Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis
Saikosaponin a inhibits the proliferation and activation of T cells through cell cycle arrest and induction of apoptosis
复制标题
Saikosaponin a 通过细胞周期停滞和诱导细胞凋亡来抑制 T 细胞的增殖和活化。
DOI：
10.1016/j.intimp.2009.04.006
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发表时间：
2009-07-01
影响因子：
5.6
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Sun, Yang;Cai, Tian-Tian;Xu, Qiang
本研究旨在研究柴胡皂苷a的免疫抑制活性及其机制。柴胡皂苷a是一种从伞形科柴胡中提取的三萜皂苷。柴草皂苷a显著抑制刀豆蛋白a （cona）激活的T细胞的增殖和活化，并呈浓度依赖性。此外，它还能有效抑制Con a刺激的小鼠T细胞中IL-2、ifn - γ和tnf - α的产生。Saikosaponin a还通过下调CDK6和Cyclin D3蛋白水平，上调p27（kip）蛋白水平，导致活化T细胞G0/G1阻滞。此外，通过Annexin V/PI染色，化合物剂量依赖性地诱导Con a激活的T细胞凋亡，而不是非激活的T细胞。此外，它还诱导了线粒体膜电位的显著崩溃，并引起细胞色素c从线粒体向胞质溶胶的大量释放。综上所述，这些结果表明，G0/G1阻滞以及通过线粒体途径诱导细胞凋亡参与了柴草皂苷a对活化T细胞的免疫抑制活性。这可能预示着柴草皂苷a作为治疗炎症和自身免疫性疾病的候选药物的进一步研究的新途径。(C) 2009 Elsevier B.V.版权所有
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. (C) 2009 Elsevier B.V. All rights reserved.