{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:05:18Z","timestamp":1791021918900,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bioactive compounds from edible plants represent a promising multi\u2010target approach for mitigating Alzheimer's disease (AD), in which neuroinflammation is a key pathological driver. Building on previous evidence that\n                    <jats:italic>Citri Reticulatae<\/jats:italic>\n                    Semen extract (CRSE) exerts neuroprotective effects, this study investigated its impact on AD related neuroinflammation and the underlying mechanisms. The major constituents of CRSE were profiled by HPLC\u2010MS. CRSE efficacy was evaluated in A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    stimulated BV\u20102 microglia, 3\u00d7Tg\u2010AD mice, and Tg (apoeb: lynEGFP) zebrafish larvae. We found that CRSE significantly suppressed A\u03b2\u2010induced microglial activation, NLRP3 inflammasome signaling, and pro\u2010inflammatory cytokine release in BV\u20102 cells. In 3\u00d7Tg\u2010AD mice, CRSE supplementation improved spatial learning and memory, reduced hippocampal glial reactivity and neuronal loss, and attenuated tau pathology and NLRP3\/ASC\/Caspase\u20101 activation. It also reduced microglial activation in zebrafish. Integrated transcriptomics and network pharmacology analyses converged on the PI3K\/Akt\/FoxO1 axis. Subsequent validation demonstrated that CRSE restored A\u03b2\u2010impaired phosphorylation of PI3K, Akt, and FoxO1, and its anti\u2010inflammatory effects were attenuated by the PI3K inhibitor. Collectively, these findings demonstrate that the fruit\u2010derived CRSE ameliorates AD\u2010related pathology by modulating the PI3K\/Akt\/FoxO1 pathway and suppressing NLRP3 inflammasome activation. This study provides a mechanistic basis for considering CRSE as a botanical candidate for dietary interventions aimed at neuroprotection in AD.\n                  <\/jats:p>","DOI":"10.1002\/mnfr.70452","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T10:56:06Z","timestamp":1775732166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fruit\u2010Derived\n                    <i>Citri Reticulatae<\/i>\n                    Semen Extract Attenuates Alzheimer's Disease Neuroinflammation and Cognitive Impairment via Modulation of the PI3K\/Akt\/FoxO1 Pathway"],"prefix":"10.1002","volume":"70","author":[{"given":"Shuaibing","family":"Li","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Shenyang Pharmaceutical University  Shenyang China"},{"name":"Laboratory Animal Centre Model Animal and Human Disease Research of Luzhou Key Laboratory Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre Model Animal and Human Disease Research of Luzhou Key Laboratory Southwest Medical University  Luzhou China"},{"name":"Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and School of Pharmacy Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Shenyang Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanye","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre Model Animal and Human Disease Research of Luzhou Key Laboratory Southwest Medical University  Luzhou China"},{"name":"Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and School of Pharmacy Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalian","family":"Qin","sequence":"additional","affiliation":[{"name":"Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and School of Pharmacy Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty Yuen\u2010Kwan","family":"Law","sequence":"additional","affiliation":[{"name":"Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macao Special Administrative Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingni","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Shenyang Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Tang","sequence":"additional","affiliation":[{"name":"Laboratory Animal Centre Model Animal and Human Disease Research of Luzhou Key Laboratory Southwest Medical University  Luzhou China"},{"name":"College of Integeration of Traditional Chinese and Western Medicine &amp; The Affiliated Traditional Chinese Medicine Hospital Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30338\u20107"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(15)70016\u20105"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.03.012"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666170720095240"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010020\u201000221\u20102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001588\u20100"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111428"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00147"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450117666161102121553"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207156"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8030144"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.03.031"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glac136"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00040"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050694"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.7254"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2024.05.036"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30367\u20106"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)60461\u20105"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102548"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3880"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010021\u201000951\u20100"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102846"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.1112"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348\u20100421.2000.tb02556.x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010019\u20101471\u2010y"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11729"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.12.014"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010025\u201001275\u2010w"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010081022\u2010021207"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010024\u201003166\u20109"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010020\u201001886\u20102"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.269"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1492517"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ24\u20100205"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.752"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.5.989"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.032"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.268"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010019\u20101474\u20108"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906\u2010023\u201003970\u20105"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3158\u201009.2009"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)80595\u20104"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010015\u20102608\u20107"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70452","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mnfr.70452","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:55:38Z","timestamp":1776315338000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.70452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mnfr.70452"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.70452","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70452"}}