2018.09.010_bb0095","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.freeradbiomed.2009.09.008","article-title":"l-theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK\/p38 kinase and NF-kappaB pathways","volume":"47","author":"Kim","year":"2009","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.nutres.2018.09.010_bb0100","doi-asserted-by":"crossref","first-page":"475","DOI":"10.2174\/1570159X13666141204220539","article-title":"Can tea consumption be a safe and effective therapy against diabetes mellitus\u2013induced neurodegeneration?","volume":"12","author":"Nunes","year":"2014","journal-title":"Curr Neuropharmacol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0105","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2017.08.031","article-title":"Emerging role of amyloid beta in stress response: implication for depression and diabetes","volume":"817","author":"Morgese","year":"2017","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0110","series-title":"Guidance for industry on estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers","author":"Food and Drug Administration","year":"2005"},{"key":"10.1016\/j.nutres.2018.09.010_bb0115","doi-asserted-by":"crossref","first-page":"7657","DOI":"10.3892\/mmr.2015.4348","article-title":"Synergistic topical application of salt-processed Phellodendron amurense and Sanguisorba officinalis Linne alleviates atopic dermatitis symptoms by reducing levels of immunoglobulin E and pro-inflammatory cytokines in NC\/Nga mice","volume":"12","author":"Park","year":"2015","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.nutres.2018.09.010_bb0120","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1167\/iovs.14-14486","article-title":"Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells","volume":"55","author":"Tripathi","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.nutres.2018.09.010_bb0125","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.nutres.2018.09.010_bb0130","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1002\/mnfr.201400470","article-title":"Green tea changes serum and liver metabolomic profiles in mice with high-fat diet\u2013induced obesity","volume":"59","author":"Lee","year":"2015","journal-title":"Mol Nutr Food Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0135","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.toxrep.2016.06.005","article-title":"Brain regions and monoaminergic neurotransmitters that are involved in mouse ambulatory activity promoted by bupropion","volume":"3","author":"Umezu","year":"2016","journal-title":"Toxicol Rep"},{"key":"10.1016\/j.nutres.2018.09.010_bb0140","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.jnutbio.2012.08.006","article-title":"Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats","volume":"24","author":"Kwon","year":"2013","journal-title":"J Nutr Biochem"},{"key":"10.1016\/j.nutres.2018.09.010_bb0145","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1172\/JCI11559","article-title":"Prevention of fat-induced insulin resistance by salicylate","volume":"108","author":"Kim","year":"2001","journal-title":"J Clin Invest"},{"key":"10.1016\/j.nutres.2018.09.010_bb0150","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.2337\/diabetes.51.6.1825","article-title":"The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats","volume":"51","author":"Dobbins","year":"2002","journal-title":"Diabetes"},{"key":"10.1016\/j.nutres.2018.09.010_bb0155","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbr.2014.02.040","article-title":"Luteolin protects against high fat diet-induced cognitive deficits in obesity mice","volume":"267","author":"Liu","year":"2014","journal-title":"Behav Brain Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0160","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2015.09.002","article-title":"Luteolin as an anti-inflammatory and neuroprotective agent: a brief review","volume":"119","author":"Nabavi","year":"2015","journal-title":"Brain Res Bull"},{"key":"10.1016\/j.nutres.2018.09.010_bb0165","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0155400","article-title":"ABCG1 and ABCG4 suppress gamma-secretase activity and amyloid beta production","volume":"11","author":"Sano","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.nutres.2018.09.010_bb0170","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/sj.bjp.0706927","article-title":"The anti-amnesic and neuroprotective effects of donepezil against amyloid beta25-35 peptide\u2013induced toxicity in mice involve an interaction with the sigma1 receptor","volume":"149","author":"Meunier","year":"2006","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0175","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0006-8993(95)01032-7","article-title":"Amnesia induced in mice by centrally administered beta-amyloid peptides involves cholinergic dysfunction","volume":"706","author":"Maurice","year":"1996","journal-title":"Brain Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0180","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1007\/s11064-012-0822-1","article-title":"Protective effect of luteolin in experimental ischemic stroke: upregulated SOD1, CAT, Bcl-2 and claudin-5, down-regulated MDA and Bax expression","volume":"37","author":"Qiao","year":"2012","journal-title":"Neurochem Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0185","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2012.02.003","article-title":"Luteolin downregulates TLR4, TLR5, NF-kappaB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia","volume":"1448","author":"Qiao","year":"2012","journal-title":"Brain Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0190","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.3390\/molecules16032084","article-title":"Luteolin isolated from the medicinal plant Elsholtzia rugulosa (Labiatae) prevents copper-mediated toxicity in beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells","volume":"16","author":"Liu","year":"2011","journal-title":"Molecules"},{"key":"10.1016\/j.nutres.2018.09.010_bb0195","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3988\/jcn.2011.7.1.10","article-title":"A common pathogenic mechanism linking type-2 diabetes and Alzheimer's disease: evidence from animal models","volume":"7","author":"Park","year":"2011","journal-title":"J Clin Neurol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0200","doi-asserted-by":"crossref","first-page":"190","DOI":"10.15252\/emmm.201404183","article-title":"Alzheimer-associated Abeta oligomers impact the central nervous system to induce peripheral metabolic deregulation","volume":"7","author":"Clarke","year":"2015","journal-title":"EMBO Mol Med"},{"key":"10.1016\/j.nutres.2018.09.010_bb0205","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nrneurol.2015.147","article-title":"Alzheimer disease: insulin resistance could be linked to risk of AD via reduced glucose uptake","volume":"11","author":"Malkki","year":"2015","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.nutres.2018.09.010_bb0210","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.neuro.2008.03.004","article-title":"Protective effect of the green tea component, l-theanine on environmental toxins-induced neuronal cell death","volume":"29","author":"Cho","year":"2008","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.nutres.2018.09.010_bb0215","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/ptr.4868","article-title":"l-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion","volume":"27","author":"Zukhurova","year":"2013","journal-title":"Phytother Res"},{"key":"10.1016\/j.nutres.2018.09.010_bb0220","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1750-1326-4-54","article-title":"Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment","volume":"4","author":"de la Monte","year":"2009","journal-title":"Mol Neurodegener"},{"key":"10.1016\/j.nutres.2018.09.010_bb0225","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1096\/fj.201700346R","article-title":"The amyloid precursor protein modulates alpha2A-adrenergic receptor endocytosis and signaling through disrupting arrestin 3 recruitment","volume":"31","author":"Zhang","year":"2017","journal-title":"FASEB J"},{"key":"10.1016\/j.nutres.2018.09.010_bb0230","series-title":"Rang & Dale's pharmacology","author":"Flower","year":"2007"},{"key":"10.1016\/j.nutres.2018.09.010_bb0235","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neurobiolaging.2012.05.019","article-title":"A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease","volume":"34","author":"Robertson","year":"2013","journal-title":"Neurobiol Aging"}],"container-title":["Nutrition Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0271531718303683?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0271531718303683?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T03:10:13Z","timestamp":1544411413000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0271531718303683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12]]},"references-count":47,"alternative-id":["S0271531718303683"],"URL":"https:\/\/doi.org\/10.1016\/j.nutres.2018.09.010","relation":{},"ISSN":["0271-5317"],"issn-type":[{"value":"0271-5317","type":"print"}],"subject":[],"published":{"date-parts":[[2018,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The combination of luteolin and l-theanine improved Alzheimer disease\u2013like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-\u03b2\u2013infused rats","name":"articletitle","label":"Article Title"},{"value":"Nutrition Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nutres.2018.09.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}