{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:46:17Z","timestamp":1775108777570,"version":"3.50.1"},"reference-count":154,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Research and Operational Expenses Research Project of Provincial Higher Education Institutions in Heilongjiang Province","award":["2024-KYYWF-0597.2"],"award-info":[{"award-number":["2024-KYYWF-0597.2"]}]},{"name":"Creative team of Jiamusi University","award":["JMSUHXXM20230703001"],"award-info":[{"award-number":["JMSUHXXM20230703001"]}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["PL2024H010"],"award-info":[{"award-number":["PL2024H010"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Notably, certain ginsenoside components exhibit distinct bidirectional and context-dependent regulatory effects on ferroptosis depending on the disease setting. In aberrantly proliferating or activated cells, ginsenosides function as ferroptosis inducers, whereas in damaged quiescent cells of normal tissues, they act as ferroptosis inhibitors. The pro-ferroptotic effect is predominantly observed in cells characterized by abnormal proliferation or activation, such as cancer cells and activated hepatic stellate cells in liver fibrosis. In this context, ginsenosides modulate key iron metabolism proteins and suppress antioxidant defense systems (e.g., GPX4, SLC7A11), thereby triggering intracellular iron overload and explosive lipid peroxidation, ultimately culminating in ferroptosis. Conversely, the anti-ferroptotic effect primarily targets damaged non-proliferative cells in normal tissues subjected to pathological insults (e.g., ischemia\u2013reperfusion, inflammation). In this setting, the regulatory focus of ginsenosides shifts toward maintaining iron homeostasis through mechanisms including upregulation of iron storage proteins (e.g., FTH1), downregulation of iron uptake proteins (e.g., TFRC), and inhibition of labile Fe2+ accumulation, thereby blocking ferroptosis initiation. This review systematically elucidates the pharmacological effects and underlying mechanisms by which different ginsenoside components regulate ferroptosis across various disease contexts and cell types, with particular emphasis on their disease- and cell type-dependent bidirectional regulatory characteristics. By highlighting these context-specific effects, we aim to provide novel potential therapeutic targets and mechanistic insights for the precision treatment of diverse pathological conditions, including malignant proliferative disorders, non-malignant aberrantly activated\/proliferative diseases such as liver fibrosis, and cell injury\/degenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms27073172","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"3172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside-Mediated Ferroptosis Regulation: Bidirectional Effects and Therapeutic Potential in Diseases"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5203-564X","authenticated-orcid":false,"given":"Yuanyuan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7648-2577","authenticated-orcid":false,"given":"Mengxue","family":"Song","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7747-0803","authenticated-orcid":false,"given":"Huizhen","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6169-9180","authenticated-orcid":false,"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Jiamusi University, Jiamusi 154007, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.5582\/bst.2021.01318","article-title":"The positive role of traditional Chinese medicine as an adjunctive therapy for cancer","volume":"15","author":"Zhang","year":"2021","journal-title":"Biosci. 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