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Journal of Traditional Chinese Medicine >

2025 , Vol. 45 >Issue 5: 1087 - 1097

DOI: https://doi.org/10.19852/j.cnki.jtcm.2025.05.015

Original Articles

Therapeutic potential of Traditional Chinese Medicine Yisui Shengxue pills (益髓生血丸) to inhibit hypoxia-inducible factor-1alpha and general control nonderepressible 2 to regulate the post-chemotherapy immune response: integrating network pharmacology and experimental validation

  • Yafeng QI ,
  • Yu LIU ,
  • Yeyuan LIU ,
  • Yangyang LI ,
  • Shangzu ZHANG ,
  • Yaping CHEN ,
  • Qian XU ,
  • Guoxiong HAO ,
  • Yongqi LIU ,
  • Liying ZHANG ,
  • Zhiming ZHANG
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  • 1 Clinical School of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
    2 School of Integrative Chinese and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
    3 School of Basic Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
    4 Department of Oncology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China

Received date: 2024-08-22

  Accepted date: 2024-12-25

  Online published: 2025-09-15

Supported by

High-end Talents Undertake Provincial Science and Technology Plan Projects(Yangtze River Scholars Award Scheme; Gankeji 2021: reference 20-9);Gansu Province Integrated Traditional Chinese and Western Medicine Tumor Clinical Medical Research Center(Reference: 18JR2FA001)

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Abstract

OBJECTIVE: To investigate the efficacy and mechanism of Traditional Chinese Medicine Yishui Shengxue pills (益髓生血丸, YSSX) in mouse models of immunosuppression induced by three chemotherapy drugs.

METHODS: We determined an optimal intervention dose of YSSX to investigate efficacy. Changes in immune cell subpopulations were detected by flow cytometry, while immunofluorescence, immunohistochemistry, and other molecular biology methods, were used to verify pathway targets. We used PX-478, an inhibitor of hypoxia-inducible factor-1α (HIF-1α), to validate the mechanism of action.

RESULTS: Analysis showed that YSSX enhanced the immunity of mouse models of immunosuppression. At the cellular level, YSSX reduced the numbers of myeloid-derived suppressor cells (MDSCs) and enhanced CD8+ T cell infiltration. At the molecular level, YSSX reduced the expression levels of hypoxia-inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), general control nonderepressible 2 (GCN2), and eukaryotic initiation factor 2α (eIF2α) in mouse MDSCs, thereby reducing the transcription of HIF-1α, GCN2, and eIF2α mRNA. Collectively, these changes led to the increased secretion of interferon-γ and interleukin 12, concomitant with a reduction in tumor necrosis factor-α level.

CONCLUSIONS: YSSX improved MDSC-mediated immunosuppression in a mouse model after chemotherapy by inhibiting the HIF-1α/iNOS-GCN2/eIF2α signaling axis.

Key words： drug therapy; immunosuppression therapy; myeloid-derived suppressor cells; post-chemotherapy; network pharmacology; Yishui Shengxue pills

Cite this article

Yafeng QI , Yu LIU , Yeyuan LIU , Yangyang LI , Shangzu ZHANG , Yaping CHEN , Qian XU , Guoxiong HAO , Yongqi LIU , Liying ZHANG , Zhiming ZHANG . Therapeutic potential of Traditional Chinese Medicine Yisui Shengxue pills (益髓生血丸) to inhibit hypoxia-inducible factor-1alpha and general control nonderepressible 2 to regulate the post-chemotherapy immune response: integrating network pharmacology and experimental validation[J]. Journal of Traditional Chinese Medicine, 2025 , 45(5) : 1087 -1097 . DOI: 10.19852/j.cnki.jtcm.2025.05.015

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