{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:37:51Z","timestamp":1793824671768,"version":"4.6.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.phymed.2024.156327","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T03:40:48Z","timestamp":1734234048000},"page":"156327","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Ginkgo biloba extract EGb 761\u00ae ameliorates cognitive impairment and alleviates TNF\u03b1 response in 5xFAD Alzheimer\u2018s disease model mice"],"prefix":"10.1016","volume":"136","author":[{"given":"Vu Thu Thuy","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Subirana","family":"Slotos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5183-4476","authenticated-orcid":false,"given":"Malena Dos Santos","family":"Guilherme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-3225","authenticated-orcid":false,"given":"Tinh Thi","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Weisenburger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3279-1092","authenticated-orcid":false,"given":"Martin D.","family":"Lehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-8287","authenticated-orcid":false,"given":"Kristina","family":"Endres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phymed.2024.156327_bib0001","unstructured":"Agency, E.M. (2015). \"European union herbal monograph on ginkgo biloba L., folium.\" EMA\/HMPC\/321097\/2012."},{"issue":"4558","key":"10.1016\/j.phymed.2024.156327_bib0002","first-page":"408","article-title":"The cholinergic hypothesis of geriatric memory dysfunction","volume":"217","author":"Bartus","year":"1982","journal-title":"Science (1979)"},{"issue":"2","key":"10.1016\/j.phymed.2024.156327_bib0003","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.pharmthera.2013.12.009","article-title":"Genetic mouse models of brain ageing and Alzheimer's disease","volume":"142","author":"Bilkei-Gorzo","year":"2014","journal-title":"Pharmacol. Ther."},{"issue":"9","key":"10.1016\/j.phymed.2024.156327_bib0004","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20202717","article-title":"Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?","volume":"218","author":"Chen","year":"2021","journal-title":"J. Exp. Med."},{"issue":"1","key":"10.1016\/j.phymed.2024.156327_bib0005","doi-asserted-by":"crossref","first-page":"e12346","DOI":"10.1002\/dad2.12346","article-title":"Higher baseline levels of CSF inflammation increase risk of incident mild cognitive impairment and Alzheimer's disease dementia","volume":"14","author":"Contreras","year":"2022","journal-title":"Alzheimers. Dement. (Amst)"},{"issue":"1","key":"10.1016\/j.phymed.2024.156327_bib0006","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1389450003349380","article-title":"Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications","volume":"1","author":"DeFeudis","year":"2000","journal-title":"Curr. Drug Targets."},{"key":"10.1016\/j.phymed.2024.156327_bib0007","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fnagi.2019.00182","article-title":"The synthetic retinoid acitretin increases IL-6 in the central nervous system of alzheimer disease model mice and human patients","volume":"11","author":"Dos Santos Guilherme","year":"2019","journal-title":"Front. Aging Neurosci."},{"issue":"3","key":"10.1016\/j.phymed.2024.156327_bib0008","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1152\/physrev.00015.2020","article-title":"The complexity of Alzheimer's disease: an evolving puzzle","volume":"101","author":"Ferrari","year":"2021","journal-title":"Physiol. Rev."},{"issue":"9","key":"10.1016\/j.phymed.2024.156327_bib0009","doi-asserted-by":"crossref","first-page":"e75091","DOI":"10.1371\/journal.pone.0075091","article-title":"Increased neurofilament light chain blood levels in neurodegenerative neurological diseases","volume":"8","author":"Gaiottino","year":"2013","journal-title":"PLoS One"},{"issue":"6665","key":"10.1016\/j.phymed.2024.156327_bib0010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/34800","article-title":"Alzheimer's disease. A technical KO of amyloid-beta peptide","volume":"391","author":"Haass","year":"1998","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.phymed.2024.156327_bib0011","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/j.neuropharm.2009.11.002","article-title":"Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice","volume":"58","author":"Hou","year":"2010","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phymed.2024.156327_bib0012","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jpba.2014.07.030","article-title":"Effects of food and gender on the pharmacokinetics of ginkgolides A, B, C and bilobalide in rats after oral dosing with ginkgo terpene lactones extract","volume":"100","author":"Huang","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"4","key":"10.1016\/j.phymed.2024.156327_bib0013","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s12276-022-00754-8","article-title":"\u03b3-Secretase in Alzheimer's disease","volume":"54","author":"Hur","year":"2022","journal-title":"Exp. Mol. Med."},{"issue":"3","key":"10.1016\/j.phymed.2024.156327_bib0014","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1523\/JNEUROSCI.2110-16.2016","article-title":"Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer's disease","volume":"37","author":"Jay","year":"2017","journal-title":"J. Neurosci."},{"key":"10.1016\/j.phymed.2024.156327_bib0015","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1007746","article-title":"Ginkgo biloba leaf extract EGb 761(\u00ae) as a paragon of the product by process concept","volume":"13","author":"Kuli\u0107","year":"2022","journal-title":"Front. Pharmacol."},{"issue":"5","key":"10.1016\/j.phymed.2024.156327_bib0016","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1055\/a-1379-4553","article-title":"A detailed view on the proanthocyanidins in ginkgo extract EGb 761","volume":"88","author":"Kuli\u0107","year":"2022","journal-title":"Planta Med."},{"key":"10.1016\/j.phymed.2024.156327_bib0017","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bbi.2015.01.011","article-title":"Long-term treatment with Ginkgo biloba extract EGb 761 improves symptoms and pathology in a transgenic mouse model of Alzheimer's disease","volume":"46","author":"Liu","year":"2015","journal-title":"Brain Behav. Immun."},{"issue":"20","key":"10.1016\/j.phymed.2024.156327_bib0018","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.1563-23.2024","article-title":"Imbalance in glucose metabolism regulates the transition of microglia from homeostasis to disease-associated microglia stage 1","volume":"44","author":"Liu","year":"2024","journal-title":"J. Neurosci."},{"key":"10.1016\/j.phymed.2024.156327_bib0019","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3389\/fnins.2020.00579","article-title":"Neurofilament-light chain as biomarker of neurodegenerative and rare diseases with high translational value","volume":"14","author":"Loeffler","year":"2020","journal-title":"Front. Neurosci."},{"issue":"2","key":"10.1016\/j.phymed.2024.156327_bib0020","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"issue":"4","key":"10.1016\/j.phymed.2024.156327_bib0021","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00401-020-02200-3","article-title":"APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer's disease","volume":"140","author":"Nguyen","year":"2020","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.phymed.2024.156327_bib0022","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.775034","article-title":"The use of ginkgo biloba l. as a neuroprotective agent in the Alzheimer's disease","volume":"12","author":"Nowak","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"40","key":"10.1016\/j.phymed.2024.156327_bib0023","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J. Neurosci."},{"key":"10.1016\/j.phymed.2024.156327_bib0024","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2022.108953","article-title":"Minocycline suppresses disease-associated microglia (DAM) in a model of photoreceptor cell degeneration","volume":"217","author":"Ozaki","year":"2022","journal-title":"Exp. Eye Res."},{"issue":"5","key":"10.1016\/j.phymed.2024.156327_bib0025","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1755-5949.2010.00164.x","article-title":"REVIEW: \u03b3-Secretase inhibitors for the treatment of Alzheimer's disease: the current state","volume":"16","author":"Panza","year":"2010","journal-title":"CNS Neurosci Ther"},{"issue":"4","key":"10.1016\/j.phymed.2024.156327_bib0026","doi-asserted-by":"crossref","first-page":"437","DOI":"10.31887\/DCNS.2016.18.4\/cepperson","article-title":"Considering sex and gender in Alzheimer disease and other dementias","volume":"18","author":"Podcasy","year":"2016","journal-title":"Dialogues. Clin. Neurosci."},{"issue":"2","key":"10.1016\/j.phymed.2024.156327_bib0027","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nn.4475","article-title":"The role of peripheral immune cells in the CNS in steady state and disease","volume":"20","author":"Prinz","year":"2017","journal-title":"Nat. Neurosci."},{"issue":"23","key":"10.1016\/j.phymed.2024.156327_bib0028","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232314506","article-title":"Behavioral phenotyping of Bbs6 and Bbs8 knockout mice reveals major alterations in communication and anxiety","volume":"23","author":"R\u00f6dig","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"24","key":"10.1016\/j.phymed.2024.156327_bib0029","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abo1286","article-title":"BACE-1 inhibition facilitates the transition from homeostatic microglia to DAM-1","volume":"8","author":"Singh","year":"2022","journal-title":"Sci. Adv."},{"issue":"13","key":"10.1016\/j.phymed.2024.156327_bib0030","doi-asserted-by":"crossref","DOI":"10.3390\/cells11132021","article-title":"Single-Cell RNA-Sequencing: astrocyte and Microglial Heterogeneity in Health and Disease","volume":"11","author":"Spurgat","year":"2022","journal-title":"Cells"},{"issue":"1","key":"10.1016\/j.phymed.2024.156327_bib0031","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/S0014-4886(03)00399-6","article-title":"Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment","volume":"184","author":"Stackman","year":"2003","journal-title":"Exp. Neurol."},{"issue":"9","key":"10.1016\/j.phymed.2024.156327_bib0032","doi-asserted-by":"crossref","first-page":"11883","DOI":"10.1096\/fj.201903128RR","article-title":"Alzheimer's disease in the gut-Major changes in the gut of 5xFAD model mice with ApoA1 as potential key player","volume":"34","author":"Stoye","year":"2020","journal-title":"FASEB J."},{"issue":"5","key":"10.1016\/j.phymed.2024.156327_bib0033","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s12264-016-0055-4","article-title":"Inflammatory Cytokines and Alzheimer's Disease: a Review from the Perspective of Genetic Polymorphisms","volume":"32","author":"Su","year":"2016","journal-title":"Neurosci. Bull."},{"issue":"4","key":"10.1016\/j.phymed.2024.156327_bib0034","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.drudis.2022.01.016","article-title":"Challenges and hopes for Alzheimer's disease","volume":"27","author":"Tatulian","year":"2022","journal-title":"Drug. Discov. Today"},{"key":"10.1016\/j.phymed.2024.156327_bib0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2022.114418","article-title":"Targeting gut microbiota to alleviate neuroinflammation in Alzheimer's disease","volume":"188","author":"Thu Thuy Nguyen","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"12","key":"10.1016\/j.phymed.2024.156327_bib0036","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms9122548","article-title":"Impact of the age of cecal material transfer donors on alzheimer's disease pathology in 5xFAD Mice","volume":"9","author":"Valeri","year":"2021","journal-title":"Microorganisms"},{"key":"10.1016\/j.phymed.2024.156327_bib0037","doi-asserted-by":"crossref","first-page":"990","DOI":"10.3389\/fnins.2019.00990","article-title":"Myeloperoxidase deficiency inhibits cognitive decline in the 5XFAD mouse model of Alzheimer's disease","volume":"13","author":"Volkman","year":"2019","journal-title":"Front. Neurosci."},{"issue":"8","key":"10.1016\/j.phymed.2024.156327_bib0038","doi-asserted-by":"crossref","first-page":"622","DOI":"10.3109\/15622975.2015.1066513","article-title":"Efficacy of Ginkgo biloba extract EGb 761(\u00ae) in dementia with behavioural and psychological symptoms: a systematic review","volume":"17","author":"von Gunten","year":"2016","journal-title":"World J. Biol. Psychiatry"},{"key":"10.1016\/j.phymed.2024.156327_bib0039","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.exger.2016.05.007","article-title":"EGb761 improves cognitive function and regulates inflammatory responses in the APP\/PS1 mouse","volume":"81","author":"Wan","year":"2016","journal-title":"Exp. Gerontol."},{"issue":"3","key":"10.1016\/j.phymed.2024.156327_bib0040","doi-asserted-by":"crossref","DOI":"10.3390\/cells11030479","article-title":"Can we use ginkgo biloba extract to treat alzheimer's disease? lessons from preclinical and clinical studies","volume":"11","author":"Xie","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.phymed.2024.156327_bib0041","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113711","article-title":"Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 7C1) via further improvement in pro-cholinergic and antioxidative activities","volume":"269","author":"Zhao","year":"2021","journal-title":"J Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.phymed.2024.156327_bib0042","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41591-019-0695-9","article-title":"Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer's disease","volume":"26","author":"Zhou","year":"2020","journal-title":"Nat. Med."}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324009826?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711324009826?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:11:27Z","timestamp":1740355887000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711324009826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":42,"alternative-id":["S0944711324009826"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2024.156327","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ginkgo biloba extract EGb 761\u00ae ameliorates cognitive impairment and alleviates TNF\u03b1 response in 5xFAD Alzheimer\u2018s disease model mice","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2024.156327","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier GmbH.","name":"copyright","label":"Copyright"}],"article-number":"156327"}}