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Their structures including absolute configurations were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Biological evaluation revealed that compounds 4 and 16 showed potential as dual-target anti-Alzheimer\u2019s disease (AD) lead compounds, as they not only exhibited potent acetylcholinesterase (AChE) inhibitory activities but also induced peroxisome proliferator-activated receptor-\u03b3 transactivation and upregulated ATP-binding cassette transporter A1 expression. The in vivo anti-AD effects of 4 and 16 were evaluated by the zebrafish behavioral experiments. Compound 16 exhibited anti-AD effects with no detectable toxicity or teratogenicity, whereas 4 exhibited toxicity to zebrafish at 10 \u03bcM. These findings not only expand the chemical diversity of spiro-PPAPs but also underscore their potential as dual-target agents for AD treatment.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.6c00583","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:04:37Z","timestamp":1786550677000},"page":"2486-2501","source":"Crossref","is-referenced-by-count":0,"title":["Spiro-Polycyclic Polyprenylated Acylphloroglucinols from\n                    <i>Hypericum monogynum<\/i>\n                    and Their anti-Alzheimer\u2019s Disease Effects"],"prefix":"10.1021","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4023-922X","authenticated-orcid":true,"given":"Wenjing","family":"Tian","sequence":"first","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoulun","family":"He","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjiya","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-4821","authenticated-orcid":true,"given":"Junjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Qilu University of Technology (Shandong Academy of Sciences) , , ,","place":["Jinan, China, 250103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchun","family":"Du","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhang","family":"You","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingting","family":"Lin","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Li","sequence":"additional","affiliation":[{"name":"Qilu University of Technology (Shandong Academy of Sciences) , , ,","place":["Jinan, China, 250103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-7893","authenticated-orcid":true,"given":"Haifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Xiamen University , , ,","place":["Xiamen, People\u2019s Republic of China, 361102"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026100909075599000_cit1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. 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