BACKGROUND

Regulatory T cells (Tregs) are living drugs with feasibility, tolerability, and therapeutic benefits. Although Tregs are linked to asthma prognosis through inflammation regulation, no therapeutic agents specifically designed to manage asthma by upregulating Tregs have been developed to date.

METHODS

We screened a library of 250 natural products using a cytometric bead array. Among the selected candidates, gRb1 was identified for further investigation. The effects of gRb1 on Treg and Th17 populations were evaluated in mouse asthma models and human PBMCs from both healthy donors and asthma patients using flow cytometry and cytokine analysis.

RESULTS

In inflammatory conditions, ginsenoside Rb1 (gRb1, a major ginseng component) increased IL-10- and TGF-β-expressing Treg populations and decreased the Th17 population; activated phospho-STAT5 and NFAT1 in Tregs; inhibited NFAT1 activation in conventional T cells (Tconvs); increased Treg proliferation and Tconv-Treg differentiation, inhibiting Tconv proliferation; and reduced inflammatory cytokine secretion by Tconvs. In asthma model mice, suppression of asthma symptoms by gRb1 was associated with elevated Treg and lower Th17, Th1, and Th2 counts. gRb1 treatment of stimulated PBMCs from patients with asthma and healthy donors increased IL-10- and TGF-β-expressing Treg populations and decreased IL-17A-, IL-22-, IFN-γ-, and TNF-α-expressing T-cell populations.

CONCLUSIONS

gRb1 alleviate asthma by shifting the Treg-inflammatory T cell balance. These findings suggest a strategy for enhancing Treg activity through treatment with gRb1. This may provide a novel therapeutic approach for asthma and related disorders.