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Planta Med 2006; 72(6): 547-551
DOI: 10.1055/s-2006-941472
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Activity-Guided Isolation of an Antiandrogenic Compound of Pygeum africanum

Sonja Schleich1 , Maria Papaioannou2 , Aria Baniahmad2 , Rudolf Matusch1
  • 1Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, Germany
  • 2Genetisches Institut, Justus-Liebig-Universität Giessen, Giessen, Germany
Further Information

Publication History

Received: September 27, 2005

Accepted: December 20, 2005

Publication Date:
28 April 2006 (online)

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Abstract

Inactivation of the androgen receptor (AR) through androgen ablation and treatment with antiandrogens is a major goal in the therapy for prostate hyperplasia and prostate cancer. Bioactivity-directed fractionation of a selective dichloromethane extract from the stem bark of Pygeum africanum led to the isolation of the antiandrogenic compound atraric acid. Its activity was examined by an androgen receptor responsive reporter gene assay. For lead structure optimization we transformed the natural occurring compound atraric acid into its ethyl, n-propyl and n-butyl esters and their antiandrogenic activities were examined as well. In addition, benzoic acid was isolated. The structures of all compounds were determined and characterized by means of 1H- and 13C-NMR, HR-EI-mass, IR and UV spectroscopy.

Key words

Pygeum africanum - Prunus africana - Rosaceae - atraric acid - benzoic acid - antiandrogenic activity - androgen - hormone therapy

References

  • 1 Bombardelli E, Morazzoni P. Prunus africana (Hook. f.) Kalkm.  Fitoterapia. 1997;  68 205-18
    PubMedSearch in Google Scholar
  • 2 Ishani A, MacDonald R, Nelson D, Rutks I, Wilt T J. Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis.  Am J Med. 2000;  109 654-64
    CrossrefPubMedSearch in Google Scholar
  • 3 Gonzalgo M L, Isaacs W B. Molecular pathways to prostate cancer.  J Urol. 2003;  170 2444-52
    CrossrefPubMedSearch in Google Scholar
  • 4 Yablonsky F, Nicolas V, Riffaud J P, Bellamy F. Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts.  J Urol. 1997;  157 2381-7
    CrossrefPubMedSearch in Google Scholar
  • 5 Anim J T, Udo C, John B. Characterisation of inflammatory cells in benign prostatic hyperplasia.  Acta Histochem. 1998;  100 439-49
    PubMedSearch in Google Scholar
  • 6 Paubert-Braquet M, Cave A, Hocquemiller R, Delacroix D, Dupont C, Hedef N. et al . Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolites from human polymorphonuclear cells.  J Lipid Mediat Cell Signal. 1994;  9 285-90
    PubMedSearch in Google Scholar
  • 7 Mathe G, Hallard M, Bourut C H, Chenu E. A Pygeum africanum extract with so-called phyto-estrogenic action markedly reduces the volume of true and large prostatic hypertrophy.  Biomed Pharmacother. 1995;  49 341-3
    CrossrefPubMedSearch in Google Scholar
  • 8 Mathe G, Orbach-Arbouys S, Bizi E, Court B. The so-called phyto-estrogenic action of Pygeum africanum extract.  Biomed Pharmacother. 1995;  49 339-40
    CrossrefPubMedSearch in Google Scholar
  • 9 Longo R, Tira S. Constituents of Pygeum africanum bark.  Planta Med. 1981;  42 195-6
    PubMedSearch in Google Scholar
  • 10 Fourneau C, Hocquemiller R, Cavé A. Triterpenes from Prunus africana bark.  Phytochemistry. 1996;  42 1387-9
    CrossrefPubMedSearch in Google Scholar
  • 11 McClure M W. An overview of holistic medicine and complementary and alternative medicine for the prevention and treatment of BPH, prostatitis, and prostate cancer.  World J Urol. 2002;  20 273-84
    CrossrefPubMedSearch in Google Scholar
  • 12 Gast A, Schneikert J, Cato A C. N-terminal sequences of the human androgen receptor in DNA binding and transrepressing functions.  J Steroid Biochem Mol Biol. 1998;  65 117-23
    CrossrefPubMedSearch in Google Scholar
  • 13 Dotzlaw H, Moehren U, Mink S, Cato A C, Iniguez Lluhi J A, Baniahmad A. The amino terminus of the human AR is target for corepressor action and antihormone agonism.  Mol Endocrinol. 2002;  16 661-73
    CrossrefPubMedSearch in Google Scholar
  • 14 Dotzlaw H, Papaioannou M, Moehren U, Claessens F, Baniahmad A. Agonist-antagonist induced coactivator and corepressor interplay on the human androgen receptor.  Mol Cell Endocrinol. 2003;  213 79-85
    CrossrefPubMedSearch in Google Scholar
  • 15 Brehm L, Stoeckli-Evans H, Tabacchi R. The crystal structure of methyl β-orcinol-carboxylate ( = methyl 2,4-dihydroxy-3,6-dimethylbenzoate).  Helv Chim Acta. 1983;  66 824-7
    CrossrefPubMedSearch in Google Scholar
  • 16 Gormann R, Kaloga M, Li X C, Ferreira D, Bergenthal D, Kolodziej H. Furanonaphthoquinones, atraric acid and a benzofuran from the stem barks of Newbouldia laevis .  Phytochemistry. 2003;  64 583-7
    CrossrefPubMedSearch in Google Scholar
  • 17 Lee S S, Chang S M, Chen C H. Chemical constituents from Alseodaphne andersonii .  J Nat Prod. 2001;  64 1548-51
    CrossrefPubMedSearch in Google Scholar
  • 18 Nagumo S, Ishizawa S, Nagai M, Inoue T. Studies on the constituents of Aceraceae plants. XIII. Diarylheptanoids and other phenolics from Acer nikoense .  Chem Pharm Bull. 1996;  44 1086-9
    PubMedSearch in Google Scholar
  • 19 Bardón A, Bovi Mitre G, Kamiya N, Toyota M, Asakawa Y. Eremophilanolides and other constituents from the Argentine liverwort Frullania brasiliensis .  Phytochemistry. 2002;  59 205-13
    CrossrefPubMedSearch in Google Scholar
  • 20 Bourgeois G, Suire C, Vivas N. Atraric acid, a marker for epiphytic lichens in the wood used in cooperage: identification and quantification by GC/MS/(MS).  Analysis. 1999;  27 281-3
    PubMedSearch in Google Scholar
  • 21 Ahad A M, Goto Y, Kiuchi F, Tsuda Y, Kondo K, Sato T. Nematocidal principles in ”oakmoss absolute” and nematocidal activity of 2,4-dihydroxybenzoates.  Chem Pharm Bull. 1991;  39 1043-6
    PubMedSearch in Google Scholar
  • 22 National Institute of Advanced Industrial Science and Technology, Japan. SDBS database. Available at http://www.aist.go.jp/RIODB/SDBS/menu-e.html. Accessed in 2004. 
  • 23 Ishikawa T, Nishigaya K, Takami K, Uchikoshi H, Chen I S, Tsai I L. Isolation of salicin derivates from Homalium cochinchinensis and their antiviral activities.  J Nat Prod. 2004;  67 659-63
    CrossrefPubMedSearch in Google Scholar
  • 24 Fleischer T C, Waigh R D, Waterman P G. A novel retrodihydrochalcone from the stem bark of Uvaria mocoli .  Phytochemistry. 1997;  47 1387-91
    PubMedSearch in Google Scholar
  • 25 Coquoz J L, Buchala A, Métraux J P. The biosynthesis of salicylic acid in potato plants.  Plant Physiol. 1998;  117 1095-101
    CrossrefPubMedSearch in Google Scholar
  • 26 Hertweck C, Jarvis A P, Xiang L, Moore B S, Oldham N J. A mechanism of benzoic acid biosynthesis in plants and bacteria that mirrors fatty acid β-oxidation.  Chembiochem. 2001;  10 784-6
    PubMedSearch in Google Scholar
  • 27 Tremblay G C, Qureshi I A. The biochemistry and toxicology of benzoic acid metabolism and its relationship to the elimination of waste nitrogen.  Pharmacol Ther. 1993;  60 63-90
    CrossrefPubMedSearch in Google Scholar

Aria Baniahmad

Genetisches Institut

Justus-Liebig-Universität Giessen

Heinrich-Buff-Ring 58-62

35392 Giessen

Germany

Phone: +49-641-99-35468

Fax: +49-641-99-35469

Email: aban@mti.uni-jena.de

    www.thieme-connect.de/ejournals/toc/plantamedica