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Anti-angiogenic effect of triterpenoidal saponins from Polygala senega

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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 IC50 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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Acknowledgments

The authors thank Koshiro Company Ltd. for kindly providing the Polygala senega. The authors are grateful to the Hoh-ansha Foundation and the Uehara Memorial Foundation for the financial support. This study was also financially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Masayoshi Arai, Asami Hayashi, Mari Sobou, Shunsuke Ishida, Takashi Kawachi, Naoyuki Kotoku & Motomasa Kobayashi

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  1. Masayoshi Arai
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  2. Asami Hayashi
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  3. Mari Sobou
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  4. Shunsuke Ishida
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  5. Takashi Kawachi
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  6. Naoyuki Kotoku
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  7. Motomasa Kobayashi
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Corresponding author

Correspondence to Motomasa Kobayashi.

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M. Arai and A. Hayashi contributed equally to this work.

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Arai, M., Hayashi, A., Sobou, M. et al. Anti-angiogenic effect of triterpenoidal saponins from Polygala senega . J Nat Med 65, 149–156 (2011). https://doi.org/10.1007/s11418-010-0477-7

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  • DOI: https://doi.org/10.1007/s11418-010-0477-7

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