{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:45:14Z","timestamp":1791769514767,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T00:00:00Z","timestamp":1791676800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104902"],"award-info":[{"award-number":["82104902"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374380"],"award-info":[{"award-number":["82374380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diabetic osteoporosis (DOP) is characterized by chronic low\u2010grade inflammation and impaired bone formation. Pinoresinol diglucoside (PDG), a bioactive compound derived from\n                    <jats:italic>Eucommia ulmoides<\/jats:italic>\n                    Oliv., has shown therapeutic potential in metabolic bone disorders; however, its direct molecular targets and integrated mechanisms remain unclear. This study aimed to elucidate the metabolic basis and molecular targets through which PDG protects against high glucose (HG)\u2010induced osteoblast dysfunction and diabetic bone loss. Osteogenic effects of PDG were evaluated in HG\u2010exposed osteoblasts, with untargeted metabolomics, qPCR, Western blotting, molecular docking, SPR, and siRNA\u2010mediated knockdown applied to identify altered pathways and validate target necessity. In\u00a0vivo, PDG was administered to db\/db mice with DOP for 8\u2009weeks, followed by micro\u2010CT, bone metabolism factors, histomorphometry, and immunofluorescence analyses. Metabolomic profiling identified arachidonic acid metabolism as the central pathway dysregulated in HG conditions and rescued by PDG. PDG directly bound and inhibited both p65 (NF\u2010\u03baB) and GSK3\u03b2. Mechanistically, p65 knockdown abolished the anti\u2010inflammatory effect of PDG without affecting osteogenesis, whereas GSK3\u03b2 knockdown abrogated \u03b2\u2010catenin activation and osteogenic differentiation without affecting anti\u2010inflammatory responses, indicating that they function as parallel and independent branches. Simultaneous knockdown of both completely blocked the functional recovery of osteoblast differentiation. In DOP mice, PDG significantly improved trabecular microarchitecture and bone metabolic homeostasis, reduced local PGE2 levels with an effect directly targeting bone, inhibited p65 nuclear translocation, and restored \u03b2\u2010catenin nuclear localization. PDG ameliorates DOP by dual targeting p65 and GSK3\u03b2, coordinately inhibiting NF\u2010\u03baB\u2010mediated inflammation and activating the \u03b2\u2010catenin osteogenic program, highlighting its therapeutic potential for DOP.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70468","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:16:13Z","timestamp":1791767773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Arachidonic Acid Metabolism by Pinoresinol Diglucoside Ameliorates Osteogenic Dysfunction via Coordinated\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Suppression and\n                    <scp>GSK3\u03b2<\/scp>\n                    \/\u03b2\u2010Catenin Activation in Diabetic 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