{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:06:09Z","timestamp":1782950769349,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Intervertebral disc degeneration (IVDD) has been closely associated with ferroptosis in nucleus pulposus cells (NPCs), the underlying regulatory mechanisms and therapeutic strategies remain poorly defined. This study aims to delineate how ginsenoside Rg3 mitigates IVDD progression through ferroptosis suppression, providing a basis for clinical translation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>An erastin\u2010induced nucleus pulposus cell ferroptosis model was established. Suitable Erastin concentrations (0\u201320\u2009\u03bcM) were screened via CCK\u20108, qRT\u2010PCR, and Western blotting based on viability, extracellular matrix (COL2A1\/ACAN\/ADAMTS5\/MMP3) and ferroptosis markers (GPX4\/FTH\u20101\/ACSL4), followed by determination of optimal Rg3 concentrations (0\u2013150\u2009\u03bcM) using identical methods. Key targets of Rg3 were predicted through network pharmacology and verified by qRT\u2010PCR and Western blotting. After establishing a rat tail puncture\u2010induced IVDD model, local injection of Rg3 was administered. Therapeutic efficacy was evaluated by MRI assessment of nucleus pulposus status and disc height, alongside histological and immunohistochemical analyses of Rg3's role in delaying disc degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>5\u2009\u03bcM Erastin effectively induced ferroptosis in nucleus pulposus cells, reducing cell viability, suppressing expression of extracellular matrix anabolic proteins (COL2A1, ACAN), while promoting catabolic factors (MMP3, ADAMTS5) and downregulating ferroptosis inhibitors (GPX4, FTH\u20101). These alterations were significantly reversed by 100\u2009\u03bcM Rg3. Integrated network pharmacology and molecular biological validation identified PRKAA2 as the key target mediating Rg3's anti\u2010degenerative effects. In\u00a0vivo rat experiments demonstrated that Rg3 treatment preserved disc height and attenuated disc degeneration, with histological and immunohistochemical analyses further confirming its therapeutic efficacy and PRKAA2\u2010targeted regulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study elucidates the therapeutic mechanism of Rg3 in delaying IVDD progression via PRKAA2\u2010mediated ferroptosis inhibition, providing substantial experimental evidence for its clinical translation as a potential disease\u2010modifying agent.<\/jats:p><\/jats:sec>","DOI":"10.1111\/os.70150","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T10:35:03Z","timestamp":1756118103000},"page":"2960-2972","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Ferroptosis With Ginsenoside Rg3 Alleviates Intervertebral Disc Degeneration"],"prefix":"10.1111","volume":"17","author":[{"given":"Weiran","family":"Xu","sequence":"first","affiliation":[{"name":"School of Basic Medicine Sciences North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences North China University of Science and Technology  Tangshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Spine Surgery Tianjin Hospital, Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7274-6951","authenticated-orcid":false,"given":"Yinhuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences North China University of Science and 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