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However, oxidative attack induced by various physiopathological stresses always compromises HSC maintenance, while there remains lack of safe and effective antioxidative measures combating these conditions. Here, we show that ferulic acid (FA), a natural antioxidant abundantly present in Angelica sinensis which is a traditional Chinese herb commonly used for promotion of blood production, distinctively and directly promotes HSC maintenance and thereby boosts hematopoiesis at homeostasis, whether supplemented over the long term in vivo or in HSC culture ex vivo. Using a mouse model of acute myelosuppressive injury induced by ionizing radiation, we further reveal that FA supplementation effectively safeguards HSC maintenance and accelerates hematopoietic regeneration after acute myelosuppressive injury. Mechanistically, FA diminishes ferroptosis susceptibility of HSCs through limiting the labile iron pool (LIP), thus favoring HSC maintenance. In addition, the LIP limitation and anti-ferroptosis activity of FA is independent of nuclear-factor erythroid 2-related factor 2 (NRF2), probably relying on its iron-chelating ability. These findings not only uncover a novel pharmacological action and mechanism of FA in promoting HSC maintenance, but also provides a therapeutic rationale for using FA or FA-rich herbs to treat iron overload- and ferroptosis-associated pathologies such as acute myelosuppressive injury.<\/jats:p>","DOI":"10.3390\/antiox14091053","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:49:34Z","timestamp":1756309774000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility"],"prefix":"10.3390","volume":"14","author":[{"given":"Shuzhen","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Le","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"},{"name":"Frontier Medical Training Brigade, Army Medical University (Third Military Medical University), Changji 831200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"},{"name":"Frontier Medical Training Brigade, Army Medical University (Third Military Medical University), Changji 831200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junping","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-0325","authenticated-orcid":false,"given":"Changhong","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing 400038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.stem.2023.09.013","article-title":"Hematopoietic stem cells through the ages: A lifetime of adaptation to organismal demands","volume":"30","author":"Kasbekar","year":"2023","journal-title":"Cell Stem 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