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

Won Seok Park; Eui Dong Son; Gae Won Nam; Soo Hyun Kim; Min Soo Noh; Byeong Gon Lee; Ih Seop Jang; Se Eun Kim; Jung Joon Lee; Chang Hoon Lee

doi:10.1055/s-2003-39717

Planta Med 2003; 69(5): 459-461
DOI: 10.1055/s-2003-39717

Letter

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

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.

Full Text

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