{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T09:45:31Z","timestamp":1782812731904,"version":"3.54.5"},"reference-count":62,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"High-level University Construction Fund of Guangdong Province","award":["06-410-2107217"],"award-info":[{"award-number":["06-410-2107217"]}]},{"name":"High-level University Construction Fund of Guangdong Province","award":["YXY2021A05"],"award-info":[{"award-number":["YXY2021A05"]}]},{"name":"Scientific and Technological Planning Program of Guangzhou","award":["1201610286"],"award-info":[{"award-number":["1201610286"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515010903"],"award-info":[{"award-number":["2019A1515010903"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secoisolariciresinol diglucoside (SDG), a phytoestrogen, has been demonstrated to exert anti-inflammatory and neuroprotective effects. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) serves as a critical negative regulator of MAPK signaling pathways, and the MAPK signaling pathways play a significant role in the pathogenesis of Alzheimer's disease (AD). However, it remains unclear whether SDG ameliorates Alzheimer-like lesions by regulating the MAPK pathway through increasing MKP-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to investigate the impact of SDG on the Alzheimer-like lesions of AD mice and its mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three-month-old 5\u00d7FAD mice were treated with SDG (50\u2005mg\u00b7kg-1\u00b7d-1, i.g.) for 2 months. Learning and spatial memory function was assessed with the behavioral test. Immunofluorescence and Thioflavine-S staining was assessed with the levels of amyloid-\u03b2 (A\u03b2) plaques in the cortex and hippocampus. Western blot was performed to evaluate the level of learning memory-related proteins, hyperphosphorylated tau, APP-related proteins, and MAPK phosphorylation. Besides, knockdown of MKP-1 in N2A\/APP cells to investigate whether SDG regulates the MAPK signaling pathway by increasing MKP-1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that SDG significantly enhanced learning and spatial memory while recovering PSD95, PKA-C\u03b1, and synaptophysin levels in 5\u00d7FAD mice. SDG reduced A\u03b2 plaques, tau phosphorylation at Ser 199\/214\/262\/396 and Thr 231, alleviated the phosphorylation of MAPKs (JNK, ERK1\/2, P38), and increased p-GSK-3\u03b2 (Ser9), while decreased activation of microglia (Iba-1) and astrocytes (GFAP). Moreover, knockdown of MKP-1 in N2A\/APP cells inhibited the regulatory effect of SDG on APP, ERK1\/2 and JNK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SDG ameliorates Alzheimer-like lesions may be related with increasing MKP-1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261450557","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:23:52Z","timestamp":1780475032000},"page":"256-272","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Secoisolariciresinol diglucoside ameliorates Alzheimer-like lesions by increasing MKP-1"],"prefix":"10.1177","volume":"112","author":[{"given":"Mei","family":"Chen","sequence":"first","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangtai","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Jinan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-4451","authenticated-orcid":false,"given":"Yinghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01382-x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2024.09.042"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00397-x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00264-X"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990801)57:3<399::AID-JNR12>3.0.CO;2-W"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190507"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0132-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1202-06.2006"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00157"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02171-2"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5122(98)00108-X"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2020.1863356"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3961445"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26102954"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154056"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.219049"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000000290"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114509990201"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.5650\/jos.ess13135"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-015-0059-3"},{"key":"e_1_3_3_24_2","first-page":"897","article-title":"Morris water maze experiment","volume":"19","author":"Nunez J","year":"2008","unstructured":"Nunez J. 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