Icaritin Improves the Hematopoiesis-Supportive Function of MSCs via A PRDX1–MAPK Axis After Chemotherapy
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.
Authors
- Wendan Zhang (ORCID: https://orcid.org/0009-0004-1081-4515)
- Sai Tian (ORCID: https://orcid.org/0000-0003-2498-190X)
- Jun Xia (ORCID: https://orcid.org/0000-0001-7331-0673)
- Mengting Xu (ORCID: https://orcid.org/0000-0002-6751-1986)
- Ningbo Wu (ORCID: https://orcid.org/0000-0002-9900-4401)
- Sanhong Liu (ORCID: https://orcid.org/0000-0002-8695-0343)
- Pengli Huang
- Lu Dong (ORCID: https://orcid.org/0000-0001-6737-1381)
- Honghong Jiang
- Xin Luan (ORCID: https://orcid.org/0000-0003-3674-256X)
- Liyang Zhang (ORCID: https://orcid.org/0000-0002-4054-1667)
- Feng Liu (ORCID: https://orcid.org/0000-0002-5572-8512)
- Wei-An Yuan (ORCID: https://orcid.org/0009-0009-9318-2547)
- Rui Jing (ORCID: https://orcid.org/0000-0002-1758-7093)
- Guangyong Zheng (ORCID: https://orcid.org/0009-0004-5392-7165)
- Qian Fei (ORCID: https://orcid.org/0000-0002-6643-7681)
- Tao Cheng (ORCID: https://orcid.org/0000-0003-4395-1095)
- Weidong Zhang
- Ji Ye (ORCID: https://orcid.org/0000-0002-1201-3971)
- Qun Wang (ORCID: https://orcid.org/0000-0003-1014-8677)
Institutions
- Shandong University (CN)
- Second Military Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Chinese PLA General Hospital (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Institute of Hematology & Blood Diseases Hospital (CN)
- Shuguang Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Zoology (CN)
Publication Details
- Journal
- Engineering
- Published
- 2025-08-22
- DOI
- https://doi.org/10.1016/j.eng.2025.08.019
- Citations
- 1
- Primary Topic
- Medicinal Plant Pharmacodynamics Research
- Type
- article
- Field-Weighted Citation Impact
- 1.56