Planta Med 2006; 72(3): 193-198
DOI: 10.1055/s-2005-916176
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Suppression of Fas-Mediated Apoptosis of Keratinocyte Cells by Chikusetsusaponins Isolated from the Roots of Panax japonicus

Kanako Hosono-Nishiyama1 , Tsukasa Matsumoto1 , 2 , Hiroaki Kiyohara1 , 2 , Ai Nishizawa3 , Takamasa Atsumi3 , Haruki Yamada1 , 2
  • 1Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan
  • 2Oriental Medicine Research Center, The Kitasato Institute, Tokyo, Japan
  • 3Ivy Cosmetics Co. Ltd., Saitama, Japan
Further Information

Publication History

Received: March 18, 2005

Accepted: July 25, 2005

Publication Date:
05 December 2005 (online)

Abstract

Fas-mediated apoptotic cell death of a human keratinocyte cell line, HaCaT cells, and of a murine keratinocyte cell line, Pam212 cells, was suppressed by pre-treatment with a methanol extract from the roots of Panax japonicus C.A. Meyer. Activity-guided fractionation led to the isolation of chikusetsusaponins IV, IVa, V and polysciasaponin P5 as the active ingredients. Of these compounds, chikusetsusaponin IV, was most active when applied at a concentration of 12.5 μg/mL. The intracellular hallmark events of apoptosis such as DNA fragmentation and chromatin condensation were significantly reduced by the treatment with chikusetsusaponin IV. The apoptotic cell death of Jurkat cells was also suppressed by treatment with the active saponins. These results suggest that the use of chikusetsusaponins IV, IVa, V, polysciasaponin P5, or a crude extract of P. japonicus containing these saponins is expected to relieve cutaneous symptoms caused by excessive apoptotic cell death in the skin through the Fas/FasL pathway.

References

  • 1 Walczak H, Krammer P H. The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems.  Exp Cell Res. 2000;  256 58-66
  • 2 Wehrli P, Viard I, Bullani R, Tschopp J, French L E. Death receptors in cutaneous biology and disease.  J Invest Dermatol. 2000;  115 141-8
  • 3 Trautmann A, Akdis M, Kleemann D, Altznauer F, Simon H U, Graeve T. et al . T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis.  J Clin Invest. 2000;  106 25-35
  • 4 Baima B, Sticherling M. Apoptosis in different cutaneous manifestations of lupus erythematosus.  Br J Dermatol. 2001;  144 958-66
  • 5 Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D. et al . Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.  Science. 1998;  282 490-3
  • 6 Leverkus M, Yaar M, Gilchrest B A. Fas/Fas ligand interaction contributes to UV-induced apoptosis in human keratinocytes.  Exp Cell Res. 1997;  232 255-62
  • 7 Murphy G, Young A R, Wulf H C, Kulms D, Schwarz T. The molecular determinants of sunburn cell formation.  Exp Dermatol. 2001;  10 155-60
  • 8 Gilhar A, Ullmann Y, Karry R, Shalaginov R, Assy B, Serafimovich S, Kalish R S. Aging of human epidermis: reversal of aging changes correlates with reversal of keratinocyte Fas expression and apoptosis.  J Gerontol A Biol Sci Med Sci. 2004;  59 411-5
  • 9 Wang X, Bregegere F, Soroka Y, Kayat A, Redziniak G, Milner Y. Enhancement of Fas-mediated apoptosis in ageing human keratinocytes.  Mech Ageing Dev. 2004;  125 237-49
  • 10 Haake A R, Roublevskaia I, Cooklis M. Apoptosis: a role in skin aging?.  J Investig Dermatol Symp Proc. 1998;  3 28-35
  • 11 Saito H, Lee Y M, Takagi K, Shibata S, Shoji J, Kondo N. Pharmacological studies of Panacis japonici rhizoma. I.  Chem Pharm Bull. 1977;  25 1017-25
  • 12 Lee Y, Saito H, Takagi K, Shibata S, Shoji J. Pharmacological studies of Panacis japonici rhizoma. II.  Chem Pharm Bull. 1977;  25 1391-8
  • 13 Zou K, Zhu S, Meselhy M R, Tohda C, Cai S, Komatsu K. Dammarane-type saponins from Panax japonicus and their neurite outgrowth activity in SK-N-SH cells.  J Nat Prod. 2002;  65 1288-92
  • 14 Boukamp P, Petrussevska R T, Breitkreutz D, Hornung J, Markham A, Fusenig N E. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.  J Cell Biol. 1988;  106 761-71
  • 15 Yuspa S H, Hawley-Nelson P, Koehler B, Stanley J R. A survey of transformation markers in differentiating epidermal cell lines in culture.  Cancer Res. 1980;  40 4694-703
  • 16 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
  • 17 Page B, Page M, Noel C. A new fluorometric assay for cytotoxicity measurements in vitro .  Int J Oncol. 1993;  3 473-6
  • 18 Nie R L, Morita T, Kasai R, Zhou J, Wu C Y, Tanaka O. Saponins from Chinese medicinal plants. (I). Isolation and structures of hemslosides.  Planta Med. 1984;  50 322-7
  • 19 Kinjo J, Suyama K, Nohara T. Triterpenoidal saponins from Dumasia truncata .  Phytochemistry. 1995;  40 1765-7
  • 20 Marouf A, Desbene S, Khanh T C, Wagner H, Correia M, Chauffert B, Lacaille-Dubois M A. Triterpene saponins from the roots of Achyranthes bidentata .  Pharm Biol. 2001;  39 263-7

Prof. Dr. Haruki Yamada

Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences

Kitasato University

5-9-1 Shirokane

Minato-ku

Tokyo 108-8641

Japan

Email: yamada@lisci.kitasato-u.ac.jp

    >