Download PDF
Planta Med 2003; 69(5): 459-461
DOI: 10.1055/s-2003-39717
Letter
© Georg Thieme Verlag Stuttgart · New York

Torilin from Torilis japonica, as a New Inhibitor of Testosterone 5α-Reductase

Won Seok Park1 , Eui Dong Son1 , Gae Won Nam1 , Soo Hyun Kim1 , Min Soo Noh1 , Byeong Gon Lee1 , Ih Seop Jang1 , Se Eun Kim2 , Jung Joon Lee2 , Chang Hoon Lee1
  • 1Skin Research Team, Skin Research Institute, Pacific R&D Center Kiheung-eup, Yongin-si, Kyoungg-do, Korea
  • 2Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon, Korea
Further Information

Publication History

Received: September 13, 2002

Accepted: February 9, 2003

Publication Date:
12 June 2003 (online)

    Permissions and Reprints

Abstract

The methanolic extract of the fruits of Torilis japonica showed a potent inhibition against 5α-reductase activity in vitro. Bioassay-guided fractionation of the methanol extract of the fruits followed by repeated silica gel chromatography led to the isolation of an active principle and its structure was identified as torilin on the basis of spectroscopic data. Torilin (IC50 = 31.7 ± 4.23 μM) showed a stronger inhibition of 5α-reductase than α-linolenic acid (IC50 = 160.3 ± 24.62 μM) but was weaker than finasteride. (IC50 = 0.38 ± 0.06 μM). Simple guaiane-type compounds, such as (-)-guaiol and guaiazulene showed weak inhibitory effects on the 5α-reductase activity with IC50 values of f 81.6 μM and 100.8 μM, respectively, while azulene was not active. These results suggest that both degrees of unsaturation and the side-chain in the guaiane skeleton are important for the manifestation of 5α-reductase inhibition.

References

  • 1 Anderson K M, Liao S. Selective retention of dihydrotestosterone by prostatic nuclei.  Nature. 1968;  219 277-9
    PubMedGoogle Scholar
  • 2 Bruchovsky N, Wilson J D. The conversion of testosterone to 5-alpha-androstan-17-beta-ol-3-one by rat prostate in vivo and in vitro .  Journal of Biological Chemistry. 1968;  243 2012-21
    PubMedGoogle Scholar
  • 3 Liao S , Kokontis J, Sai T, Hiipakka R A. Androgen receptors: structures, mutations, antibodies and cellular dynamics.  Journal of Steroid Biochemistry and Molecular Biology. 1989;  34 41-51
    PubMedGoogle Scholar
  • 4 Liang T, Cascieri M A, Cheung A H, Reynolds G F, Rasmusson G H. Species differences in prostatic steroid 5-alpha-reductases of rat, dog, and human.  Endocrinology. 1985;  117 571-9
    PubMedGoogle Scholar
  • 5 Bramson H N, Hermann D, Batchelor K W, Lee F W, James M K, Frye S V. Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR.  Journal of Pharmacology and Experimental Therapeutics. 1997;  282 1496-502
    PubMedGoogle Scholar
  • 6 Liao S, Hiipakka R A. Selective inhibition of steroid 5-alpha-reductase isozymes by tea epicatechin-3-gallate and epigallocatechin-3-gallate.  Biochemistry and Biophysical Research Communication. 1995;  214 833-8
    PubMedGoogle Scholar
  • 7 Shimizu K, Fukuda M, Kondo R, Sakai K. The 5-alpha-reductase inhibitory components from heartwood of Artocarpus incisus: structure-activity investigations.  Planta Medica. 2000;  66 16-9
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Ishiguro K, Oku H, Kato T. Kato Testosterone 5alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina .  Phytotherapy Research. 2000;  14 54-6
    CrossrefPubMedGoogle Scholar
  • 9 Seo E K, Kim K H, Kim M K, Cho M H, Choi E, Kim K, Mar W. Inhibitors of 5-alpha-reductase type I in LNCap cells from the roots of Angelica koreana .  Planta Medica. 2002;  68 162-3
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Liang T, Liao S. Inhibition of steroid 5-alpha-reductase by specific aliphatic unsaturated fatty acids.  Biochemistry Journal. 1992;  285 557-62
    PubMedGoogle Scholar
  • 11 Ye F, Imamura K, Imanish N, Rhodes L, Uno H. Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.  Skin Pharmacology. 1997;  10 288-97
    PubMedGoogle Scholar
  • 12 Chikamatsu H, Maeda M, Nakazaki M. Structure of torilin.  Tetrahedron. 1969;  25 4751-65
    CrossrefPubMedGoogle Scholar
  • 13 Kang S S, Lee E B, Kim T H, Kim K R, Jung J H. The NMR assignment of torilin from Torilis japonica .  Archives of Pharmaceutical Research. 1994;  17 284-6
    PubMedGoogle Scholar
  • 14 Kim S E, Kim Y H, Kim Y C, Lee J J. Torilin, a sesquiterpene from Torilis japonica, reverses multidrug-resistance in cancer cells.  Planta Medica. 1998;  64 332-4
    PubMedGoogle Scholar
  • 15 Kim M S, Lee Y M, Moon E J, Kim S E, Lee J J, Kim K W. Anti-angiogenic activity of torilin, a sesquiterpene compound isolated from Torilis japonica .  International Journal of Cancer. 1998;  87 269-75
    PubMedGoogle Scholar
  • 16 Jones C D, Audia J E, Lawhorn D E, McQuaid L A, Neubauer B L, Pike A J, Pennington P A, Stamm N B, Toomey R E, Hirsh K S. Nonsteroidal inhibitors of human type I steroid 5-alpha-reductase.  Journal of Medicinal Chemistry. 1993;  36 421-3
    CrossrefPubMedGoogle Scholar
  • 17 Nakayama O, Yagi M, Tanaka M, Kiyoto S, Okuhara M, Kohsaka M. WS-9659 A and B, novel testosterone 5α-reductase inhibitors isolated from a streptomyces.  Journal of Antibiotics.. 1989;  32 1221-9
    PubMedGoogle Scholar

Dr. Chang Hoon Lee

Skin Research Institute

Pacific R&D Center

314-1 Bora-ri

Kiheung-eup

Yongin-si

Kyoungg-do

Korea

Fax: +82-31-282-6063

Email: chlee@pacific.co.kr

      >