Anti-angiogenic effect of triterpenoidal saponins from Polygala senega.
ABSTRACT 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 IC(50) values in the range 0.6-6.2 μM, 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.
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ABSTRACT: The dried root of Polygala tenuifolia, named Radix Polygalae, is a well-known traditional Chinese medicine. Triterpenoid saponins are some of the most important components of Radix Polygalae extracts and are widely studied because of their valuable pharmacological properties. However, the relationship between gene expression and triterpenoid saponin biosynthesis in P. tenuifolia is unclear.PLoS ONE 08/2014; 9(8):e105765. DOI:10.1371/journal.pone.0105765 · 3.53 Impact Factor
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ABSTRACT: A rapid and specific LC-MS/MS method has been developed for the simultaneous analysis of polygala acid, senegenin and 3,6'-disinapoylsucrose (DSS) in rat plasma. The method was applied to the pharmacokinetics studies of polygala acid, senegenin and DSS. The analysis was carried out on an Agilent Eclipse plus C18 reversed-phase column (100 × 4.6 mm, 3.5 µm) by gradient elution with methanol and ammonia (0.01%, v/v). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polygala acid and DSS ranging from 2.5 to 2000 ng/mL, and senegenin ranging from 5 to 2000 ng/mL. The intra- and inter-day precisions (relative standard deviation) were <11.34 and 8.99%. The extraction recovery ranged from 70.89 ± 4.60 to 88.49 ± 3.26%, and that for the IS was 77.23 ± 3.68%. Stability studies showed that polygala acid, senegenin and DSS are stable during the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of polygala acid, senegenin and DSS. Copyright © 2013 John Wiley & Sons, Ltd.Biomedical Chromatography 05/2014; 28(5). DOI:10.1002/bmc.3076 · 1.95 Impact Factor
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ABSTRACT: Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of dioscin. We showed that dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied with obvious blood vessel decrease within solid tumors. We also found dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF-induced blood vessel formation in vivo. We also identified that dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied with the increase of phosphorylated P38MAPK. The results potently suggest that dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways.Toxicology and Applied Pharmacology 08/2014; DOI:10.1016/j.taap.2014.07.026 · 3.98 Impact Factor