The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
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Study on Antiangiogenic Effect of Black Ginseng Radix

흑삼의 신생혈관 억제활성에 대한 연구

  • Song, Gyu-Yong (College of Pharmacy, Chungnam National University) ;
  • Chung, Kyu-Jin (College of Pharmacy, Chungnam National University) ;
  • Shin, Young-Jin (College of Pharmacy, Chungnam National University) ;
  • Lee, Gye-Won (Department of Pharmaceutical Engineering, Konyang University) ;
  • Lee, Sook-Young (Department of Herbal Resources, Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Seo, Young-Bae (Department of Herbalogy, College of Oriental Medicine, Daejeon University)
  • 송규용 (충남대학교 약학대학 약학과) ;
  • 정규진 (충남대학교 약학대학 약학과) ;
  • 신영진 (충남대학교 약학대학 약학과) ;
  • 이계원 (건양대학교 제약공학과) ;
  • 이숙영 (원광대학교 한의학전문대학원 한약자원개발학과) ;
  • 서영배 (대전대학교 한의과대학 한의학과)
  • Received : 2011.08.15
  • Accepted : 2011.09.17
  • Published : 2011.09.30
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Abstract

Objectives : This study was performed to investigate the influence of black ginseng radix extracts (BG) and ginsenoside Rg3, Rg5 on basic fibroblast growth factor (bFGF) induced proliferation, migration and capillary tubule-like formation of human umbilical vein endothelial cells (HUVECs). Methods : HUVECs were cultured with BG and ginsenoside Rg3, Rg5 at different concentrations (60, 125, 250, 500, $1,000{\mu}g/m\ell$) for 2 day In the presence of bFGF, respectively. XTT was used to detect the proliferation. Migration and tube formations were examined to detect the antiangiogenesis. Also, the chick embryo chorioallantoic membrane (CAM) assay was performed to detect the antiangiogenesis. Results : BG and ginsenoside Rg3, Rg5 significantly inhibited bFGF-induced endothelial cell proliferation and migration in a dose-dependent manner. Tube formation in bFGF-induced HUVECs were suppressed by BG and ginsenoside Rg3, Rg5. Moreover, BG and ginsenoside Rg3, Rg5 (30-$50{\mu}g$/egg) inhibited new blood vessel formation on the growing CAM. Conclusions:Based on the present results, it can be suggested that BG has a potential chemopreventive agent via antiangiogenesis.

Keywords

References

  1. Lee SI. The history of Korean ginseng 2nd. Samhwa press. 1980:166.
  2. Keum YS, Park KK, Lee JM, Chun KS, Park JH, Lee SK, Kwon H, Surh YJ. Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. Cancer Lett. 2000;150:41-48. https://doi.org/10.1016/S0304-3835(99)00369-9
  3. Lee JH, Shen GN, Kim EK, Shin HJ, Myung CS, Oh HJ, Kim DH, Roh SS, Cho W, Seo YB, Park YJ, Kang CW, Song GY. Preparation of black ginseng and its antitumor activity. 2006;20(4):951-956.
  4. Song GY, Ph HJ, Roh SS, Seo YB, Park YJ, Myung CS. Effect of black ginseng on body weight and lipid profiles in male rats fed normal diets. Yakhak Hoeji. 2006;50:381-385.
  5. Kim EK, LEE JH, Cho SH, Shen GN, Jin LG, Myung CS, Oh HJ, Kim DH, Yun JD, Roh SS, Park YJ, Seo YB, Song GY. Preparation of black panax ginseng by new methods and its antitumor activity. The Korea Journal Herbology. 2008;23(1):85-92.
  6. Kim Y. Deoxypodophyllotoxin; the cytotoxic and antiangiogenic component from Pulsatilla koreana. Planta Med. 2003;68(3):271-274.
  7. Griffioen AW, Molema G. Angiogenesis:potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol. Rev. 2000;52(2):237-68.
  8. Bergers G, Benjamin L. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer. 2002;3:401-410.
  9. Folkman J. Angiogenesis and apoptosis. Semin. Cancer Biol. 2003;3:159-167.
  10. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407:249-57. https://doi.org/10.1038/35025220
  11. Folkman J, Siegel Y. Angiogenesis. J Biol Chem. 1992;267:10931-10934.
  12. Boyd D. Invasion and metastasis. Cancer Metastasis Rev. 2006;15(1):77-89.
  13. Nam NH, Kim HM, Bae KH. Ahn BZ. Inhibitory effects of Vietnamese medicinal plants on tubelike formation of human umbilical venous cells. Phytother.Res. 2003;17:107-111. https://doi.org/10.1002/ptr.934
  14. Lee KH, Choi HR. Kim CH. Anti-angiogenic effect of the see extract of Benincasa hipida Cogniaux. J. Ethnophamacol. 2005;97:509-513. https://doi.org/10.1016/j.jep.2004.12.008
  15. Song YS, Kim SH, Sa JH, Jin C, Lim CJ, Park EH. Anti-acngiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus. J. Ethnopharmacol. 2003;88:113-116. https://doi.org/10.1016/S0378-8741(03)00178-8
  16. Kim JS, Park BY, Park EK, Lee HS, Hahm JC, Bae KH, Kim MY. Screening of Anti-angiogenic Activity from Plant Extracts. Korean Journal of Pharmacognosy. 2006;37(4):253-257.
  17. Huh JE, Baek YH, Lee JD, Choi DY, Park DS. Screening and mechanism study of angiogenesis in many herbs medicine. The journal of Korean Acupuncture & Moxibustion Society. 2007;24(5):23-32.
  18. Plate KH, Breier G, Risau W. Molecular mechanisms of developmental and tumor angiogenesis. Brain Pathol. 1994;4:207-18. https://doi.org/10.1111/j.1750-3639.1994.tb00835.x
  19. Ha YW, Lim SS, Ha IJ, Na YC, Seo JJ, Shin H, Son SH, Kim YS. Preparative isolation of four ginsenosides from Korean red ginseng (steam-treated Panax ginseng C. A. Meyer), by high-speed countercurrent chromatography coupled with evaporative light scattering detection. Journal of Chromatography, A. 2007;1151(1):37-44. https://doi.org/10.1016/j.chroma.2007.01.038
  20. Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins.Identification by morphologic and immunologic criteria. J Clin Invest. 1973;52:2745-2756. https://doi.org/10.1172/JCI107470
  21. Jost LM, Kirkwood JM, Whiteside TL. Improved short- and long-term XTT-based colorimetric cellular cytotoxicity assay for melanoma and other tumor cells. J Immunol Methods. 1992;147:153-165. https://doi.org/10.1016/S0022-1759(12)80003-2
  22. Reynolds AR, Reynolds LE, Nagel TE, Lively JC, Robinson SD, Hicklin DJ, Bodary SC, Hodivala-Dilke KM. Elevated Flk1 (Vascular Endothelial Growth Factor Receptor 2) Signaling Mediates Enhanced Angiogenesis in $\beta_{3}$-Integrin-Deficient Mice. Cancer Res. 2004;64:8643-8650. https://doi.org/10.1158/0008-5472.CAN-04-2760
  23. Grant DS, Kinsella JL, Fridman R, Auerbach R, Piasecki BA, Yamada Y, Zain M, Kleinman HK. Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo. J Cell Physiol. 1992;153:614-25. https://doi.org/10.1002/jcp.1041530324
  24. Nguyen HT, Yang SY, Kim JA, Song GY, Kim YH. Dammarane-type saponins from the black ginseng. Bulletin of the Korean Chemical Society. 2010;31(11):3423-3426. https://doi.org/10.5012/bkcs.2010.31.11.3423
  25. Liu L, Zhu XM, Wang QJ, Zhang DL, Fang ZM, Wang CY, Wang Z, Sun BS, Wu H, Sung CK. Enzymatic preparation of 20(S,R)-protopanaxadiol by transformation of 20(S,R)-Rg3 from black ginseng. Phytochemistry. 2010;71(13):1514-1520. https://doi.org/10.1016/j.phytochem.2010.05.007
  26. Sun BS, Gu LJ, Fang ZM, Wang CY, Wang Z, Sung CK. Determination of 11 ginsenosides in black ginseng developed from Panax ginseng by high performance liquid chromatography. Food Science and Biotechnology. 2009;18(2):561-564.
  27. Kim HJ, Lee, JY, You BR, Kim HR, Choi JE, Nam KY et al. Antioxidant activities of ethanol extracts from black ginseng prepared by steaming-drying cycles. J Korean Soc Food Sci Nutr. 2011;40(2):156-162. https://doi.org/10.3746/jkfn.2011.40.2.156
  28. Kim AJ, Kang SJ, Lee KH, Lee MS, Ha SD, Cha YS, Kim SY. The chemopreventive potential and anti-inflammatory activities of Korean black ginseng in colon26-M3.1 carcinoma cells and macrophages. J Korean Soc Appl Biol Chem. 2010;53(1):101-105.
  29. Lee MR, Yun BS, Sun BS, Liu L, Zhang, DL, Wang CY, Wang Z, Ly SY, Mo EK, Sung CK. Change of ginsenoside Rg3 and acetylcholinesterase inhibition of black ginseng manufactured by grape juice soaking. J Gineng Res. 2009;33(4):349-354. https://doi.org/10.5142/JGR.2009.33.4.349
  30. Lee MR, Yun BS, Liu L, Zhang DL, Wang Z, Wang CL, Gu LJ, Wang CY, Mo EK, Sung CK. Effect of black ginseng on memory improvement in the amnesic mice induced by scopolamine. J Ginseng Res. 2010;34(1):51-58. https://doi.org/10.5142/JGR.2010.34.1.051
  31. Folkman J. Tumor angiogenesis:therapeutic implications. N. Engl. J. Med. 1971;285:1182-1186. https://doi.org/10.1056/NEJM197111182852108
  32. Kim LS, MacDonald NJ, Gubich ER. Angiostatin and Endostatin:Endogenous Inhibitors of Tumor Growth. Cancer and metastasis reviews. 2000;19(1):181-190. https://doi.org/10.1023/A:1026551202548
  33. Yue PY, Wong DY, Ha WY, Fung MC, Mak NK, Yeung HW, Leung HW, Chan K, Liu L, Fan TP, Wong RN. Elucidation of the mechanisms underlying the angiogenic effects of ginsenoside Rg(1) in vivo and in vitro. Angiogenesis. 2005;8(3):205-16. https://doi.org/10.1007/s10456-005-9000-2
  34. Yu LC, Chen SC, Chang WC, Huang YC, Lin KM, Lai PH, Sung HW. Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng:in vitro and in vivo studies. Int J Pharm. 2007;328(2):168-76. https://doi.org/10.1016/j.ijpharm.2006.08.009
  35. Yue PY, Wong DY, Wu PK, Leung PY, Mak NK, Yeung HW, Liu L, Cai Z, Jiang ZH, Fan TP, Wong RN. The angiosuppressive effects of 20(R)-ginsenoside Rg3. Biochem Pharmacol. 2006;72(4):437-45. https://doi.org/10.1016/j.bcp.2006.04.034
  36. Chen MW, Ni L, Zhao XG, Niu XY. The inhibition of 20(R)-ginsenoside Rg3 on the expressions of angiogenesis factors proteins in human lung adenocarcinoma cell line A549 and HUVEC304 cell. Zhongguo Zhong Yao Za Zhi. 2005;30(5):357-60.