Anti-angiogenic effect of triterpenoidal saponins from Polygala senega
Anti-angiogenic effect of triterpenoidal saponins from Polygala senega
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DOI：
10.1007/s11418-010-0477-7
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Kobayashi, Motomasa
中科院分区：
文献类型：
--
作者：
Arai, Masayoshi;Hayashi, Asami;Kobayashi, Motomasa
远志皂苷[senegin II（1），senegin III（2），senegin IV（3），senegasaponin a（4），senegasaponin B（5）]被重新发现为抗人脐静脉内皮细胞（HUVEC）增殖的选择性物质。Senegasaponins（1-5）对HUVEC显示出抗增殖活性，IC 50值在0.6-6.2 μ M范围内，并且选择指数是几种癌细胞系的7-100倍，而Senegasaponins（6）和tenuifolin（7）的去酰基混合物失去了抗增殖活性，这表明28-O-糖苷部分和甲氧基肉桂酰基对于Senegasaponins的HUVEC选择性生长抑制是必需的。在小鼠基质胶塞试验中，Senegin III（2）抑制血管内皮生长因子（VEGF）诱导的HUVEC体外肾小管形成和碱性成纤维细胞生长因子（bFGF）诱导的体内新血管形成。此外，senegin III（2）抑制ddY小鼠s.c.接种小鼠肉瘤S180细胞。对senegin III（2）作用机制的分析表明，诱导色素上皮衍生因子（PEDF）参与了senegasaponins的抗血管生成作用。
Senegasaponins [senegin II (1), senegin III (2), senegin IV (3), senegasaponin a (4), and senegasaponin b (5)] from Polygala senega were re-discovered as selective anti-proliferative substances against human umbilical vein endothelial cells (HUVECs). Senegasaponins (1-5) showed anti-proliferative activity against HUVECs with IC50 values in the range 0.6-6.2 mu M, and the selective index was 7-100-fold in comparison with those for several cancer cell lines, while the desacyl mixture of senegasaponins (6) and tenuifolin (7) lost anti-proliferative activity, indicating that the 28-O-glycoside moiety and methoxycinnamoyl group were essential for the HUVEC-selective growth inhibition of senegasaponins. Senegin III (2) inhibited the vascular endothelial growth factor (VEGF)-induced in vitro tubular formation of HUVECs and basic fibroblast growth factor (bFGF)-induced in vivo neovascularization in the mouse Matrigel plug assay. Moreover, senegin III (2) suppressed tumor growth in the ddY mice s.c.-inoculated murine sarcoma S180 cells. The analysis of the action mechanism of senegin III (2) suggested that the induction of pigment epithelium-derived factor (PEDF) would contribute to the anti-angiogenic effects of senegasaponins.