{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:46:42Z","timestamp":1786866402354,"version":"build-2736575974"},"reference-count":122,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by \u03b2\u2010amyloid (A\u03b2) plaques, neurofibrillary tangles, neuronal cell loss, and oxidative stress. Further deposition of A\u03b2 in the brain induces oxidative stress, neuroinflammation, and memory dysfunction. Hawthorn (<jats:italic>Crataegus pinnatifida<\/jats:italic> Bge.) leaf, a known traditional Chinese medicine, is commonly used for the treatment of hyperlipidemia, heart palpitations, forgetfulness, and tinnitus, and its main bioactive components are Hawthorn Leaf Flavonoids (HLF). In this study, we investigated the neuroprotective effects of the HLF on the A\u03b2<jats:sub>25\u201335<\/jats:sub> (bilateral hippocampus injection) rat model of AD. The results showed that the oral administration of HLF at a dose of 50, 100, and 200\u2009mg\/kg for 30\u2009days significantly ameliorated neuronal cell damage and memory deficits, and markedly increased the enzyme activities of superoxide dismutase and catalase, and the content of glutathione whereas it decreased the malondialdehyde content in the A\u03b2<jats:sub>25\u201335<\/jats:sub> rat model of AD as well as suppressed the activation of astrocytes. In addition, HLF up\u2010regulated Nrf\u20102, NQO\u20101, and HO\u20101 protein expressions. Also, it reduced neuroinflammation by inhibiting activation of astrocytes. In summary, these results indicated that HLF decreased the oxidative stress via activating Nrf\u20102\/antioxidant response element signaling pathways, and may suggest as a potential candidate for AD therapeutic agent.<\/jats:p>","DOI":"10.1002\/ptr.7690","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:26:00Z","timestamp":1669793160000},"page":"1346-1365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuroprotective effects of hawthorn leaf flavonoids in <scp>A\u03b2<sub>25\u201335<\/sub>\u2010induced<\/scp> Alzheimer's disease model"],"prefix":"10.1002","volume":"37","author":[{"given":"Ying","family":"Xu","sequence":"first","affiliation":[{"name":"TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese Medicine  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjiang","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2773-9174","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401818"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955708786369582"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9fo01532a"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf506076n"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.980080612"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2004.07.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-017-0022-z"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-018-08523-5"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527317666180508123050"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00985"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.04.005"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2242"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112884"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathophys.2006.05.004"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105196"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414327200"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16566-1"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.07.013"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305799101"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2014.06.015"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720507779939788"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172398899"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf500067q"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.01.005"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6.2.10971"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-012-1250-4"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.12.011"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.07.001"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4724920"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.04.014"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0955-2863(02)00208-5"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(96)00004-8"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/484613"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(97)01318-8"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990438f"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37111"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules18077549"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.1.76"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.02.046"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/731765"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2018.12.062"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.09.023"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.4314\/tjpr.v19i8.21"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1616-z"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.09.005"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042823"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908397106"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.07.010"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.07.025"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3791\/53308"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advenzreg.2006.01.007"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1270849"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.09.001"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.09.018"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112107"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21567"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.777"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1570-9"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-015-0006-y"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1039\/c8fo02067a"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.05.013"},{"key":"e_1_2_12_64_1","volume-title":"Comparison and analysis of leaf quality of northern hawthorn and Guangxi hawthorn from different places","author":"M Y Y.","year":"2017"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2018.03.003"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1484509"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.54.6.1265"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0301-0082(00)00015-0"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2016.05.039"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002124"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.116.1.201"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1364-6613(00)01664-8"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2018.01.010"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.06.072"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2303"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jnen.0000228136.58062.bf"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.8.759"},{"key":"e_1_2_12_79_1","unstructured":"Patterson C.(2018).World Alzheimer report 2018. The state of the art of dementia research: New frontiers."},{"key":"e_1_2_12_80_1","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos G.","year":"2006"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/pca.820"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad-2007-11202"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2013.10.009"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90547-9"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64010253.x"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10925"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.2007"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e31802d6da9"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.024"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113350"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)02227-9"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1177\/1747493018778713"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2006.07.002"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2018.04.006"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07581.x"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00288"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24081583"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.07.009"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00045"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0297-1"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.04.022"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00296.2009"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0517-0"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02182-3"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05072.x"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7039802"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0255-3"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.01.015"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-2-5-329"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122772"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.3390\/md15030077"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101342"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.4155"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4789196"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-018-2720-1"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8210578"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23040895"},{"key":"e_1_2_12_119_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmy030"},{"key":"e_1_2_12_120_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.7.12.18051"},{"key":"e_1_2_12_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2020.126920"},{"key":"e_1_2_12_122_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmu143"},{"key":"e_1_2_12_123_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7911"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7690","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.7690","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.7690","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T12:21:10Z","timestamp":1692447670000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.7690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,29]]},"references-count":122,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/ptr.7690"],"URL":"https:\/\/doi.org\/10.1002\/ptr.7690","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,29]]},"assertion":[{"value":"2022-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}