Abstract
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-κB, 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/Ionomycin 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-κB 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 downregulated together with decreased production of pro-inflammatory cytokines of IL-6, TNF-α and IFN-γ. These results indicate that the NF-κB, 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.
Original language | English |
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Pages (from-to) | 303-315 |
Number of pages | 13 |
Journal | Journal of Cellular Biochemistry |
Volume | 107 |
Issue number | 2 |
DOIs | |
Publication status | Published - 15 May 2009 |
Scopus Subject Areas
- Biochemistry
- Molecular Biology
- Cell Biology
User-Defined Keywords
- AP-1
- NF-κB
- NF-AT
- Saikosaponin-D
- T lymphocyte activation