Salidroside affects the Th17/Treg cell balance in aplastic anemia via the STAT3/HIF-1α/RORγt pathway

Redox Rep. 2023 Dec;28(1):2225868. doi: 10.1080/13510002.2023.2225868.

Abstract

Background: Acquired aplastic anemia (AA) is a life-threatening disease associated with an imbalance in Th17/Treg cells. Regulating this balance may be an effective treatment approach for AA. Rhodiola rosea has shown efficacy in AA treatment, but its mechanisms remain unclear.

Purpose: We investigated salidroside's effect (a component of Rhodiola rosea) on Th17/Treg balance in adult AA patients and a mouse model.

Methods: HIF-1α mRNA and protein levels were measured in AA patients' peripheral blood. Flow cytometry, qRT-PCR, and WB analyzed salidroside's impact on T cell differentiation, Th17 cells, Treg cells, STAT3, HIF-1α, and RORγt expression. ELISA measured hematopoietic growth factors in mouse serum.

Results: AA patients exhibited elevated HIF-1α levels. Salidroside improved hematopoietic function, increasing blood cell count and enhancing bone marrow. Salidroside induced SCF, TPO, and IL-3 expression while inhibiting IL-2 in mice. Salidroside reduced STAT3, HIF-1α, RORγt, and IL-17a, while increasing FoxP3 expression, correcting the Th17/Treg imbalance in vitro and in vivo.

Conclusion: Salidroside has potential as a novel AA treatment by correcting the Th17/Treg imbalance through the STAT3/HIF-1α/RORγt pathway.

Keywords: STAT3/HIF-1α/RORγt pathway; Salidroside; Th17/Treg balance; aplastic anemia.

MeSH terms

  • Anemia, Aplastic* / drug therapy
  • Animals
  • Glucosides* / pharmacology
  • Glucosides* / therapeutic use
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • STAT3 Transcription Factor
  • T-Lymphocytes, Regulatory*
  • Th17 Cells

Substances

  • Glucosides
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • rhodioloside
  • STAT3 Transcription Factor
  • Hypoxia-Inducible Factor 1, alpha Subunit

Grants and funding

This work was supported by funding from the National Natural Science Foundation of China (project no. 81903973, project no. 81873426), Guangdong Traditional Chinese Medicine Bureau (project no. 20202064), Youth Research Fund Project of the Innovation to Strengthen Hospital Project of The First Affiliated Hospital of Guangzhou University of Chinese Medicine (project no. 2019QN03) and Science and Technology Innovation Strategy Special Fund of Guangdong Province (project no. 2019A1515010390). Shenzhen Science and Technology Program (project no. JCYJ20220530151613030), Sub-item funding for health science and technology projects under the Nanshan District Technology Research and Creative Design Project, Shenzhen City (project no. NS2022004).