9,19-Cycloartenol glycoside G3 from Cimicifuga simplex regulates immune responses by modulating Th17/Treg ratio

Cimicifuga simplex is a medicinal herb which has a wide range of biological activities. We isolated seven 9,19-cycloartenol glycosides from the roots of C. simplex, and among the glycosides, G3 exhibited the strongest inhibitory effect on immune responses, including suppressing the differentiation of CD⁴⁺ T cells and directly suppressing the cytokine-induced JAK/STAT signaling pathways. In the IL-23-induced mouse ear model of skin disease, G3 repressed disease development by inhibiting the expression of pro-inflammatory mediators in murine ear skin. Moreover, G3 affected the maturation of DCs in vitro, thereby inducing T cell differentiation, resulting in an increased Treg phenotype and decreased Th17 phenotype. This study provides new evidence that G3 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD⁴⁺ T cell differentiation and the IL-17⁺RORγt⁺/IL-10⁺FoxP3⁺ ratio. These findings suggest that G3 might mediate the therapeutic effects observed in psoriasis patients following treatment with C. simplex.