Mechanistic Study of Saikosaponin-d (Ssd) on Suppression of Murine T Lymphocyte Activation

Saikosaponin-d (Ssd) is a triterpene saponin derived from the medicinal plant, Bupleurum falcatum L. (Umbelliferae). Previous findings showed that Ssd exhibits a variety of pharmacological and immunomodulatory activities including anti-inflammatory, anti-bacterial, antiviral and anti-cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF-kappa B, NF-AT and AP-1 signaling pathways, cytokine secretion, and IL-2 receptor expression. The results demonstrated that Ssd not only suppressed OKT3/CD28-costimulated human T cell proliferation, it also inhibited PMA, PMA/lonomycin and Con A-induced mouse T cell activation in vitro. The inhibitory effect of Ssd on PMA-induced T cell activation was associated with down-regulation of NF-kappa B signaling through suppression of IKK and Akt activities. In addition, Ssd suppressed both DNA binding activity and the nuclear translocation of NF-AT and activator protein 1 (AP-1) of the PMA/Ionomycin-stimulated T cells. The cell surface markers like IL-2 receptor (CD25) were also down-regulated together with decreased production of pro-inflammatory cytokines of IL-6, TNF-alpha and IFN-gamma. These results indicate that the NF-kappa B, NF-AT and AP-1 (c-Fos) signaling pathways are involved in the T cell inhibition evoked by Ssd, so it can be a potential candidate for further study in treating T cell-mediated autoimmune conditions. J. Cell. Biochem. 107: 303-315, 2009. (C) 2009 Wiley-Liss, Inc.