{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:10:36Z","timestamp":1790003436901,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Pecan (Carya illinoinensis) is an edible nut rich in phytochemicals with potential health-promoting properties; however, the bioactive constituents responsible for its neuroprotective effects remain insufficiently characterized. This study aimed to identify bioactive constituents from pecan through bioactivity-guided fractionation and to evaluate the protective effects of pecan extract and the identified compound against oxidative stress and amyloid beta (A\u03b2)1\u201342-induced cognitive impairment. Pecan ethanolic extract exhibited antioxidant and cytoprotective activities in PC12 cells exposed to hydrogen peroxide-induced oxidative stress. Sequential liquid\u2013liquid fractionation, silica gel open-column chromatography, and preparative thin-layer chromatography, coupled with repeated bioactivity screening, progressively tracked the active fractions and led to the identification of ethyl gallate as a bioactive constituent of pecan extract by high-performance liquid chromatography and gas chromatography\u2013mass spectrometry. The biological relevance of these findings was further evaluated in A\u03b21\u201342-injected male mice. Dietary administration of pecan extract significantly improved spontaneous alternation performance in the Y-maze test, whereas ethyl gallate improved Y-maze performance and memory retention in the passive avoidance test, without apparent systemic toxicity under the experimental conditions. Although brain malondialdehyde levels showed a numerical decrease following ethyl gallate administration, the differences were not statistically significant. Collectively, these findings demonstrate the bioactivity-guided linkage of ethyl gallate to an active pecan fraction and provide preclinical evidence supporting further investigation of pecan-derived bioactives as food-derived functional ingredients relevant to cognitive health.<\/jats:p>","DOI":"10.3390\/foods15183316","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:12:09Z","timestamp":1789999929000},"page":"3316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactivity-Guided Identification of Ethyl Gallate from Pecan (Carya illinoinensis) and Its Protective Effects Against Oxidative Stress and Amyloid-\u03b2-Induced Cognitive Impairment"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9110-9656","authenticated-orcid":false,"given":"Chan Kyu","family":"Park","sequence":"first","affiliation":[{"name":"Department of Food and Biotechnology, Korea University, Sejong 30019, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Dong-Hoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Food and Biotechnology, Korea University, Sejong 30019, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","first-page":"135","article-title":"Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer\u2019s Disease","volume":"2","author":"Morris","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/jnc.15538","article-title":"Biological and methodological complexities of beta-amyloid peptide: Implications for Alzheimer\u2019s disease research","volume":"160","author":"Matuszyk","year":"2022","journal-title":"J. Neurochem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Marttinen, M., Takalo, M., Natunen, T., Wittrahm, R., Gabbouj, S., Kemppainen, S., Leinonen, V., Tanila, H., Haapasalo, A., and Hiltunen, M. (2018). Molecular Mechanisms of Synaptotoxicity and Neuroinflammation in Alzheimer\u2019s Disease. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00963"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000440844","article-title":"Tau as the Converging Protein between Chronic Stress and Alzheimer\u2019s Disease Synaptic Pathology","volume":"16","author":"Sotiropoulos","year":"2016","journal-title":"Neurodegener. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stellick (Bedrejo), C.A., Greenshaw, A., Paulden, M., Yap, S., Marshall, R.T., Kung, J.Y., and Spackman, E. (2024). Do beta-amyloid-targeted interventions improve cognition, physical functioning, and overt behaviour of Alzheimer\u2019s Disease (AD) patients: Protocol for meta-analysis of Phase 3 clinical trials both completed and terminated. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0307761"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1074\/jbc.M404751200","article-title":"Curcumin Inhibits Formation of Amyloid \u03b2 Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo","volume":"280","author":"Yang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/acn3.431","article-title":"Extra-virgin olive oil ameliorates cognition and neuropathology of the 3xTg mice: Role of autophagy","volume":"4","author":"Lauretti","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.nutres.2006.06.022","article-title":"A pecan-enriched diet increases \u03b3-tocopherol\/cholesterol and decreases thiobarbituric acid reactive substances in plasma of adults","volume":"26","author":"Haddad","year":"2006","journal-title":"Nutr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3945\/jn.110.121269","article-title":"Pecans Acutely Increase Plasma Postprandial Antioxidant Capacity and Catechins and Decrease LDL Oxidation in Humans","volume":"141","author":"Hudthagosol","year":"2011","journal-title":"J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.maturitas.2015.10.014","article-title":"Nut consumption and age-related disease","volume":"84","author":"Grosso","year":"2016","journal-title":"Maturitas"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Delgadillo-Puga, C., Torre-Villalvazo, I., Noriega, L., Rodr\u00edguez-L\u00f3pez, L., Alem\u00e1n, G., Torre-Anaya, E., Cari\u00f1o-Cervantes, Y.Y., Palacios-Gonzalez, B., Furuzawa-Carballeda, J., and Tovar, A.R. (2023). Pecans and Its Polyphenols Prevent Obesity, Hepatic Steatosis and Diabetes by Reducing Dysbiosis, Inflammation, and Increasing Energy Expenditure in Mice Fed a High-Fat Diet. Nutrients, 15.","DOI":"10.3390\/nu15112591"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Park, C.K., Choi, S.J., Kim, C.R., Shin, H.R., Shin, E.-C., Kim, Y.J., Cho, T.J., Shin, D.H., and Kim, J.K. (2025). Ethanolic Extract of Rosa rugosa Roots and Its Bioactive Compound, Oleamide, Prevented Amyloid \u03b2-Induced Oxidative Stress and Improved Behavioral Tests in Mice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094214"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1271\/bbb.90585","article-title":"Protective Effects of Kaempferol (3,4\u2032,5,7-tetrahydroxyflavone) against Amyloid Beta Peptide (A\u03b2)-Induced Neurotoxicity in ICR Mice","volume":"74","author":"KIM","year":"2010","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1089\/jmf.2012.0280","article-title":"Effects of brussels sprouts and their phytochemical components on oxidative stress-induced neuronal damages in PC12 cells and ICR mice","volume":"16","author":"Kim","year":"2013","journal-title":"J. Med. Food"},{"key":"ref_15","first-page":"e53308","article-title":"Intracerebroventricular injection of amyloid-\u03b2 peptides in normal mice to acutely induce Alzheimer-like cognitive deficits","volume":"109","author":"Kim","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmed.2007.12.002","article-title":"Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer\u2019s disease","volume":"14","author":"Reddy","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1080\/1028415X.2025.2461018","article-title":"Cognitive function in response to a pecan-enriched meal: A randomized, double-blind, cross-over study in healthy adults","volume":"28","author":"Guadagni","year":"2025","journal-title":"Nutr. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3233\/NHA-220181","article-title":"Effects of a 4-week pecan-enriched diet on cognitive function in healthy older adults","volume":"7","author":"Cogan","year":"2022","journal-title":"Nutr. Healthy Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"150925","DOI":"10.1016\/j.bbrc.2024.150925","article-title":"Ethyl gallate ameliorates diabetes-induced Alzheimer\u2019s disease-like phenotype in rats via activation of \u03b17 nicotinic receptors and mitigation of oxidative stress","volume":"737","author":"Nagori","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.foodchem.2014.07.092","article-title":"The pecan nut (Carya illinoinensis) and its oil and polyphenolic fractions differentially modulate lipid metabolism and the antioxidant enzyme activities in rats fed high-fat diets","volume":"168","year":"2015","journal-title":"Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1046\/j.1432-1327.1999.00957.x","article-title":"Interactions of Alzheimer amyloid-\u03b2 peptides with glycosaminoglycans","volume":"266","author":"McLaurin","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11011-019-0382-z","article-title":"Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells","volume":"34","author":"Chen","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1556\/1326.2017.00147","article-title":"Research on the neuro-protective compounds in Terminalia chebula retz extracts in-vivo by UPLC\u2013QTOF-MS","volume":"30","author":"Zhang","year":"2018","journal-title":"Acta Chromatogr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Lee, C.-H., and Hung, S.-Y. (2022). Physiologic Functions and Therapeutic Applications of \u03b17 Nicotinic Acetylcholine Receptor in Brain Disorders. 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