{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:15:39Z","timestamp":1785417339883,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Heilongjiang Natural Science Foundation","doi-asserted-by":"publisher","award":["ZD2023C004"],"award-info":[{"award-number":["ZD2023C004"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371840 and 82001113"],"award-info":[{"award-number":["32371840 and 82001113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32371840 and 82001113"],"award-info":[{"award-number":["32371840 and 82001113"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder for which no effective treatments are currently available. PANoptosis is a coordinated cell death pathway involving pyroptosis, apoptosis, and necroptosis. Astragaloside IV (AS-IV) is a bioactive saponin derived from Astragalus membranaceus. Behavioral performance was evaluated using the Morris water maze and open field tests, while neuronal damage was assessed by Nissl staining. The expression levels of A\u03b2, IL-18, and PANoptosis-related proteins were analyzed by Western blot. Immunofluorescence was performed to assess the co-localization of PANoptosis-associated proteins with neurons in the hippocampal region. In addition, the effects of AS-IV on the expression of PANoptosis-related proteins were examined in A\u03b2-induced HT22 cells. AS-IV improved spatial memory performance and alleviated anxiety-like behaviors in AD mice. Furthermore, AS-IV treatment significantly reduced A\u03b2 protein levels and attenuated neuronal loss in the hippocampus. Key markers of PANoptosis were downregulated following AS-IV treatment. Immunofluorescence revealed strong co-localization between PANoptosis-associated proteins and neurons. In vitro, AS-IV also inhibited the A\u03b2-induced upregulation of PANoptosis-related proteins in HT22 cells. Collectively, these results indicate that AS-IV exerts neuroprotective effects in AD models, which may be associated with reduced A\u03b2 protein deposition, attenuated neuronal loss, and the regulation of PANoptosis-related proteins in the hippocampus.<\/jats:p>","DOI":"10.3390\/ijms27083508","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:24:58Z","timestamp":1776176698000},"page":"3508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragaloside IV Improves Cognitive Impairment in Alzheimer\u2019s Mice by Alleviating Neuron PANoptosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Weihai","family":"Wang","sequence":"first","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojie","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4521-3320","authenticated-orcid":false,"given":"Chunsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science, Northeast Forestry University, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a006148","DOI":"10.1101\/cshperspect.a006148","article-title":"The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment","volume":"2","author":"Tarawneh","year":"2012","journal-title":"Cold Spring Harb. 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