Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology
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Autoimmune Diseases / drug therapy
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Bupleurum*
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Cell Cycle / drug effects
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Cell Cycle / immunology
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Cell Proliferation / drug effects
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Cyclin D3
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Cyclin-Dependent Kinase 6 / genetics
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Cyclin-Dependent Kinase 6 / immunology
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Cyclin-Dependent Kinase 6 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / immunology
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Cyclins / genetics
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Cyclins / immunology
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Cyclins / metabolism*
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Cytochromes c / metabolism
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Dose-Response Relationship, Drug
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Down-Regulation
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Female
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Immunosuppression Therapy
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / immunology
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Mice
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Mice, Inbred BALB C
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Oleanolic Acid / analogs & derivatives*
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Oleanolic Acid / pharmacology
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Saponins / pharmacology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation
Substances
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Ccnd3 protein, mouse
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Cdkn1b protein, mouse
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Cyclin D3
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Cyclins
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Interleukin-2
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Saponins
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Tumor Necrosis Factor-alpha
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Cyclin-Dependent Kinase Inhibitor p27
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Oleanolic Acid
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Interferon-gamma
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Cytochromes c
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Cyclin-Dependent Kinase 6
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saikosaponin D