淫羊藿素靶向调控PRDX1-MAPK信号轴改善化疗后间充质干细胞的造血支持功能

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

淫羊藿素靶向调控PRDX1-MAPK信号轴改善化疗后间充质干细胞的造血支持功能

Pengli Huang ^a^,^# ,
Rui Jing ^b^,^# ,
Wendan Zhang ^c^,^# ,
Jun Xia ^d^,^e^,^# ,
Xin Luan ^a ,
Ji Ye ^b ,
Saisai Tian ^b ,
Hao Zhang ^a ,
Qun Wang ^a ,
Honghong Jiang ^c ,
Ningbo Wu ^f ,
Mengting Xu ^a ,
Guangyong Zheng ^a ,
Dong Lu ^a ,
Fei Qian ^a ,
Tao Cheng ^g ,
Weian Yuan ^h ,
Feng Liu ^d^,^e^,ⁱ^,^* ,
Sanhong Liu ^a^,^* ,
Weidong Zhang ^b^,^j^,^*

作者信息 +

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

Pengli Huang ^a^,^# ,
Rui Jing ^b^,^# ,
Wendan Zhang ^c^,^# ,
Jun Xia ^d^,^e^,^# ,
Xin Luan ^a ,
Ji Ye ^b ,
Saisai Tian ^b ,
Hao Zhang ^a ,
Qun Wang ^a ,
Honghong Jiang ^c ,
Ningbo Wu ^f ,
Mengting Xu ^a ,
Guangyong Zheng ^a ,
Dong Lu ^a ,
Fei Qian ^a ,
Tao Cheng ^g ,
Weian Yuan ^h ,
Feng Liu ^d^,^e^,ⁱ^,^* ,
Sanhong Liu ^a^,^* ,
Weidong Zhang ^b^,^j^,^*

Author information +

^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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文章历史 +

Received	Accepted	Published
2025-06-01	2025-08-06
Issue Date
2025-08-21

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摘要

缓解化疗所致的骨髓抑制是持续有效抗癌治疗的重要组成部分。尽管造血微环境在调控造血干/祖细胞（hematopoietic stem/progenitor cells,HSPCs）中的作用已被广泛研究，但目前尚无通过靶向调控造血微环境来改善造血功能的药物应用于临床。本研究显示，来自中药淫羊藿的活性小分子淫羊藿素（icaritin，ICT）能在小鼠和斑马鱼模型中有效缓解化疗导致的血细胞减少。我们证实ICT可提升HSPCs的数量和造血功能，且这种有益作用是通过间接方式实现的。单细胞测序分析证明ICT在骨髓微环境中的靶细胞为间充质干细胞（mesenchymal stromal cells，MSCs）。此外，研究鉴定出过氧化还原酶1（peroxiredoxin 1，PRDX1）是ICT的直接作用靶点。ICT通过PRDX1-活性氧（reactive oxygen species ，ROS）-丝裂原活化蛋白激酶（mitogen-activated protein kinase ，MAPK）信号轴刺激MCSs表达效应分子CXC趋化因子配体12（C–X–C motif chemokine ligand 12，CXCL12），从而增强HSPCs的数量和功能。这些结果表明，ICT是一种有望通过靶向调控造血微环境来恢复化疗后造血功能的化合物。

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.

关键词

淫羊藿素 / 骨髓抑制 / 间充质干细胞 / 过氧化还原酶1 / CXC趋化因子配体12

Key words

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

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引用格式 ▾

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. 淫羊藿素靶向调控PRDX1-MAPK信号轴改善化疗后间充质干细胞的造血支持功能[J]. 工程（英文）, 2025, 54(11): 261-276 DOI:10.1016/j.eng.2025.08.019