Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis.
In the present study, we aimed at examining the immunosuppressive activity of saikosaponin a, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), and the underlying mechanisms. Saikosaponin a significantly inhibited the proliferation and activation of T cells activated by concanavalin A (Con A) in a concentration-dependent manner. Additionally, it potently suppressed Con A-stimulated IL-2, IFN-gamma and TNF-alpha production in mouse T cells. Saikosaponin a also caused G0/G1 arrest of activated T cells through down-regulating the protein levels of CDK6 and Cyclin D3 and up-regulating the protein level of p27(kip). Furthermore, the compound dose-dependently induced apoptosis of Con A-activated T cells rather than those non-activated, as determined by Annexin V/PI staining. Besides, it induced a remarkable collapse of mitochondrial membrane potential and caused significant release of cytochrome c from mitochondria to cytosol. In summary, these results suggest that the G0/G1 arrest as well as the induction of apoptosis via mitochondrial pathway are involved in the immunosuppressive activity of saikosaponin a against activated T cells. This may herald a novel approach for further studies of saikosaponin a as a candidate for the treatment of inflammatory and autoimmune diseases.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Yang
Y
Sun
Tian-Tian
TT
Cai
Xiao-Bin
XB
Zhou
Qiang
Q
Xu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy; D029972:Bupleurum; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D056743:Cyclin D3; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
C534697:Ccnd3 protein, mouse; C493961:Cdkn1b protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D007376:Interleukin-2; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009828:Oleanolic Acid; D007371:Interferon-gamma; D045304:Cytochromes c; D051361:Cyclin-Dependent Kinase 6; C025759:saikosaponin D