Influence of epilobium angustifolium extract on 5α-reductase type 2 and mapk3 kinase gene expression in rats prostates

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The aim of this study was to investigate the influence of standardized Epilobium angustifolium L. extract [100 mg/kg/day, p.o.] on the expression level of 5α-reductase type 2 (Srd5ar2) mRNA and Mapk3 mRNA a representative of non-genomic xenobiotics signaling pathway. It was shown that plant extract from the E. angustifolium showed a slight tendency to reduce prostate weight in hormonally induced animals (p>0.05) and in testosterone induced animals receiving both, extract and finasteride (p<0.05). Finasteride in rats induced by testosterone caused a smaller decrease in the level of mRNA 5α-steroid reductase 2 (SRd5ar2), than in rats treated with the hormone and studied plant extracts. In general, an increase in the amount of MAPK3 mRNAs in testosterone-induced groups of rats receiving tested plant extract with or without finasteride was observed, while the expression of type 2 5α-steroid reductase decreased (p<0.05). Further experimental studies should be performed in order to understand the molecular basis of interactions, the efficacy and safety of tested plant extracts.

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  • 1. Elterman DS Lawrentschuk N Guns E Hersey K Adomat H Wood CA Fleshner N. Investigating contamination of phytotherapy products for benign prostatic hyperplasia with α-blockers and 5α-reductase inhibitors. J Urol 2010; 183(5):2085-9.

  • 2. Yamaguchi O. Latest treatment for lower urinary tract dysfunction: therapeutic agents and mechanism of action. Int J Urol 2013; 20(1):28-39.

  • 3. Lowe FC Fagelman E. Phytotherapy in the treatment of benign prostatic hyperplasia. Curr Opin Urol 2002; 12(1):15-8.

  • 4. Von Löw EC Perabo FG Siener R Müller SC. Review. Facts and fiction of phytotherapy for prostate cancer: a critical assessment of preclinical and clinical data. In Vivo 2007; 21(2):189-204.

  • 5. Dedhia RC McVary KT. Phytotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2008; 179(6):2119-25.PDR for Herbal Medicines. 4th ed. Thompson Healtcare Inc. USA 2007:903-4.

  • 6. Van-Hellemont J. Compedium de Phytotherapie. Association Pharmaceutique Brussels 1986.

  • 7. Wichtl M. Herbal Drug and Phytopharmaceuticals 3th ed. Medpharm GmbH Stuttgart 2004.

  • 8. Hevesi BT Houghton PJ Habtemariam S Kery A. Antioxidant and anti-inflammatory effect of Epilobium parviflorum. Schreb Phytother Res 2009; 23(5):719-24.

  • 9. Kujawski R Bartkowiak-Wieczorek J Ożarowski M Bogacz A Cichocka J Karasiewicz M Mrozikiewicz PM. Studies on phytochemical profile of plant materials and extracts derived from aerial parts of Epilobium sp. - a minireview. Herba Pol 2011; 57(4):25-34.

  • 10. Stolarczyk M Naruszewicz M Kiss AK. Extracts from Epilobium sp. herbs induce apoptosis in human hormone-dependent prostate cancer cells by activating the mitochondrial pathway. J Pharm Pharmacol 2013; 65(7):1044-54.

  • 11. Hevesi TB Blazics B Kery A. Polyphenol composition and antioxidant capacity of Epilobium species. J Pharm Biomed Anal 2009; 15;49(1):26-31.

  • 12. Bazylko A Kiss AK Kowalski J. High-performance thin-layer chromatography method for quantitative determination of oenothein B and quercetin glucuronide in aqueous extract of Epilobii angustifolii herba. J Chromatogr A 2007; 30;1173(1-2):146-50.

  • 13. Kiss A Kowalski J Melzig MF. Effect of Epilobium angustifolium L. extracts and polyphenols on cell proliferation and neutral endopeptidase activity in selected cell lines. Pharmazie 2006; 61(1):66-9.

  • 14. Granica S Bazylko A Kiss AK. Determination of macrocyclic ellagitannin oenothein B in plant materials by HPLC-DAD-MS: method development and validation. Phytochem Anal 2012; 23(6):582-7.

  • 15. Hiermann A. Bucar F. Studies of Epilobium angustifolium extracts on growth of accessory sexual organs in rats. J Ethnopharmacol 1997; 55(3):179-83.

  • 16. Vitalone A Bordi F Baldazzi C Mazzanti G Saso L Tita B. Anti-proliferative effect on a prostatic epithelial cell line (PZ-HPV-7) by Epilobium angustifolium L. Farmaco 2001; 56(5-7):483-9.

  • 17. Vitalone A McColl J Thome D Costa LG Tita B. Characterization of the effect of Epilobium extracts on human cell proliferation. Pharmacology 2003; 69(2):79-87.

  • 18. Ramstead AG Schepetkin IA Quinn MT Jutila MA. Oenothein B a cyclic dimeric ellagitannin isolated from Epilobium angustifolium enhances IFNγ production by lymphocytes. PLoS One 2012; 7(11):e50546.

  • 19. Krakurt S Semiz A Celik G Gencler-Ozkan AM. Sen A. Adali O. Epilobium hirsutum alters xenobiotic metabolizing CYP1A1 CYP2E1 NQO1 and GPx activities mRNA and protein levels in rats. Pharm Biol 2013; 51(5):650-8.

  • 20. Stolarczyk M Piwowarski JP Granica S Stefańska J Naruszewicz M Kiss AK. Extracts from Epilobium sp. Herbs Their Components and Gut Microbiota Metabolites of Epilobium Ellagitannins Urolithins Inhibit Hormone-Dependent Prostate Cancer Cells-(LNCaP) Proliferation and PSA Secretion. Phytother Res 2013; doi:10.1002.

  • 21. Coulson S Rao A Beck SL Steels E Gramotnev H Vitetta L. A phase II randomised double-blind placebo-controlled clinical trial investigating the efficacy and safety of ProstateEZE Max: a herbal medicine preparation for the management of symptoms of benign prostatic hypertrophy. Complement Ther Med 2013; 21(3):172-9.

  • 22. Kujawski R Bogacz A Derebecka-Hołysz N Cichocka J Kujawski J Mikołajczak PŁ Bobkiewicz- Kozłowska T Grześkowiak E Krajewska-Patan A Czerny B Mrozikiewicz PM. Medicinal plants from Epilobium genus - biological and pharmacological properties. Herba Pol 2010; 56(1):66-82.

  • 23. Lesuisse D Berjonneau J Ciot C Devaux P Doucet B Gourvest JF Khemis B Lang C Legrand R Lowinski M Maquin P Parent A Schoot B Teutsch G. Determination of oenothein B as the active 5-α-reductaseinhibiting principle of the folk medicine Epilobium parviflorum. J Nat Prod 1996; 59(5):490-2.

  • 24. Ducrey B Marston A Göhring S Hartmann RW Hostettmann K. Inhibition of 5 α-reductase and aromatase by the ellagitannins oenothein A and oenothein B from Epilobium species. Planta Med 1997; 63(2):111-4.

  • 25. Kujawski R Mrozikiewicz PM Bogacz A Cichocka J Mikołajczak PŁ Czerny B Bobkiewicz-Kozłowska T Grześkowiak E. Influence of standardized extract of Epilobium angustifolium on estrogen receptor α and β expression in in vivo model. Ginekol Pol 2010; 81(8):600-605.

  • 26. Kiss A Kowalski J Melzig MF. Compounds from Epilobium angustifolium inhibit the specific metallopeptidases ACE NEP and APN. Planta Med 2004;70(10):919-23.

  • 27. Foradori CD Werner SB Sandau US Clapp TR Handa RJ. Activation of the androgen receptor alters the intracellular calcium response to glutamate in primary hippocampal neurons and modulates sarco/ endoplasmic reticulum calcium ATPase 2 transcription. Neuroscience 2007; 149:155-164.

  • 28. Benett NC Gardiner RA Hooper JD Johnson DW Gobe GC. Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol 2010; 42(6):813-27.

  • 29. Linja MJ Porkka K Kang Z Savinainen KJ Janne OA Tamela TL Vessella RL Palvimo JJ Visakorpi T. Expression of androgen receptor coregulators in prostate cancer. Clin Cancer Res 2004; 10(3):1032-40.

  • 30. Chmelar R Buchanan G Need EF Tilley W Greenberg NM. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer 2007; 120(4):719-33.

  • 31. Nicholson TM Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past present and future. Differentiation 2011; 82(4-5):84-99.

  • 32. Baron S Manin M Beaudoin C Leotoing L Communal Y Veyssiere G. Androgen receptor mediates nongenomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells. J Biol Chem 2004; 279(15):14579-86.

  • 33. Li J Al-Azzawi F. Mechanism of androgen receptor action. Maturitas 2009; 63(2):142-8.

  • 34. Iehlé C Délos S Guirou O. et al. Human prostatic steroid 5 α-reductase isoforms-a comparative study of selective inhibitors. J Steroid Biochem Mol Biol 1995; 54:273-279.

  • 35. Carson CIII Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urolog. 2003; 61(Suppl. 1):2-7.

  • 36. Gravas S Oelke M. Current status of 5α-reductase inhibitors in the management of lower urinary tract symptoms and BPH. World J Urol 2010; 28(1):9-15.

  • 37. Kosowicz J Miskowiak B Konwerska A Belloni AS Nussdorfer GG Malendowicz LK. Pneumadin in the rat ventral prostate and its hormonal regulation. Hormon. Metab. Res 2004; 36:78-81.

  • 38. Schepetkin IA Kirpotina LN Jakiw L Khlebnikov AI Blaskovich CL Jutila MA Quinn MT. Immunomodulatory activity of oenothein B isolated from Epilobium angustifolium. J Immunol 2009; 183(10):6754-66.

  • 39. Kiss AK Bazylko A Filipek A Granica S Jaszewska E Kiarszys U Kośmider A Piwowarski J. Oenothein B’s contribution to the anti-inflammatory and antioxidant activity of Epilobium sp. Phytomedicine 2011; 18(7):557-60.

  • 40. Azzolina B Ellsworth K Andersson S Geissler W Bull HG. Inhibition of rat α-reductases by finasteride: evidence for isozyme differences in the mechanism of inhibition. J Steroid Biochem Mol Biol 1997; 61:55-64.

  • 41. Kang DI Chung JL. Current status of 5α-reductase inhibitors in prostate disease management. Korean J Urol 2013; 54(4):213-9.

  • 42. Gisleskog PO Hermann D Hammarlund-Udenaes M Karlsson MO. The pharmacokinetic modelling of GI198745 (dutasteride) a compound with parallel linear and nonlinear elimination. Br J Clin Pharmacol 1999; 47:53-8.

  • 43. Stuart JD Lee FW Simpson Noel D Kadwell SH Overton LK Hoffman CR Kost TA Tippin TK Yeager RL Batchelor KW Bramson HN. Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5α-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat. Biochem Pharmacol 2001; 62:933-42.

  • 44. Suzuki R Satoh H Ohtani H Hori S Sawada Y. Saturable binding of finasteride to steroid 5α-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet 2010; 25:208-13.

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