Inhibitors of 5α -Reductase Type I in LNCaP Cells from the Roots of Angelica koreana

Eun-Kyoung Seo; Kyeong Ho Kim; Min Ki Kim; Myung-Haing Cho; Eun Wook Choi; Ki Nam Kim; Woongchon Mar

doi:10.1055/s-2002-20258

Planta Medica, Inhaltsverzeichnis

Planta Med 2002; 68(2): 162-163
DOI: 10.1055/s-2002-20258

Letter

Inhibitors of 5α -Reductase Type I in LNCaP Cells from the Roots of Angelica koreana

Eun-Kyoung Seo¹ , Kyeong Ho Kim² , Min Ki Kim² , Myung-Haing Cho³ , EunWook Choi⁴ , KiNam Kim⁴ , Woongchon Mar⁴

¹Natural Products Chemistry Laboratory, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea
²College of Pharmacy, Kangwon National University, Chunchon, Korea
³NIAST, RDA and College of Veterinary Medicine, Seoul National University, Suwon, Korea
⁴Natural Products Research Institute, Seoul National University, Seoul, Korea

Abstract

A prenylated coumarin, osthenol (1) and a sesquiterpene, bisabolangelone (2) have been isolated as active principles with 5α-reductase type I inhibitory effects in LNCaP cells from the roots of Angelica koreana Max. by bioassay-guided chromatographic fractionation. Osthenol exhibited a highly potent inhibitory activity on 5α-reductase type I in LNCaP cells with an IC₅₀ value of 0.1 μg/ml, which is about 200 times more potent than the positive control, finasteride (IC₅₀ = 19.8 μg/ml). Bisabolangelone also inhibited the activity of 5α-reductase type I in LNCaP cells (IC₅₀ = 11.6 μg/ml), indicating that these compounds are possible candidates for the development of new drugs to treat human endocrine disorders associated with overproduction of DHT by 5 α-reductase type I. In addition, four compounds isooxypeucedanin, oxypeucedanin hydrate, oxypeucedanin and isoimperatorin were also isolated and found to be inactive in the 5α-reductase assay systems used in the present study.

Volltext

Referenzen

References

1 Liu J H, Xu S X, Yao X S, Kobayashi H. Angelol-type coumarins from Angelica pubescens F. biserrata and their inhibitory effect on platelet aggregation. Phytochemistry;. 1995; 39 1099-101
2 Kwon Y S, Kobayashi A, Kajiyama S I, Kawazu K, Kanzaki H, Kim C M. Antimicrobial constituents of Angelica dahurica roots. Phytochemistry. 1997; 44 887-9
3 Matsuda H, Murakami T, Kageura T, Ninomiya K, Toguchida I, Nishida N, Yoshikawa M. Hepatoprotective and nitric oxide production inhibitory activities of coumarin and polyacetylene constituents from the roots of Angelica furcijuga . Bioorg. Med. Chem. Lett.. 1998; 18 2191-6
4 Choi Y E, Ahn H, Ryu J H. Polyacetylenes from Angelica gigas and their inhibitory activity on nitric oxide synthesis in activated macrophages. Biol. Pharm. Bull.. 2000; 23 884-6
5 Zhui Y, Jing-Ping O Y, Yongming L, Lei W, Shuzheng T, Hailu Y, Hanqiao Z, Xiaoho Y. Experimental study of the antiatherogenesis effect of Chinese medicine angelica and its mechanisms. Clin Hemorheol Microcirc.. 2000; 22 305-10
6 Russell D W, Wilson J D. Steroid 5 alpha-reductase: two genes/two enzymes. Annu. Rev. Biochem.. 1994; 63 5-61
7 Hirsch K S, Jones C D, Audia J E, Andersson S, McQuaid L, Stamm N B, Meubauer B L, Pennington P, Toomey R E, Russel D W. LY191704: A selective, nonsteroidal of human steroid 5α-reductase type I. Proc. Natl. Acad. Sci. USA. 1993; 90 5277-81
8 Negri-Cesi P, Poletti A, Colciago A, Magni P, Motta M. Presence of 5α-reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue. The Prostate. 1998; 34 283-91
9 Macias F A, Hernandez-Galan R, Massanet G M, Rodriquez-Luis F, Vasquez M, Salva J. Carbon-13 NMR of coumarins. V. 3-Prenylated coumarins. Magn. Reson. Chem.. 1990; 28 732-5
10 Seo E -K, Chai H B, Chagwedera T E, Farnsworth N R, Cordell G A, Pezzuto J M, Kinghorn A D. 5-(4-Hydroxyphenethenyl)-4,7-dimethoxycoumarin, a new constituent of Monotes engleri . Planta Med.. 2000; 66 182-4
11 Kim T J, Lee S I, Yoon Y S, Ko J S. A study on structure and quantitation of furanocoumarins from Angelica koreana Max. J. Kor. Soc. Anal. Sci.. 1989; 2 337-45
12 Bae K H, Ji J M, Kang J S, Ahn B Z. A cytotoxic component from Angelicae koreanae radix against L1210 and HL-60 cells. Arch. Pharm. Res.. 1994; 17 45-7
13 Steck M, Mazurek M. Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects. Lloydia. 1972; 35 418-39
14 Bergendorff O, Dekermendjian K, Nielsen M, Shan R, Witt R, Ai J, Sterner O. Furanocoumarins with affinity to brain benzodiazepine receptors in vitro . Phytochemistry. 1997; 44 1121-4
15 Smith C M, Ballard S A, Worman N, Buettner R, Masters J R. 5 Alpha-reductase expression by prostate cancer cell lines and benign prostatic hyperplasia in vitro . J. Clinical Endo. Metabol.. 1996; 81 1361-6
16 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983; 65 55-63

Prof. Ph. D. Woongchon Mar

Natural Products Research Institute

Seoul National University

Seoul 110-460

Korea

Telefon: +82-2-740-8911

Fax: +82-2-3672-5488

eMail: mars@snu.ac.kr