2. Academic Validation
  3. Oxymatrine boosts hematopoietic regeneration by modulating MAPK/ERK phosphorylation after irradiation-induced hematopoietic injury

Oxymatrine boosts hematopoietic regeneration by modulating MAPK/ERK phosphorylation after irradiation-induced hematopoietic injury

  • Exp Cell Res. 2023 Apr 17;113603. doi: 10.1016/j.yexcr.2023.113603.
Lijing Yang 1,  Yukai Lu 2,  Zihao Zhang 3,  Yin Chen 4,  Naicheng Chen 5,  Fang Chen 6,  Yan Qi 7,  Changhao Han 8,  Yang Xu 9,  Mo Chen 10,  Mingqiang Shen 11,  Song Wang 12,  Hao Zeng 13,  Yongping Su 14,  Mengjia Hu 15,  Junping Wang 16
Affiliations

Affiliations

  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: yanglijing1997@sina.com.
  • 2 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: luyukai@tmmu.edu.cn.
  • 3 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: zhangzihao@tmmu.edu.cn.
  • 4 Department of Gynaecology and Obstetrics, 958 Hospital of PLA Army, Chongqing, 400038, China. Electronic address: chenyin@tmmu.edu.cn.
  • 5 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: chennaicheng@tmmu.edu.cn.
  • 6 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: chenfang@tmmu.edu.cn.
  • 7 Department of Hematology, Daping Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: qiyan@tmmu.edu.cn.
  • 8 Department of Hematology, Daping Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: hanchanghao@tmmu.edu.cn.
  • 9 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: xuyang@tmmu.edu.cn.
  • 10 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: chenmo@tmmu.edu.cn.
  • 11 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: shenmingqiang@tmmu.edu.cn.
  • 12 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: gunny1981@126.com.
  • 13 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: zenghao@tmmu.edu.cn.
  • 14 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: suyongping@tmmu.edu.cn.
  • 15 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China; Chinese PLA Center for Disease Control and Prevention, No. 20 Dongda Street, Fengtai District, Beijing, 100071, China. Electronic address: weichen1111@yahoo.com.
  • 16 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address: wangjunping@tmmu.edu.cn.
PMID: 37075826 DOI: 10.1016/j.yexcr.2023.113603
Abstract

Hematopoietic toxicity due to ionizing radiation (IR) is a leading cause of death in nuclear incidents, occupational hazards, and Cancer therapy. Oxymatrine (OM), an extract originating from the root of Sophora flavescens (Kushen), possesses extensive pharmacological properties. In this study, we demonstrate that OM treatment accelerates hematological recovery and increases the survival rate of mice subjected to irradiation. This outcome is accompanied by an increase in functional hematopoietic stem cells (HSCs), resulting in an enhanced hematopoietic reconstitution ability. Mechanistically, we observed significant activation of the MAPK signaling pathway, accelerated cellular proliferation, and decreased cell Apoptosis. Notably, we identified marked increases in the cell cycle transcriptional regulator Cyclin D1 (Ccnd1) and the anti-apoptotic protein BCL2 in HSC after OM treatment. Further investigation revealed that the expression of Ccnd1 transcript and BCL2 levels were reversed upon specific inhibition of ERK1/2 phosphorylation, effectively negating the rescuing effect of OM. Moreover, we determined that targeted inhibition of ERK1/2 activation significantly counteracted the regenerative effect of OM on human HSCs. Taken together, our results suggest a crucial role for OM in hematopoietic reconstitution following IR via MAPK signaling pathway-mediated mechanisms, providing theoretical support for innovative therapeutic applications of OM in addressing IR-induced injuries in humans.

Keywords

Hematopoietic stem cells; Ionizing radiation; MAPK phosphorylation; Oxymatrine.

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