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

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:

• Salidroside
• Th17/Treg balance
• STAT3/HIF-1α/RORγt pathway
• aplastic anemia

Acknowledgements

The authors would like to thank Editage for the language editing provided for this manuscript. Author contributions: Zenghui Liu and Yang Xiao were mainly responsible for project design, completion, article writing, and the acquisition of financial support. Ling Ouyang, Yu Zhan, and Xuekui Gu were mainly responsible for clinical patient enrollment. Wancheng Chen and Lixuan Chen mainly assisted in the completion of experiments, and proofread the article. Defang Xiong was responsible for obtaining and analyzing the pathological sections and images of mice. Bone marrow cell smears and images were obtained and analyzed by Jiduo Liu. Gao Tianqi was responsible for proofreading, formatting, and submission of the article. Xiaozhen Li and Yanqun Zhou assisted in the completion of cell and animal experiments. Ziyuan Lu mainly assisted in letter reply and ELISA testing of supplementary experiments. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Submission declaration

We declare that its publication has been approved by all the authors.

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Additional information

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).