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DOI: 10.1055/s-2003-39717
Torilin from Torilis japonica, as a New Inhibitor of Testosterone 5α-Reductase
Publication History
Received: September 13, 2002
Accepted: February 9, 2003
Publication Date:
12 June 2003 (online)
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
- 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
- 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
- 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
- 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
- 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
- 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
- 8 Ishiguro K, Oku H, Kato T. Kato Testosterone 5alpha-reductase inhibitor bisnaphthoquinone derivative from Impatiens balsamina . Phytotherapy Research. 2000; 14 54-6
- 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
- 10 Liang T, Liao S. Inhibition of steroid 5-alpha-reductase by specific aliphatic unsaturated fatty acids. Biochemistry Journal. 1992; 285 557-62
- 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
- 12 Chikamatsu H, Maeda M, Nakazaki M. Structure of torilin. Tetrahedron. 1969; 25 4751-65
- 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
- 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
- 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
- 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
- 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
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