Icaritin Improves the Hematopoiesis-Supportive Function of MSCs via A PRDX1

Engineering ›› 2025, Vol. 54 ›› Issue (11) : 261 -276. DOI: 10.1016/j.eng.2025.08.019

Article

Icaritin Improves the Hematopoiesis-Supportive Function of MSCs via A PRDX1–MAPK Axis After Chemotherapy

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^aState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^bDepartment of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

^cFaculty of Pediatrics, the Seventh Medical Center, Beijing Key Laboratory of Pediatric Organ Failure, National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Chinese PLA General Hospital, Beijing 100700, China

^dState Key Laboratory of Organ Regeneration and Reconstruction, Beijing Institute for Stem Cell and Regenerative Medicine, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

^eUniversity of Chinese Academy of Sciences, Beijing 100049, China

^fShanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

^gInstitute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China

^hShuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

ⁱSchool of Life Sciences, Shandong University, Qingdao 266237, China

^jInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China

* E-mail address: liuf@sdu.edu.cn

* E-mail address: liush@shutcm.edu.cn

* E-mail address: wdzhangy@smmu.edu.cn

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Received	Accepted	Published
2025-06-01	2025-08-06	2025-08-21
Issue Date	Revised Date
2025-08-21	2025-07-15

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Abstract

The alleviation of chemotherapy-induced myelosuppression is an integral part of sustained and effective cancer therapy. Although the role of the hematopoietic microenvironment in the regulation of hematopoietic stem/progenitor cells (HSPCs) has been widely studied, no drugs that improve hematopoiesis by targeting and modulating the hematopoietic microenvironment have been used clinically. Here, we show that the active small molecule icaritin (ICT) from the Chinese herb Epimedium brevicornum Maxim effectively alleviates chemotherapy-induced hemocytopenia in both mouse and zebrafish models. We demonstrated that ICT enhanced the number and hematopoietic function of HSPCs and that the beneficial effects of ICT occurred indirectly. Single-cell sequencing analysis confirmed that the target cells of ICT in the bone marrow microenvironment were mesenchymal stromal cells (MSCs). In addition, peroxiredoxin 1 (PRDX1) was identified as a direct target of ICT. Furthermore, ICT stimulated MSCs to express the effector molecule C–X–C motif chemokine ligand 12 (CXCL12) through the PRDX1–reactive oxygen species (ROS)–mitogen-activated protein kinase (MAPK) signaling axis, thereby increasing the number and function of HSPCs. These results suggest that ICT is a promising compound for achieving targeted modulation of the hematopoietic microenvironment to restore hematopoiesis after chemotherapy.

Keywords

Icaritin / Myelosuppression / Mesenchymal stromal cells / Peroxiredoxin 1 / C–X–C motif chemokine ligand 12

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Pengli Huang, Rui Jing, Wendan Zhang, Jun Xia, Xin Luan, Ji Ye, Saisai Tian, Hao Zhang, Qun Wang, Honghong Jiang, Ningbo Wu, Mengting Xu, Guangyong Zheng, Dong Lu, Fei Qian, Tao Cheng, Weian Yuan, Feng Liu, Sanhong Liu, Weidong Zhang. Icaritin Improves the Hematopoiesis-Supportive Function of MSCs via A PRDX1–MAPK Axis After Chemotherapy. Engineering, 2025, 54(11): 261-276 DOI:10.1016/j.eng.2025.08.019

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