{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:50:26Z","timestamp":1788184226887,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22507128"],"award-info":[{"award-number":["22507128"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["22507128"],"award-info":[{"award-number":["22507128"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Gansu Longyuan Youth Talents Program","award":["842024017"],"award-info":[{"award-number":["842024017"]}]},{"name":"Basic Research Program of Gansu Province","award":["26JRRA026"],"award-info":[{"award-number":["26JRRA026"]}]},{"name":"Gansu Province Youth Talent Project","award":["2026QNTD004"],"award-info":[{"award-number":["2026QNTD004"]}]},{"name":"Yunnan Characteristic Plant Screening and R&D Service CXO Platform","award":["2022YKZY001"],"award-info":[{"award-number":["2022YKZY001"]}]},{"name":"Key Research and Development Project of Yunnan Province","award":["202203AC100009"],"award-info":[{"award-number":["202203AC100009"]}]},{"DOI":"10.13039\/501100008871","name":"Yunnan Provincial Science and Technology Department","doi-asserted-by":"crossref","award":["202302AA310035"],"award-info":[{"award-number":["202302AA310035"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"crossref"}]},{"award":["202302AA310035"],"award-info":[{"award-number":["202302AA310035"]}],"id":[{"id":"https:\/\/ror.org\/03whqdf70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Autophagy dysfunction is implicated in the pathogenesis of Alzheimer\u2019s disease (AD), and enhancing autophagic flux has been proposed as a potential strategy for addressing neurodegenerative diseases. To expand the structural diversity of ingenol esters and systematically evaluate their autophagic flux activation activity, a systematic phytochemical investigation of ingenane diterpenoids from Euphorbia peplus was conducted. A total of 13 ingenane-type compounds were isolated and identified, including two previously undescribed compounds, euphingenol A and B (1\u20132), together with 11 known analogs (3\u201313). Their structures were elucidated by extensive spectroscopic analyses (HRESIMS and NMR) and comparison with literature data. The compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. 17-O-benzoyl-20-deoxyingenol (3) significantly activated autophagic flux at concentrations of 10 \u03bcM and 40 \u03bcM, while euphingenol A (1) induced a dose-dependent increase, with structure-activity relationship analysis indicating that C-17 acylation enhances this bioactivity. These findings suggest that compound 3 warrants further investigation as a potential modulator of autophagic flux, possibly through binding to PKC\u03b4 (protein kinase C), with relevance to autophagy-related neurodegenerative conditions.<\/jats:p>","DOI":"10.3390\/molecules31091388","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ingenane Diterpenoids from Euphorbia peplus: Structure Elucidation and Autophagic Flux Activation Activity"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9303-9195","authenticated-orcid":false,"given":"Jiajia","family":"Wan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7947-8610","authenticated-orcid":false,"given":"Zifei","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9496-2152","authenticated-orcid":false,"given":"Xiaojiang","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"},{"name":"Yunnan Characteristic Plant Extraction Laboratory, Kunming 650106, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4472-7079","authenticated-orcid":false,"given":"Rongcan","family":"Luo","sequence":"additional","affiliation":[{"name":"Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730099, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5766-0198","authenticated-orcid":false,"given":"Yingtong","family":"Di","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrn3961","article-title":"Compromised autophagy and neurodegenerative diseases","volume":"16","author":"Menzies","year":"2015","journal-title":"Nat. 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