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

© Georg Thieme Verlag Stuttgart · New York

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
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Publication History

April 19, 2001

June 24, 2001

Publication Date:
22 February 2002 (online)

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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.

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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 6 Russell D W, Wilson J D. Steroid 5 alpha-reductase: two genes/two enzymes.  Annu. Rev. Biochem.. 1994;  63 5-61
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 13 Steck M, Mazurek M. Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects.  Lloydia. 1972;  35 418-39
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 16 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J. Immunol. Methods. 1983;  65 55-63
    CrossrefPubMedGoogle Scholar

Prof. Ph. D. Woongchon Mar

Natural Products Research Institute

Seoul National University

Seoul 110-460

Korea

Phone: +82-2-740-8911

Fax: +82-2-3672-5488

Email: mars@snu.ac.kr