{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:22:47Z","timestamp":1790036567983,"version":"4.0.1"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010876","name":"Shanghai University of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["No.2013JW02"],"award-info":[{"award-number":["No.2013JW02"]}],"id":[{"id":"10.13039\/501100010876","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Ginkgo biloba<\/jats:italic> extracts (GBE) have been shown to effectively improve cognitive function in patients with Alzheimer\u2019s disease (AD). One potential therapeutic strategy for AD is to prevent loss of adult hippocampal neurons. While recent studies have reported that GBE protects against oxidative stress in neurons, the underlying mechanisms remain unclear. In this study, an AD-like rat model was established via bidirectional injection of amyloid beta 25\u201335 (A\u03b2<jats:sub>25\u201335<\/jats:sub>; 20 \u03bcg) in the hippocampal CA1 region. Learning and memory abilities of experimental rats were AD assessed in response to oral administration of 7.5 g\/L or 15 g\/L <jats:italic>Ginkgo biloba<\/jats:italic> extract 50 (GBE50) solution and the peroxidation phenomenon of hippocampal mitochondria determined via analysis of mitochondrial H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and several related enzymes. Levels of the oxidative stress-related signaling factor cytochrome C (Cyto C), apoptosis-related proteins (Bax, Bcl-2 and caspase-3) and caspase-activated DNase (CAD) were further detected via western blot. 8-Hydroxydeoxyguanosine (8-OHdG), the major product of DNA oxidative stress, was evaluated to analyze DNA status. Our results showed elevated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> levels and monoamine oxidase (MAO) activity, and conversely, a decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus of AD rats. Administration of GBE50 regulated the activities of these three enzymes and induced a decrease in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. GBE50 exerted regulatory effects on abnormally expressed apoptotic proteins in the AD rat hippocampus, enhancing the expression of Bcl-2, inhibiting release of Cyto C from mitochondria, and suppressing the level of caspase-3 (excluding cleaved caspase-3). Furthermore, GBE50 inhibited DNA damage by lowering the generation of 8-OHdG rather than influencing expression of CAD. The collective findings support a protective role of GBE50 in hippocampal neurons of AD-like animals against mitochondrial oxidative stress.<\/jats:p>","DOI":"10.1371\/journal.pone.0307735","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T17:24:06Z","timestamp":1722965046000},"page":"e0307735","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ginkgo biloba extract inhibits hippocampal neuronal injury caused by mitochondrial oxidative stress in a rat model of Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2027-766X","authenticated-orcid":true,"given":"Chenyi","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingmei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"issue":"12","key":"pone.0307735.ref001","first-page":"8342","article-title":"Neuroinflammation in Alzheimer\u2019s disease: chemokines produced by astrocytes and chemokine receptors","volume":"7","author":"C Liu","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"issue":"12","key":"pone.0307735.ref002","doi-asserted-by":"crossref","first-page":"4183","DOI":"10.1523\/JNEUROSCI.21-12-04183.2001","article-title":"Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis","volume":"21","author":"D Pratico","year":"2001","journal-title":"J Neurosci"},{"issue":"1","key":"pone.0307735.ref003","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.expneurol.2009.09.005","article-title":"Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25\u201335)","volume":"221","author":"YG Kaminsky","year":"2010","journal-title":"Exp Neurol"},{"issue":"4\u20135","key":"pone.0307735.ref004","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.neuropharm.2010.04.005","article-title":"Oxidative stress in Alzheimer disease: a possibility for prevention","volume":"59","author":"DJ Bonda","year":"2010","journal-title":"Neuropharmacology"},{"issue":"7","key":"pone.0307735.ref005","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ijdevneu.2004.07.006","article-title":"Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576 mice with Alzheimer-like pathology","volume":"22","author":"J Apelt","year":"2004","journal-title":"Int J Dev Neurosci"},{"issue":"3","key":"pone.0307735.ref006","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1471-4159.2007.05072.x","article-title":"Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein","volume":"104","author":"E Tamagno","year":"2008","journal-title":"J Neurochem"},{"issue":"8","key":"pone.0307735.ref007","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.3390\/molecules24081583","article-title":"Oxidative Stress: A Key Modulator in Neurodegenerative Diseases","volume":"24","author":"A Singh","year":"2019","journal-title":"Molecules"},{"key":"pone.0307735.ref008","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.redox.2017.10.014","article-title":"Oxidative stress and the amyloid beta peptide in Alzheimer\u2019s disease","volume":"14","author":"C Cheignon","year":"2018","journal-title":"Redox Biol"},{"key":"pone.0307735.ref009","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neurobiolaging.2021.07.014","article-title":"Emerging roles of oxidative stress in brain aging and Alzheimer\u2019s disease","volume":"107","author":"A Ionescu-Tucker","year":"2021","journal-title":"Neurobiol Aging"},{"issue":"2","key":"pone.0307735.ref010","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12975-015-0433-7","article-title":"Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1\/Wnt Pathway","volume":"7","author":"J Tulsulkar","year":"2016","journal-title":"Transl Stroke Res"},{"issue":"39","key":"pone.0307735.ref011","doi-asserted-by":"crossref","first-page":"e12421","DOI":"10.1097\/MD.0000000000012421","article-title":"Role of Ginkgo biloba extract as an adjunctive treatment of elderly patients with depression and on the expression of serum S100B","volume":"97","author":"CX Dai","year":"2018","journal-title":"Medicine (Baltimore)"},{"key":"pone.0307735.ref012","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.2147\/NDT.S229296","article-title":"Ginkgo biloba Extract Reduces Hippocampus Inflammatory Responses, Improves Cardiac Functions And Depressive Behaviors In A Heart Failure Mouse Model","volume":"15","author":"L Zhang","year":"2019","journal-title":"Neuropsychiatr Dis Treat"},{"issue":"1","key":"pone.0307735.ref013","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.psc.2012.12.006","article-title":"Ginkgo biloba: indications, mechanisms, and safety","volume":"36","author":"BJ Diamond","year":"2013","journal-title":"Psychiatr Clin North Am"},{"issue":"12","key":"pone.0307735.ref014","doi-asserted-by":"crossref","first-page":"e0225761","DOI":"10.1371\/journal.pone.0225761","article-title":"Ginkgo biloba extract increases neurite outgrowth and activates the Akt\/mTOR pathway","volume":"14","author":"I Lejri","year":"2019","journal-title":"PLoS One"},{"issue":"8","key":"pone.0307735.ref015","doi-asserted-by":"crossref","first-page":"e12359","DOI":"10.1371\/journal.pone.0012359","article-title":"Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure","volume":"5","author":"V Rhein","year":"2010","journal-title":"PLoS One"},{"issue":"8","key":"pone.0307735.ref016","article-title":"Possible use of adaptation to hypoxia in Alzheimer\u2019s disease: a hypothesis","volume":"11","author":"IY Malyshev","year":"2005","journal-title":"Med Sci Monit"},{"issue":"6","key":"pone.0307735.ref017","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1046\/j.1471-4159.2002.01267.x","article-title":"Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer\u2019s disease","volume":"83","author":"NJ Haughey","year":"2002","journal-title":"J Neurochem"},{"issue":"3","key":"pone.0307735.ref018","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2174\/1381612043386437","article-title":"Review about Ginkgo biloba special extract EGb 761 (Ginkgo)","volume":"10","author":"HJ Gertz","year":"2004","journal-title":"Curr Pharm Des"},{"issue":"11","key":"pone.0307735.ref019","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.3390\/molecules16119194","article-title":"Effect of Ginkgo Biloba Extract 50 on Immunity and Antioxidant Enzyme Activities in Ischemia Reperfusion Rats","volume":"16","author":"SP Lu","year":"2011","journal-title":"Molecules"},{"key":"pone.0307735.ref020","doi-asserted-by":"crossref","first-page":"111932","DOI":"10.1016\/j.bbr.2019.111932","article-title":"Exenatide alleviates mitochondrial dysfunction and cognitive impairment in the 5xFAD mouse model of Alzheimer\u2019s disease","volume":"370","author":"J An","year":"2019","journal-title":"Behav Brain Res"},{"key":"pone.0307735.ref021","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.2147\/DDDT.S318515","article-title":"The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation","volume":"15","author":"J Ke","year":"2021","journal-title":"Drug Des Dev Ther"},{"issue":"2","key":"pone.0307735.ref022","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bbr.2007.03.001","article-title":"A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25\u201335)","volume":"180","author":"T Alkam","year":"2007","journal-title":"Behav Brain Res"},{"issue":"1","key":"pone.0307735.ref023","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.neuroscience.2006.11.060","article-title":"A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35","volume":"145","author":"B Klementiev","year":"2007","journal-title":"Neuroscience"},{"issue":"2","key":"pone.0307735.ref024","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1034\/j.1600-079x.2002.1819.x","article-title":"The protective effects of melatonin from oxidative damage induced by amyloid beta-peptide 25\u201335 in middle-aged rats","volume":"32","author":"YX Shen","year":"2002","journal-title":"J Pineal Res"},{"key":"pone.0307735.ref025","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.2147\/JIR.S302934","article-title":"Ginkgo biloba Extract 50 (GBE50) Ameliorates Insulin Resistance, Hepatic Steatosis and Liver Injury in High Fat Diet-Fed Mice","volume":"14","author":"L Li","year":"2021","journal-title":"J Inflamm Res"},{"issue":"23","key":"pone.0307735.ref026","doi-asserted-by":"crossref","first-page":"15305","DOI":"10.3390\/ijms232315305","article-title":"Cross-Regulation between Autophagy and Apoptosis Induced by Vitamin E and Lactobacillus Plantarum through Beclin-1 Network","volume":"23","author":"AM Alhusaini","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"5","key":"pone.0307735.ref027","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/jnc.13851","article-title":"Autophagy activation involved in hypoxic-ischemic brain injury induces cognitive and memory impairment in neonatal rats","volume":"139","author":"Y Xu","year":"2016","journal-title":"J Neurochem"},{"issue":"2","key":"pone.0307735.ref028","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/10590500902885684","article-title":"8-hydroxy-2\u2019 -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis","volume":"27","author":"A Valavanidis","year":"2009","journal-title":"J Environ Sci Health C Environ Carcinog Ecotoxicol Rev"},{"issue":"10","key":"pone.0307735.ref029","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S1474-4422(20)30238-6","article-title":"Potential human transmission of amyloid beta pathology: surveillance and risks","volume":"19","author":"E Lauwers","year":"2020","journal-title":"Lancet Neurol"},{"issue":"2","key":"pone.0307735.ref030","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s11064-019-02940-z","article-title":"Modulatory Effects of Ginkgo biloba Against Amyloid Aggregation Through Induction of Heat Shock Proteins in Aluminium Induced Neurotoxicity","volume":"45","author":"S Verma","year":"2020","journal-title":"Neurochem Res"},{"issue":"3","key":"pone.0307735.ref031","first-page":"1471","article-title":"Ginkgo biloba extract improves cognitive function and increases neurogenesis by reducing Abeta pathology in 5xFAD mice","volume":"13","author":"W Ge","year":"2021","journal-title":"Am J Transl Res"},{"issue":"4","key":"pone.0307735.ref032","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/sj.bjp.0705653","article-title":"Nicotine attenuates beta-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures","volume":"141","author":"Q Liu","year":"2004","journal-title":"Br J Pharmacol"},{"issue":"8","key":"pone.0307735.ref033","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.neuint.2010.03.016","article-title":"H2O2 and PAF mediate Abeta1-42-induced Ca2+ dyshomeostasis that is blocked by EGb761","volume":"56","author":"C Shi","year":"2010","journal-title":"Neurochem Int"},{"issue":"5\u20136","key":"pone.0307735.ref034","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.mito.2004.07.018","article-title":"Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer\u2019s disease","volume":"4","author":"G Aliev","year":"2004","journal-title":"Mitochondrion"},{"issue":"4","key":"pone.0307735.ref035","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10863-005-6631-3","article-title":"Gradual alteration of mitochondrial structure and function by beta-amyloids: importance of membrane viscosity changes, energy deprivation, reactive oxygen species production, and cytochrome c release","volume":"37","author":"AM Aleardi","year":"2005","journal-title":"J Bioenerg Biomembr"},{"issue":"1","key":"pone.0307735.ref036","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.expneurol.2005.07.012","article-title":"CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats","volume":"196","author":"PI Moreira","year":"2005","journal-title":"Exp Neurol"},{"issue":"5","key":"pone.0307735.ref037","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3858\/emm.2012.44.5.035","article-title":"Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation","volume":"44","author":"IH Jung","year":"2012","journal-title":"Exp Mol Med"},{"issue":"9","key":"pone.0307735.ref038","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.jnutbio.2010.08.009","article-title":"EGb 761 (Ginkgo biloba) protects cochlear hair cells against ototoxicity induced by gentamicin via reducing reactive oxygen species and nitric oxide-related apoptosis","volume":"22","author":"TH Yang","year":"2011","journal-title":"J Nutr Biochem"},{"issue":"6","key":"pone.0307735.ref039","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1039\/C5FO00219B","article-title":"Ginkgo biloba extract (Egb761) attenuates zinc-induced tau phosphorylation at Ser262 by regulating GSK3beta activity in rat primary cortical neurons","volume":"6","author":"KJ Kwon","year":"2015","journal-title":"Food Funct"},{"issue":"6","key":"pone.0307735.ref040","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1080\/10715760802159057","article-title":"Effects of amyloid-beta peptides on hydrogen peroxide-metabolizing enzymes in rat brain in vivo","volume":"42","author":"YG Kaminsky","year":"2008","journal-title":"Free Radic Res"},{"issue":"1","key":"pone.0307735.ref041","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3390\/ijms11010107","article-title":"Ginkgo biloba extract in Alzheimer\u2019s disease: from action mechanisms to medical practice","volume":"11","author":"C Shi","year":"2010","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0307735.ref042","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/09537100903395180","article-title":"Ginkgo biloba extract EGb761 protects against mitochondrial dysfunction in platelets and hippocampi in ovariectomized rats","volume":"21","author":"C Shi","year":"2010","journal-title":"Platelets"},{"key":"pone.0307735.ref043","first-page":"7034983","article-title":"Gingko biloba Extract (EGb) Inhibits Oxidative Stress in Neuro 2A Cells Overexpressing APPsw","volume":"2019","author":"L Chen","year":"2019","journal-title":"Biomed Res Int"},{"issue":"5","key":"pone.0307735.ref044","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3109\/09537100903511448","article-title":"Ginkgo biloba extract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice","volume":"21","author":"C Shi","year":"2010","journal-title":"Platelets"},{"issue":"5","key":"pone.0307735.ref045","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.phymed.2011.11.011","article-title":"Ginkgo biloba protects against intermittent hypoxia-induced memory deficits and hippocampal DNA damage in rats","volume":"19","author":"BA Abdel-Wahab","year":"2012","journal-title":"Phytomedicine"},{"issue":"6","key":"pone.0307735.ref046","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1097\/00004647-200106000-00008","article-title":"Amyloid beta peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation","volume":"21","author":"J Xu","year":"2001","journal-title":"J Cereb Blood Flow Metab"},{"issue":"1\u20133","key":"pone.0307735.ref047","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.regpep.2004.05.025","article-title":"Pituitary adenylate cyclase-activating polypeptide inhibits caspase-3 activity but does not protect cerebellar granule neurons against beta-amyloid (25\u201335)-induced apoptosis","volume":"123","author":"D Vaudry","year":"2004","journal-title":"Regul Pept"},{"issue":"12","key":"pone.0307735.ref048","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1002\/hipo.22794","article-title":"NSCs promote hippocampal neurogenesis, metabolic changes and synaptogenesis in APP\/PS1 transgenic mice","volume":"27","author":"W Zhang","year":"2017","journal-title":"Hippocampus"},{"issue":"11","key":"pone.0307735.ref049","doi-asserted-by":"crossref","first-page":"e113126","DOI":"10.1371\/journal.pone.0113126","article-title":"EGb761 provides a protective effect against Abeta1-42 oligomer-induced cell damage and blood-brain barrier disruption in an in vitro bEnd.3 endothelial model","volume":"9","author":"WB Wan","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0307735.ref050","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbi.2009.05.010","article-title":"Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells","volume":"181","author":"C Shi","year":"2009","journal-title":"Chem Biol Interact"},{"issue":"3","key":"pone.0307735.ref051","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cbi.2009.04.008","article-title":"Dosage effects of EGb761 on hydrogen peroxide-induced cell death in SH-SY5Y cells","volume":"180","author":"C Shi","year":"2009","journal-title":"Chem Biol Interact"},{"issue":"6","key":"pone.0307735.ref052","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1471-4159.2010.07160.x","article-title":"Inhibition of cPLA2 activation by Ginkgo biloba extract protects spinal cord neurons from glutamate excitotoxicity and oxidative stress-induced cell death","volume":"116","author":"Z Zhao","year":"2011","journal-title":"J Neurochem"},{"issue":"2","key":"pone.0307735.ref053","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12031-008-9140-0","article-title":"EGb761 protects hydrogen peroxide-induced death of spinal cord neurons through inhibition of intracellular ROS production and modulation of apoptotic regulating genes","volume":"38","author":"X Jiang","year":"2009","journal-title":"J Mol Neurosci"},{"key":"pone.0307735.ref054","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1749-8546-6-8","article-title":"Ginkgo biloba extract (EGb761) inhibits mitochondria-dependent caspase pathway and prevents apoptosis in hypoxia-reoxygenated cardiomyocytes","volume":"6","author":"J Shen","year":"2011","journal-title":"Chin Med"},{"issue":"5","key":"pone.0307735.ref055","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1152\/japplphysiol.91415.2008","article-title":"Ginkgo biloba extract attenuates oxLDL-induced oxidative functional damages in endothelial cells","volume":"106","author":"HC Ou","year":"2009","journal-title":"J Appl Physiol (1985)"},{"issue":"4","key":"pone.0307735.ref056","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuint.2006.12.002","article-title":"RNAi knockdown of caspase-activated DNase inhibits rotenone-induced DNA fragmentation in HeLa cells","volume":"50","author":"T Tsuruta","year":"2007","journal-title":"Neurochem Int"},{"issue":"4","key":"pone.0307735.ref057","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10238-008-0005-1","article-title":"Protective effects of N-acetylcysteine and Ginkgo biloba extract on ischaemia-reperfusion-induced hepatic DNA damage in rats","volume":"8","author":"MS Keles","year":"2008","journal-title":"Clin Exp Med"},{"key":"pone.0307735.ref058","doi-asserted-by":"crossref","first-page":"154796","DOI":"10.1016\/j.phymed.2023.154796","article-title":"Discovery and characterization of the covalent SARS-CoV-2 3CLpro inhibitors from extract via integrating chemoproteomic and biochemical approaches","volume":"114","author":"YN Zhang","year":"2023","journal-title":"Phytomedicine"},{"issue":"5","key":"pone.0307735.ref059","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.3390\/pharmaceutics15051562","article-title":"Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy","volume":"15","author":"T Akanchise","year":"2023","journal-title":"Pharmaceutics"},{"issue":"2","key":"pone.0307735.ref060","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3390\/molecules27020439","article-title":"Study on Synergistic Antioxidant Effect of Typical Functional Components of Hydroethanolic Leaf Extract from Ginkgo Biloba In Vitro","volume":"27","author":"LH Zhang","year":"2022","journal-title":"Molecules"},{"issue":"6","key":"pone.0307735.ref061","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1055\/a-1109-3405","article-title":"Effects of Ginkgo Biloba on Diseases Related to Oxidative Stress","volume":"86","author":"GA de Souza","year":"2020","journal-title":"Planta Med"},{"key":"pone.0307735.ref062","first-page":"481405","article-title":"Protective Effects of Kaempferol against Myocardial Ischemia\/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3\u03b2","volume":"2015","author":"MJ Zhou","year":"2015","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"pone.0307735.ref063","first-page":"2759","article-title":"Recent progress regarding kaempferol for the treatment of various diseases","volume":"18","author":"J Ren","year":"2019","journal-title":"Exp Ther Med"},{"issue":"9","key":"pone.0307735.ref064","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3109\/10715762.2015.1032958","article-title":"Neuroprotective effects of ginkgetin against neuroinjury in Parkinson\u2019s disease model induced by MPTP via chelating iron","volume":"49","author":"YQ Wang","year":"2015","journal-title":"Free Radical Res"},{"issue":"9","key":"pone.0307735.ref065","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1016\/j.bmcl.2013.02.080","article-title":"Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells","volume":"23","author":"OH You","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"pone.0307735.ref066","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/jnc.13436","article-title":"The protective role of isorhamnetin on human brain microvascular endothelial cells from cytotoxicity induced by methylglyoxal and oxygen-glucose deprivation","volume":"136","author":"WL Li","year":"2016","journal-title":"J Neurochem"},{"issue":"2","key":"pone.0307735.ref067","first-page":"140","article-title":"Oral administration of Ginkgolide B alleviates hypoxia-induced neuronal damage in rat hippocampus by inhibiting oxidative stress and apoptosis","volume":"22","author":"L Wang","year":"2019","journal-title":"Iran J Basic Med Sci"},{"issue":"9","key":"pone.0307735.ref068","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1007\/s11064-012-0799-9","article-title":"Neuroprotective effect of natural products against Alzheimer\u2019s disease","volume":"37","author":"MM Essa","year":"2012","journal-title":"Neurochem Res"},{"issue":"4","key":"pone.0307735.ref069","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00253-003-1527-9","article-title":"Studies on molecular mechanisms of Ginkgo biloba extract","volume":"64","author":"JV Smith","year":"2004","journal-title":"Appl Microbiol Biotechnol"},{"issue":"3","key":"pone.0307735.ref070","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12565-015-0297-7","article-title":"Effects of Ginko biloba leaf extract on the neurogenesis of the hippocampal dentate gyrus in the elderly mice","volume":"91","author":"NM Osman","year":"2016","journal-title":"Anat Sci Int"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307735","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T17:24:45Z","timestamp":1722965085000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307735"}},"subtitle":[],"editor":[{"given":"Tosin Abiola","family":"Olasehinde","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":70,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307735","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,6]]}}}