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Antioxidants
Volume 14
Issue 9
10.3390/antiox14091053
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility

by
Shuzhen Zhang
1,†,
Yimin Zhang
1,†,
Jiacheng Le
1,
Kuan Yu
1,
Xinliang Chen
1,
Jun Chen
1,
Mo Chen
1,
Yiding Wu
1,2,
Yang Xu
1,
Song Wang
1,
Chaonan Liu
1,2,
Junping Wang
1,* and
Changhong Du
1,*
1
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
2
Frontier Medical Training Brigade, Army Medical University (Third Military Medical University), Xinjiang 831200, China
*
Authors to whom correspondence should be addressed.
†
These authors contribute equally to this manuscript.
Antioxidants 2025, 14(9), 1053; https://doi.org/10.3390/antiox14091053
Submission received: 26 July 2025 / Revised: 23 August 2025 / Accepted: 25 August 2025 / Published: 27 August 2025
(This article belongs to the Special Issue Natural Products: Biological, Antioxidant Properties and Health Effects—4th Edition)
Versions Notes

Abstract

Redox balance is essential for maintenance of the hematopoietic stem cell (HSC) pool, which ensures the lifelong hematopoiesis. 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.
Keywords: ferulic acid; hematopoietic stem cell; ferroptosis; iron; ionizing radiation; myelosuppression ferulic acid; hematopoietic stem cell; ferroptosis; iron; ionizing radiation; myelosuppression

Share and Cite

MDPI and ACS Style

Zhang, S.; Zhang, Y.; Le, J.; Yu, K.; Chen, X.; Chen, J.; Chen, M.; Wu, Y.; Xu, Y.; Wang, S.; et al. Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility. Antioxidants 2025, 14, 1053. https://doi.org/10.3390/antiox14091053

AMA Style

Zhang S, Zhang Y, Le J, Yu K, Chen X, Chen J, Chen M, Wu Y, Xu Y, Wang S, et al. Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility. Antioxidants. 2025; 14(9):1053. https://doi.org/10.3390/antiox14091053

Chicago/Turabian Style

Zhang, Shuzhen, Yimin Zhang, Jiacheng Le, Kuan Yu, Xinliang Chen, Jun Chen, Mo Chen, Yiding Wu, Yang Xu, Song Wang, and et al. 2025. "Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility" Antioxidants 14, no. 9: 1053. https://doi.org/10.3390/antiox14091053

APA Style

Zhang, S., Zhang, Y., Le, J., Yu, K., Chen, X., Chen, J., Chen, M., Wu, Y., Xu, Y., Wang, S., Liu, C., Wang, J., & Du, C. (2025). Ferulic Acid Promotes Hematopoietic Stem Cell Maintenance in Homeostasis and Injury Through Diminishing Ferroptosis Susceptibility. Antioxidants, 14(9), 1053. https://doi.org/10.3390/antiox14091053

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