{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:18:09Z","timestamp":1790720289784,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Introduction<\/jats:title>\n \n Selaginella<\/jats:italic>\n species hold a traditional place in medicine and cosmetics, but their potential to extend lifespan and the underlying bioactive compounds remain inadequately investigated. This study aims to systematically evaluate the anti-aging properties of diverse Selaginella extracts and to identify the key bioactive components and mechanisms involved.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We collected 23\n Selaginella<\/jats:italic>\n samples from 13 different provinces across China to assess their geographical influence. Two representative methanol extracts, S4 (high in amentoflavone) and S16 (low in amentoflavone), were selected for in-depth evaluation using the\n Caenorhabditis elegans<\/jats:italic>\n model. We employed lifespan assays, stress resistance tests, and comparative transcriptomics to analyze the effects on longevity, and pathway modulation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both S4 and S16 extracts significantly extended the lifespan of\n C. elegans<\/jats:italic>\n under normal conditions and modulated conserved longevity pathways, including MAPK and FOXO signaling, with daf-16 and\n egl-8<\/jats:italic>\n emerging as key hub genes. Amentoflavone was identified and validated as a critical bioactive component, which alone extended lifespan by 63.81% and enhanced stress resistance. Mechanistically, amentoflavone promoted the nuclear translocation of DAF-16 and up-regulated the expression of antioxidant genes (e.g.,\n sod-3<\/jats:italic>\n ,\n gst-3\/4<\/jats:italic>\n ,\n hsp-16.48\/12.6<\/jats:italic>\n ), leading to a significant reduction in intracellular ROS levels.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n Our findings demonstrate that\n Selaginella<\/jats:italic>\n extract and its key component, amentoflavone, delay aging primarily by activating the DAF-16\/FOXO transcription factor and bolstering the antioxidant defense system. This study not only highlights amentoflavone as a major contributor to the lifespan-extending effects of Selaginella but also underscores the potential of these natural compounds as promising agents for healthy aging.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2025.1658991","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T13:39:41Z","timestamp":1764077981000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Selaginella extracts extend lifespan and mitigate oxidative stress in Caenorhabditis elegans"],"prefix":"10.3389","volume":"16","author":[{"given":"Xueqing","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjian","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Gou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"114444","DOI":"10.1016\/j.jep.2021.114444","article-title":"The traditional and modern uses of Selaginella tamariscina (P. 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