한국약용작물학회지 (Korean Journal of Medicinal Crop Science)

  • 제15권5호
  • /
  • Pages.311-314
  • /
  • 2007
  • /
  • 1225-9306(pISSN)
  • /
  • 2288-0186(eISSN)
한국약용작물학회 (The Korean Society of Medicinal Crop Science)
권호 표지

Inhibitory Effects of Rehmannia glutinosa Liboschitz on Endothelial Cell Proliferation

  • Lee, Sung-Jin (Gyeong-gi Regional Research Center, Hankyong National University) ;
  • Lee, Hak-Kyo (Gyeong-gi Regional Research Center, Hankyong National University)
  • 발행 : 2007.10.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important angiogenic molecules associated with tumor-induced neovascularization. This study was carried out to investigate inhibitory effect of extracts from root of Rehmannia glutinosa LIBOSCHITZ (Rehmannia Radix and Rehmannia Radix Preparata) on endothelial cell proliferation. The methanol extracts from the medicinal herb were fractionated into n-hexane, ethyl acetate, n-butanol and aqueous fractions. Among the four fractions, the n-butanol fraction from R. Radix on exhibited highly effective inhibition (${\approx}79%$ inhibition) on the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and then ethyl acetate fraction from R. Radix (${\approx}45%$ inhibition) at the concentration of $100\;{\mu}g/ml$. The n-butanol fraction efficiently blocked the VEGF- and bFGF-induced HUVEC proliferation in a dose-dependent manner, but did not affect the growth of HT1080 human fibrosarcoma cells. The n-butanol fraction more efficiently blocked the binding of KDR/Flk-1-Fc to immobilized $VEGF_{165}$ and VEGF- and bFGF-induced human umbilical vein endothelial cell proliferation than the fraction from R. Radix Preparata. Our results suggest that Rehmannia Radix may be used as a candidate for developing anti-angiogenic agent.

키워드

참고문헌

  1. Boehm-Viswanathan T (2000) Is angiogenesis inhibition the Holy Grail of cancer therapy? Curr. Opin. Oncol. 12:89-94 https://doi.org/10.1097/00001622-200001000-00015
  2. Cho SI (2003) Anti-oxidative effects of Rehmannia Radix Preparata on toxic agent induced kidney cell injury. Kor. J. Herbology 18:119-126
  3. De Vries C J, Escobedo A, Ueno H, Houck K, Ferrara N, Wil­liams LT (1992) The fins-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989-991 https://doi.org/10.1126/science.1312256
  4. Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442-447 https://doi.org/10.1126/science.2432664
  5. Folkman J (1991) What is the evidence that tumors are angio­genesis-dependent? J. Natl. Cancer lnst. 82:4-6
  6. Khatri JJ, Johnson C, Magid R, Lessner SM, Laude KM, Dikalov SI, Harrison DG, Sung HJ, Rong Y, Galis ZS (2004) Vascular oxidant stress enhances progression and angio­genesis of experimental atheroma. Circulation, 109:520-525 https://doi.org/10.1161/01.CIR.0000109698.70638.2B
  7. Kim HM, An CS, Jung KY, Cboo YK, Park JK, Nam SY (1999) Rehmannia glutinosa inhibits tumour necrosis factor­alpha and interleukin-1 secretion from mouse astrocytes. Pharmacol Res. 40:171-176 https://doi.org/10.1006/phrs.1999.0504
  8. Kim SS, Son YO, Chun JC, Kim SE, Chung GH, Hwang KJ, Lee JC (2005) Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glu­tinosa. Redox Rep. 10(6):311-8 https://doi.org/10.1179/135100005X83734
  9. Kim YM, Hwang S, Kim YM, Pyun BJ, Kim TY, Lee ST, Gho YS, Kwon YG (2002) Endostatin blocks vascular endothelial growth factor-mediated signaling via direct inter­action with KDR/Flk-1, J. Biol. Chem. 277:27872-27879 https://doi.org/10.1074/jbc.M202771200
  10. Leibovich SJ, Polverini PJ, Fong TW, Harlow LA, Koch A E (1994) Production of angiogenic activity by human mono­cytes requires an L-arginine/nitric oxide-synthase-dependent effector mechanism. Proc. Natl. Acad. Sci. USA. 91:4190­-4194
  11. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Frrarara N (1989) Vascular endothelial growth factor is a secreted angio­genic mitogen, Science 246: 1306-1309 https://doi.org/10.1126/science.2479986
  12. Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator ofvasculogenesis and angiogenesis. Cell 72: 835-846 https://doi.org/10.1016/0092-8674(93)90573-9
  13. Montesano R, Vassalli JD, Baird A, Guillemin Rand Orci L (1986) Basic fibroblast growth factor induces angiogenesis in vitro. Proc. Natl. Acad. Sci. USA. 83:7297-7301
  14. Ncosia RF, Tchao R, Leighton J (1983) Angiogenesis-depen­dent tumor spread in reinforced fibrin clot culture. Cancer Res. 43:2159-2166
  15. Risau W (1990) Angiogenic growth factors. Prog. Growth Fac­tor Res. 2:71-79 https://doi.org/10.1016/0955-2235(90)90010-H
  16. Thomas KA (1987) Fibroblast growth factors. FASEB. 1:434-440 https://doi.org/10.1096/fasebj.1.6.3315806
  17. Tian YY, An LJ, Jiang L, Duan YL, Chen J, Jiang B (2006) Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures. Life Sci. 23(80):193-9
  18. Tomoda M, Miyamoto H, Shimizu N, Gonda R, Obara N (1994) Characterization oftwo polysaccharides having activ­ity on the reticuloendothelial system from the root of Reh­mannia glutinosa. Chem Pharm Bull (Tokyo) 42:625-62 https://doi.org/10.1248/cpb.42.625
  19. Veikkola, T. Alitalo, K. (1999) VEGFs, receptors and angiogen­esis, Semin. Cancer Biol. 9:211-220
  20. Vlodavsky I, Folkman J, Sullivan R, Fridman R, Ishai­Micbaelli R, Sasse J, Klagsbrun M (1987) Endothelial cell­derived basic fibroblast growth factor: synthesis and deposi­tion into subendothelial extracellular matrix. Proc. Natl. Acad. Sci. USA. 84:2292-2296
  21. Wei XL, Ru XB (1997) Effects of low-molecular-weight Reh­mannia glutinosa polysaccharides on p53 gene expression. Zhongguo Yaoli Xuebao 18:471-474
  22. Ziche M, Morbidelli L, Masini E, Amerini S, Granger HJ, Maggi CA, Geppetti P, Ledda F (1994) Nitric oxide medi­ates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J. Clin. Invest. 94:2036-2044 https://doi.org/10.1172/JCI117557