An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial

  1. Caigang Liu  Is a corresponding author
  2. Hong Yu
  3. Guanglei Chen
  4. Qichao Yang
  5. Zichu Wang
  6. Nan Niu
  7. Ling Han
  8. Dongyu Zhao
  9. Manji Wang
  10. Yuanyuan Liu
  11. Yongliang Yang  Is a corresponding author
  1. Shengjing Hospital of China Medical University, China
  2. Dalian University of Technology, China
  3. China Resources Sanjiu Medical and Pharmaceutical Co, Ltd, China
  4. Peking University, China
  5. Shanghai BeautMed Corporation, China
  6. University of Copenhagen, Denmark

Abstract

Background: Plasma cell mastitis (PCM) is a nonbacterial breast inflammation with severe and intense clinical manifestation yet treatment methods for PCM are still rather limited. Although the mechanism of PCM remains unclear, mounting evidences suggest that the dysregulation of immune system is closely associated with the pathogenesis of PCM. Drug combinations or combination therapy could exert improved efficacy and reduced toxicity through hitting multiple discrete cellular targets.

Methods: We have developed a knowledge graph architecture towards immunotherapy and systematic immunity that consists of herbal drug-target interactions with a novel scoring system to select drug combinations based on target-hitting rates and phenotype relativeness. To this end, we employed this knowledge graph to identify an herbal drug combination for PCM and we subsequently evaluated the efficacy of the herbal drug combination in clinical trial.

Results: Our clinical data suggests that the herbal drug combination could significantly reduce the serum level of various inflammatory cytokines, downregulate serum IgA and IgG level, reduce the recurrence rate and reverse the clinical symptoms of PCM patients with improvements of general health status.

Conclusions: In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of plasma cell mastitis patients. We demonstrated that the herbal drug combination holds great promise as an effective remedy for PCM, acting through the regulation of immunoinflammatory pathways and improvement of systematic immune level. In particular, the herbal drug combination could significantly reduce the recurrence rate of PCM, a major obstacle for PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.

Funding: Liu's lab was supported by grants from the Public Health Science and Technology Project of Shenyang (Grant: 22-321-32-18), Y. Yang's laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301); the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (2021JH1/10400050).

Clinical trial number: ClinicalTrials.gov: NCT05530226.

Data availability

Figure 1-3 are computational study and therefore no data have been generated for the manuscript. In addition, Figure 4 - Source Data, Figure 5 - Source Data, Figure 6 - Source Data 1, Figure 6 - Source Data 2 and Figure 6 - Source Data 3 contain the numerical data used to generate the figures have been included in the manuscript.

Article and author information

Author details

  1. Caigang Liu

    Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
    For correspondence
    angel-s205@163.com
    Competing interests
    Caigang Liu, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2083-235X
  2. Hong Yu

    Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
    Competing interests
    No competing interests declared.
  3. Guanglei Chen

    Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
    Competing interests
    No competing interests declared.
  4. Qichao Yang

    School of Bioengineering, Dalian University of Technology, Dalian, China
    Competing interests
    No competing interests declared.
  5. Zichu Wang

    School of Bioengineering, Dalian University of Technology, Dalian, China
    Competing interests
    No competing interests declared.
  6. Nan Niu

    Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
    Competing interests
    No competing interests declared.
  7. Ling Han

    China Resources Sanjiu Medical and Pharmaceutical Co, Ltd, Shenzhen, China
    Competing interests
    Ling Han, is an employee of China Resources Sanjiu Medical & Pharmaceutical..
  8. Dongyu Zhao

    International Cancer Institute, Peking University, Beijing, China
    Competing interests
    No competing interests declared.
  9. Manji Wang

    Shanghai BeautMed Corporation, Shanghai, China
    Competing interests
    Manji Wang, is an employee of Shanghai BeautMed Corporation..
  10. Yuanyuan Liu

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    No competing interests declared.
  11. Yongliang Yang

    School of Bioengineering, Dalian University of Technology, Dalian, China
    For correspondence
    everbright99@foxmail.com
    Competing interests
    Yongliang Yang, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0449-0599

Funding

National Natural Science Foundation of China (81874301)

  • Yongliang Yang

National Natural Science Foundation of China (81572609)

  • Caigang Liu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jameel Iqbal, DaVita Labs, United States

Ethics

Human subjects: The protocol was approved by the Institutional Review Board (IRB) of the China Medical University (approval number: 2021PS024T). This study was registered with ClinicalTrials.gov: NCT05530226. All patients provided written informed consent.

Version history

  1. Received: October 24, 2022
  2. Preprint posted: December 6, 2022 (view preprint)
  3. Accepted: March 8, 2023
  4. Accepted Manuscript published: March 14, 2023 (version 1)
  5. Accepted Manuscript updated: March 15, 2023 (version 2)
  6. Version of Record published: March 30, 2023 (version 3)

Copyright

© 2023, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Caigang Liu
  2. Hong Yu
  3. Guanglei Chen
  4. Qichao Yang
  5. Zichu Wang
  6. Nan Niu
  7. Ling Han
  8. Dongyu Zhao
  9. Manji Wang
  10. Yuanyuan Liu
  11. Yongliang Yang
(2023)
An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
eLife 12:e84414.
https://doi.org/10.7554/eLife.84414

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https://doi.org/10.7554/eLife.84414

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