{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:52:17Z","timestamp":1787979137444,"version":"build-2784847793"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003065","name":"Universit\u00e4t Wien","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Chronic neuroinflammation and impaired proteostasis are increasingly recognized as interconnected drivers of Parkinson\u2019s disease (PD). Due to their pleiotropic character, multicomponent herbal remedies combining anti-inflammatory and proteostatic activity may counteract these disease-promoting processes. This study investigated a hydroethanolic extract of\n                      <jats:italic>Filipendula ulmaria<\/jats:italic>\n                      (FE) for its ability to modulate neuroinflammation, proteostasis, and aging-associated mechanisms relevant to PD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of FE on lifespan and health span were assessed in wild-type and on \u03b1-syn::YFP fluorescence, survival and thermoresistance in transgenic NL5901\n                      <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                      . FE was fractionated by flash chromatography, and bioactivity was assigned to individual constituents using LC-MS dereplication and a\n                      <jats:sup>1<\/jats:sup>\n                      H NMR-based biochemometric approach. Identified constituents were further examined for their capacity to reduce \u03b1-syn::YFP fluorescence and enhance thermotolerance in NL5901. To assess their relevance in neuroinflammation, all samples were examined in LPS-stimulated human microglial HMC3 cells for their effects on pro-inflammatory gene expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FE extended lifespan, improved health span and reduced \u03b1-syn::YFP fluorescence in NL5901 by up to 25% at 200\u00a0\u03bcg\/mL. In HMC3 cells, FE significantly downregulated\n                      <jats:italic>IL-1\u03b2<\/jats:italic>\n                      ,\n                      <jats:italic>IL-6<\/jats:italic>\n                      , and\n                      <jats:italic>MCP-1<\/jats:italic>\n                      expression at 100\u00a0\u03bcg\/mL without cytotoxicity. Biochemometric and LC-MS analyses identified the flavonoid glycosides spiraeoside and miquelianin as key constituents, reducing the \u03b1-syn::YFP fluorescence by 32% and 35% at 200 \u03bcg\/mL, respectively, while simultaneously increasing thermotolerance in NL5901 and suppressing pro-inflammatory cytokine expression in microglia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FE represents a promising source of neuroprotective agents targeting both neuroinflammation and proteostasis, supporting spiraeoside and miquelianin as hit candidates for preventive strategies against early neurodegenerative mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1720314","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T10:48:27Z","timestamp":1770806907000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Miquelianin and spiraeoside from Filipendula ulmaria mitigate \u03b1-synuclein accumulation in C.elegans and reduce the expression of neuroinflammatory cytokines in human microglia"],"prefix":"10.3389","volume":"16","author":[{"given":"Martina","family":"Redl","sequence":"first","affiliation":[{"name":"Division of Pharmacognosy, Department of Pharmaceutical Sciences, University of Vienna","place":["Vienna, Austria"]},{"name":"Vienna Doctoral School of Pharmaceutical, Nutritional, and Sport Sciences, University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Weisenburger","sequence":"additional","affiliation":[{"name":"Preclinical R&D, Dr. Willmar Schwabe GmbH and Co. 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