Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (5): 1218-1229.DOI: 10.19852/j.cnki.jtcm.20260514.001

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Integrative network pharmacology and experimental validation to decipher the anti-angiogenic mechanisms of Xuandan Sanjie decotion (玄丹散结汤) in adenomyosis

GAN Lin1,2, ZHOU Fangfang1, QIU Yingying3, HUANG Meihua1, LI Zhenli1(), GUI Tao1()   

  1. 1 Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
    2 Department of Gynecology, Affiliated Jiangning Hospital of Chinese Medicine, China Pharmaceutical University, Nanjing 211100, China
    3 Department of Gynecology, Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou 221112, China
  • Received:2025-05-22 Accepted:2026-02-09 Online:2026-10-15 Published:2026-05-14
  • Contact: GUI Tao, Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China. guitao@jsatcm.com; LI Zhenli, Department of Obstetrics and Gynecology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China. lizhenli79@163.com,Telephone: +86-25-85630285
  • About author:

    GAN Lin and ZHOU Fangfang are co-first authors and contributed equally to this work

  • Supported by:
    National Natural Science Foundation of China: To Explore the Effect and Mechanism of Yiqi Sanjie Decoction in Relieving Pain of Adenomyosis Based on the Nerve Growth Factor/Extracellular Regulated Protein Kinases pathway(81403321);Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine: Study on the Mechanism of Xuandan Sanjie Decoction Regulating the Estradiol/G-protein Coupled Estrogen Receptor 1 /Hypoxia Inducible Factor-1α Pathway of Endometrial Mesenchymal Stem Cells to Inhibit Angiogenesis in Uterine Adenomyosis(MS2023039);Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine: Study on the Mechanism of the Formula of Tonifying Kidney and Activating Blood Circulation and Dissipating Blood Stasis in Regulating Macrophage Polarization and Improving Endometrial Receptivity Based on the miRNA-103a-3p/Dual Specificity Protein Phosphatase 2/Extracellular Regulated Protein Kinases Axis(MS2023079);Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine: Based on the Study of Inducing Macrophage Polarization by Endometrial Mesenchymal Stem Cells, Exploring the Mechanism of the "Supplement Kidney and Activate Blood, Dispel Stasis" Formula in Inhibiting the Invasion and Migration of Endometrium in Uterine Adenomyosis(ZD202419);Nanjing Jiangning District Science and Technology Benefit People Plan Project: In vitro Mechanism of Xuandan Sanjie Decoction Inhibiting Adenomyosis Angiogenesis through the Estradiol/Hypoxia Inducible Factor-1α Pathway(2024003S);Jiangsu Chinese Medicine Society: Mechanistic Study of Xuandan Sanjie Decoction in the Treatment of Adenomyosis via Inhibiting Transferrin Receptor Protein 1-mediated Ferroptosis(CYTF2024025);Research Project Funding from Affiliated Jiangning Hospital of Chinese Medicine, China Pharmaceutical University: Xuandan Sanjie Decoction Suppresses Adenomyosis by Modulating Ferroptosis through Transferrin Receptor/Nuclear Receptor Coactivator 4-mediated Ferritinophagy(YJZD2025001);Science and Technology Program of Xuzhou: Research and Development of Intervention Technology for Embryo Implantation Disorders in Adenomyosis Based on a 3D Endometrium-Embryo Co-culture Platform(KC25074)

Abstract:

OBJECTIVE: To investigate the mechanisms by which Xuandan Sanjie decoction (玄丹散结汤, XSD) inhibits angiogenesis in adenomyosis (AM), using both AM-derived primary endometrial stromal cells (ESCs) and a mouse model.

METHODS: Core components and targets of XSD for AM treatment were predicted using multiple databases. Gene ontology and kyoto encyclopedia of genes and genomes pathway analyses were used to elucidate the potential mechanisms. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was applied to identify chemical constituents of XSD. A cobalt (II) chloride (CoCl2)-induced hypoxia-mimicking ESC model and an AM mouse model were established to experimentally validate the anti-angiogenic effects of XSD.

RESULTS: According to bioinformatics analysis, hypoxia signaling and angiogenesis are crucial for AM progression. Twenty chemical constituents of the 106 compounds identified from the Traditional Chinese Medicine systems pharmacology database and analysis platform database were validated by UHPLC-MS/MS. Network pharmacology identified protein kinase B alpha, epidermal growth factor receptor, hypoxia inducible factor-1α (HIF-1α), and estrogen receptor 1 (ESR1) as core targets. According to in vitro and in vivo experiments, XSD exhibits anti-angiogenic properties through ESR1/G protein-coupled estrogen receptor (GPER)-mediated HIF-1α signaling.

CONCLUSION: Our study confirms that XSD inhibits angiogenesis in AM viaESR1/GPER-mediated HIF-1α signaling. These findings elucidate the molecular mechanisms underlying XSD's therapeutic effects for abnormal uterine bleeding associated with adenomyosis, offering new therapeutic strategies for this condition.

Key words: network pharmacology, endometrial stromal cells, adenomyosis, angiogenesis, Xuandan Sanjie decoction

Cite this article

GAN Lin, ZHOU Fangfang, QIU Yingying, HUANG Meihua, LI Zhenli, GUI Tao. Integrative network pharmacology and experimental validation to decipher the anti-angiogenic mechanisms of Xuandan Sanjie decotion (玄丹散结汤) in adenomyosis[J]. Journal of Traditional Chinese Medicine, 2026, 46(5): 1218-1229.