The herbal decoction modified Danggui Buxue Tang attenuates immune-mediated bone marrow failure by regulating the differentiation of T lymphocytes in an immune-induced aplastic anemia mouse model

PLoS One. 2017 Jul 6;12(7):e0180417. doi: 10.1371/journal.pone.0180417. eCollection 2017.

Abstract

Angelicae Sinensis, Radix Astragali and Rhizoma Coptidis are all herbs of modified Danggui Buxue Tang (DGBX) and are extensively applied herbs in traditional Chinese medicine for the treatment of anemia and inflammation. In this study, immune-induced AA mice were used as an animal model, and the immunosuppressive agent, Ciclosporin A (CsA), was used as a positive control. Multiple pro-inflammatory cytokines were examined by bead-based multiplex flow cytometry. The T-cell subsets were assessed using a fluorescence-activated cell sorter (FACS). Western blot analysis was used to estimate the protein expression levels of specific transcription factors for T helper cells (Th1, Th2 and Th17) and key molecules of the Janus-activated kinase (Jak)/signal transducer and activator of transcription (Stat3) signaling pathway. DGBX treatment could significantly increase the production of whole blood cells in peripheral blood (PB); inhibit the expansion of Th1 and Th17 cells; increase the differentiation of Th2 and Tregs cells; regulate the expression levels of T-bet, GATA-3, RORγ and proinflammatory cytokines; and decrease the expression levels of key molecules in the Jak/Stat signaling pathway. These results indicate that DGBX can regulate the differentiation of T lymphocytes, resulting in immunosuppressive and hematogenic functions on AA mice. DGBX might be a good candidate for inclusion in a randomized study for AA with more data on the possible side effects and doses used in humans. Ultimately, it may be used for applications of traditional medicine against AA in modern complementary and alternative immunosuppressive therapeutics.

MeSH terms

  • Anemia, Aplastic / drug therapy*
  • Anemia, Aplastic / genetics
  • Anemia, Aplastic / immunology
  • Anemia, Aplastic / pathology
  • Angelica sinensis / chemistry
  • Animals
  • Astragalus propinquus
  • Bone Marrow / drug effects*
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Cell Differentiation / drug effects
  • Cyclosporine / pharmacology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Ranunculaceae / chemistry
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / pathology
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology
  • Th2 Cells / pathology

Substances

  • Drugs, Chinese Herbal
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Immunosuppressive Agents
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • danggui buxue decoction
  • Cyclosporine
  • Huang Qi

Grants and funding

This work was supported by National Natural Science Foundation of China 81373583 (http://www.nsfc.gov.cn/), Fundamental Research Funds for Beijing University of Chinese medicine 2015-JYB -XJQ002 (http://www.bucm.edu.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.