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, anti-viral and anti-cancer effects. In the current study we have investigated the effects of Ssd on activated mouse T lymphocytes through the NF-kappaB, 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-kappaB 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-kappaB, 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.
Wong
Vincent Kam Wai
VK
Hong Kong Baptist University, Kowloon, Hong Kong.
Zhou
Hua
H
Cheung
Simon Shiu Fai
SS
Li
Ting
T
Liu
Liang
L
D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D012503:Saponins; D018808:Transcription Factor AP-1; D009828:Oleanolic Acid; C025759:saikosaponin D