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

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.