SRC kinase mrna transcription changes in testosterone-induced rat ventral prostate lobes under the influence of epilobium angustifolium extract

Open access


The aim of this study was to investigate the influence of standardized crude aqueous Epilobium angustifolium L. extract [100 mg/kg/day, p.o.] on the expression level of SRC kinase mRNA - a representatives of non-genomics xenobiotics signaling pathway in prostate ventral lobes of testosterone-induced, castrated rats. We have shown that in all analyzed groups induced by testosterone an elevation of SRC kinase mRNA transcription was observed, in comparison to control animals (not receiving the testosterone), (p<0.05). Finasteride in rats induced by testosterone caused the strongest inhibition of SRC mRNA transcription (p<0.05). In rats receiving testosterone and the plant extract a ca. 90% decrease of mRNA level was observed vs. testosterone-induced animals (p<0.05), while in testosterone-induced animals receiving concomitantly E. angustifolium extract and finasteride the observed reduction reached 87.3% (p<0.05).

We did not observed, however, any positive feedback between studied plant extract and finasteride in the inhibitory activity (p<0.05). Further experimental studies should be performed in order to the understanding the molecular basis of interactions, the efficacy and safety of tested plant extract.

1. 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.

2. 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.

3. 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.

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

5. 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.

6. 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.

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

8. Wichtl M. Herbal Drug and Phytopharmaceuticals. 3rd ed. Stuttgart 2004.

9. Van-Hellemont J. Compedium de Phytotherapie. Brussels 1986.

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

11. PDR (Physician’s Desk Reference) for Herbal Medicines 2nd ed. 2000:818.

12. 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.

13. 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-alphareductase- inhibiting principle of the folk medicine Epilobium parviflorum. J Nat Prod 1996; 59(5):490-2.

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

15. Kujawski R, Mrozikiewicz PM, Mikołajczak PŁ, Kuzio G, Bogacz A, Bartkowiak-Wieczorek J, Grześkowiak E, Bobkiewicz-Kozłowska T, Czerny B. Influence of Epilobium angustifolium and Serenoa repens extracts on cytochrome 2D2 and 3A1 expression level in rats. Herba Pol 2010; 56(4):39-51.

16. Kiss A, Kowalski J, Melzig MF. Compounds from Epilobium angustifolium L. inhibit the specific metallopeptidases ACE, NEP and APN. Planta Med 2004; 70:919-923.

17. 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.

18. Foradori CD, Weiser MJ, Handa RJ. Non-genomic actions of androgens. Front Neuroendocrinol 2008; 29(2):169-81.

19. 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.

20. Linja MJ, Porkka KP, 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.

21. 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.

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

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

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

25. Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG. The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1 Mol Cell Biol 1999; 19(12):8383-92.

26. 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.

27. 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.

28. 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.

29. 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.

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

31. Azzolina B, Ellsworth K, Andersson S, Geissler W, Bull HG. Inhibition of rat alpha-reductases by finasteride: evidence for isozyme differences in the mechanism of inhibition. J Steroid Biochem Mol Biol1997; 61:55-64.

32. Tindall DJ, Rittmaster RS. The rationale for inhibiting 5-α-reductase isoenzymes in the prevention and treatment of prostate cancer. J Urol 2008; 179:1235-42.

33. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M. An overview on 5-α-reductase inhibitors. Steroids 2010; 75:109-153.

34. Azzouni F. Mohler J. Role of 5α-reductase inhibitors in prostate cancer prevention and treatment. Urology 2012; 79(6):1197-205.

35. 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; 47:53-58.

36. Stuart JD, Lee FW, Simpson Noel D, Kadwell SH, Overton LK, et al. Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5-α-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat. Biochem Pharmacol 2001; 62: 933-942.

37. Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y. Saturable binding of finasteride to steroid 5-α-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet 2010; 25:208-213.

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

Herba Polonica

From Botanical to Medical Research

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 95 95 4
PDF Downloads 40 40 4