Advertisement

Molecular Biology Reports

, Volume 46, Issue 2, pp 1855–1871 | Cite as

The effects of Pueraria mirifica extract, diadzein and genistein in testosterone-induced prostate hyperplasia in male Sprague Dawley rats

  • Jamaludin MohamadEmail author
  • Siti Saleha Masrudin
  • Zazali Alias
  • Nur Airina Muhamad
Original Article
  • 143 Downloads

Abstract

Pueraria mirifica (PM) is a medicinal plant native to Thailand contained high amount of phytoestrogen and possesses anticancer activity. This study reports the effect of P. mirifica extract, phytoestrogen of diadzein and genistein for its benign prostate hyperplasia properties in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The P. mirifica extract was evaluated for its total phenols, flavonoid and antioxidant activity using DPPH, FRAP and metal chelating assay. The assessment of P. mirifica, diadzein and genistein against benign prostate hyperplasia was determined in testosterone-induced prostate hyperplasia in male Sprague Dawley rats. The total phenol was higher than flavonoid but showed low antioxidant activity of DPPH, FRAP and metal chelating. The aqueous PM extract at 1000 mg/kg significantly increased testosterone levels in testosterone-induced rats by 13% while diadzein and genistein increased it by 11% and 17% respectively. However, levels of FSH, LH, triglyceride and HDL are not affected by the oral administration of PM, diadzein and genistein to the rats. Similarly, total protein, albumin, globulin, total bilirubin, conjugated bilirubin, alkaline phosphatase, alanine aminotransferase, AST, and G-glutamyltransferase showed no significant difference as compared with negative control rats. The body weight of the rats, testis, kidney and liver showed no toxic effect. The zinc content increased significantly and the zinc transporter gen of ZnT4 and ZIP4 highly expressed suggesting that the PM, diadzein and genistein plays essential role in modulating prostate zinc homeostasis. Similarly, the expression of IL-6, AR and ER was significantly reduced indicating functioning in regulation of prostate growth and acts as anti-inflammatory role in preventing BPH. In conclusion, the results indicated that PM reduced BPH and contributed to the regulation in the zinc transport expression of the prostate cells in the benign prostate hyperplasia (BPH).

Keywords

Antioxidant Phytoestrogen Prostate hyperplasia Pueraria mirifica Testosterone Zinc transport 

Abbreviations

PM

Pueraria mirifica

BPH

Benign prostatic hyperplasia

PW

Prostatic weight

PI

prostatic index

mRNA

Messenger ribonucleic acid

DPPH

2,2-diphenyl-1-picrylhydrazyl

FRAP

Ferric ion reducing antioxidant power

FSH

Follicle-stimulating hormone

LH

Luteinizing hormone

HDL

High density lipid

AST

Aspartate aminotransferase

ZnT4

Zinc transporter ZnT4

ZIP4

Zrt-Irt-like protein

IL-6

Interleukin 6

AR

Androgen receptor

ER

Estrogen receptor

Notes

Acknowledgements

We are grateful to the Institute of Biological Sciences for providing laboratory facilities to conduct the research works.

Funding

This research was supported by the University of Malaya, Grant No. PV010-2012A.

Compliance with ethical standards

Conflict of interest

The author declare that they have no conflict of interest.

Ethical approval

This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of National Institute of Health. The protocol was approved by the University of Malaya Animal Care and Use Committee (No: ISB/30/05/2012/SSM(R)).

Informed consent

Informed consent was obtained from all researches participates in the study.

References

  1. 1.
    Beduschi MC, Beduschi R, Oesterling JE (1999) Alpha-blockade therapy for benign prostatic hyperplasia: from a nonselective to a more selective alpha1A- adrenergic antagonist. Urology 51:861–872Google Scholar
  2. 2.
    Napalkov P, Maisonneuve P, Boyle P (1995) Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia. Urology 46(3A):41–46PubMedGoogle Scholar
  3. 3.
    Flannery MT, Ramsdell J, Ranhosky A, Davidai G, Ruoff G (2006) Efficacy and safety of tamsulosin for benign prostatic hyperplasia: clinical experience in the primary care setting. Curr Med Res Opin 22:721–730PubMedGoogle Scholar
  4. 4.
    Russell DW, Wilson JD (1994) Steroid 5-reductase: two genes/two enzymes. Ann Rev Clin Biochem 63:25–26Google Scholar
  5. 5.
    Vaughan D, Imperato-McGinley J, McConnell J, Matsumoto AM, Bracken B (2002) Long-term (7–8-year) experience with finasteride in men with benign prostatic hyperplasia. Urology 60:1040–1044PubMedGoogle Scholar
  6. 6.
    Uygur MC, Gur E, Arik AI, Altug U, Erol D (1998) Erectile dysfunction following treatments of benign prostatic hyperplasia: a prospective study. Andrologia 30:5–10PubMedGoogle Scholar
  7. 7.
    Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional prevention of cancer study group. JAMA 276:1957–1963PubMedGoogle Scholar
  8. 8.
    Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC (2002) A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 94:391–398PubMedGoogle Scholar
  9. 9.
    Rohrmann S, Giovannucci E, Willett WC, Platz EA (2007) Fruit and vegetable consumption, intake of micronutrients, and benign prostatic hyperplasia in US men. Am J Clin Nutr 85:523–529PubMedGoogle Scholar
  10. 10.
    Kristal AR, Stanford JL, Cohen JH, Wicklund K, Patterson RE (1999) Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Cancer Epidemiol Biomark Preview 8:887–892Google Scholar
  11. 11.
    Takeuchi T, Nishii O, Okamura T, Yaginuma T (1991) Effect of paeoniflorin, glycyrrhizin and glycyrrhetic acid on ovarian androgen production. Am J Chin Med 19(1):73–78PubMedGoogle Scholar
  12. 12.
    Grant P, Dworakowska D (2012) Tea and Diabetes: the laboratory and the real world. In: Preedy V (ed) Tea in health & disease prevention. Elsevier Academic Press, New YorkGoogle Scholar
  13. 13.
    Boyle P, Robertson C, Lowe F, Roehrborn C (2004) Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia. BJU Int 93(6):751–756PubMedGoogle Scholar
  14. 14.
    Wilt T, Ishani A, Mac Donald R (2002) Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Revis 3:CD001423Google Scholar
  15. 15.
    Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggbald J (1997) Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology 138:863–870PubMedGoogle Scholar
  16. 16.
    Setchell KDR, Cassidy A (1999) Dietary isoflavones—biological effects and relevance to human health. J Nutr 129:758S–767SPubMedGoogle Scholar
  17. 17.
    Clemens B, Karin AP, Arin P, Klaus P, Marco A (2004) Phytoestrogen tissue levels in benign prostatic hyperplasia and prostate cancer and their association with prostatic diseases. Urology 64(4):707–711Google Scholar
  18. 18.
    Denis L, Morton MS, Griffiths K (1999) Diet and its preventive role in prostatic diseases. Eur Urol 35:377–387PubMedGoogle Scholar
  19. 19.
    Griffiths K, Denis L, Turkes A (2002) Oestrogens, phytoestrogens and the pathogenesis of prostatic diseases. Martin Dunitz, LondonGoogle Scholar
  20. 20.
    Geller J, Sionit L, Partido C, Li L, Tan X (1998) Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 34:75–79PubMedGoogle Scholar
  21. 21.
    Hsu A, Bray TM, Helferich WG, Doerge DR, Ho E (2010) Differential effects of whole soy extract and soy isoflavones on apoptosis in prostate cancer cells. Exp Biol Med 235:90–97Google Scholar
  22. 22.
    Stephens FO (1999) The rising incidence of breast cancer in women and prostate cancer in men. Dietary influences: a possible preventative role for nature’s sex hormone modifiers: the phytoestrogens. Oncol Rep 6:865–870PubMedGoogle Scholar
  23. 23.
    Choi YH, Lee WH, Park KY, Zhang I (2000) p53-Independent induction of p21 (WAF1/CIPI), reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn J Cancer Res 91:164–173PubMedPubMedCentralGoogle Scholar
  24. 24.
    Vance TM, Su J, Fontham ET, Koo SI, Chun OK (2013) Dietary antioxidants and prostate cancer. Nutr Cancer 65(6):793–801PubMedGoogle Scholar
  25. 25.
    Lall RK, Syed DN, Khan MI, Adhami VM, Gong Y, Lucey JA, Mukhtar H (2015) Dietary polyphenols in prevention and treatment of prostate cancer. Int J Mol Sci 16:3350–3376PubMedPubMedCentralGoogle Scholar
  26. 26.
    Taylor KM, Morgan HE, Smart K, Zahar NM, Pumford S, Ellis IO, Nicholson RI (2007) The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Mol Med 13(7–8):396–406PubMedPubMedCentralGoogle Scholar
  27. 27.
    Cousins RJ, Liuzzi JP, Lichten LA (2006) Mammalian zinc transport, trafficking, and signals. J Biol Chem 281:24085–24089PubMedGoogle Scholar
  28. 28.
    Eide DJ (2006) Zinc transporters and the cellular trafficking of zinc. Biochim Et Biophys Acta 1763(7):711–722Google Scholar
  29. 29.
    Liuzzi JP, Cousins RJ (2004) Mammalian zinc transporters. Annu Rev Nutr 24:151–172PubMedGoogle Scholar
  30. 30.
    Hurley LS (1981) Teratogenic aspects of manganese, zinc, and copper nutrition. Physiol Rev 61(2):249–295PubMedGoogle Scholar
  31. 31.
    Michael F, Leitzmann MJ, Stampfer K, Wu (2003) Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 95(13):1004–1007Google Scholar
  32. 32.
    Christudoss P, Selvakumar R, Fleming JJ, Gopala Krishnan G (2011) Zinc status of patients with benign prostatic hyperplasia and prostate carcinoma. Indian J Urol 27(1):14–18PubMedPubMedCentralGoogle Scholar
  33. 33.
    Rahman MT, Mowladad C (2016) Zinc and benign prostatic hyperplasia (BPH) & prostate cancer (PCa) association. Med Res Arch 4:7Google Scholar
  34. 34.
    Franklin RB, Feng P, Milon B, Desouki MM, Singh KK, Kajdacsy-Balla A, Bagasra O, Costello LC (2005) hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Mol Cancer 4:32PubMedPubMedCentralGoogle Scholar
  35. 35.
    Henshall SM, Afar DE, Rasiah KK, Horvath LG, Gish K, Caras I (2003) Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer. Oncogene 22:6005–6012PubMedGoogle Scholar
  36. 36.
    Huang L, Kirschke CP, Zhang Y (2006) Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a possible role in prostate cancer progression. Cancer Cell Int 6:10PubMedPubMedCentralGoogle Scholar
  37. 37.
    Kashemsanta MCL, Suvatabandhu K, Airy SHK (1952) A new species of Pueraria (Leguminosae) from Thailand, yielding an oestrogenic principle. Kew Bull 7:263–266Google Scholar
  38. 38.
    Chansakaow S, Ishikawa T, Sekine K, Okada M, Higuchi Y (2000) Isoflavonoids from Pueraria mirifica and their estrogenic activity. Plant Med 66:572–575Google Scholar
  39. 39.
    Chansakaow S, Ishikawa T, Seki H, Sekine K, Okada M (2000) Identification of deoxymiroestrol as the actual rejuvenating principle of “Kwao Keur”, Pueraria mirifica. The known miroestrol may be an artefact. J Nat Prod 63:173–175PubMedGoogle Scholar
  40. 40.
    Cherdshewasart W, Panriansaen R, Picha P (2007) Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta. Maturitas 58(2):174–181PubMedGoogle Scholar
  41. 41.
    Urasopon N, Hamada Y, Asaoka K, Cherdshewasart W, Malaivijitnond M (2007) Pueraria mirifica, a phytoestrogen-rich herb, prevents bone loss in orchidectomized rats. Maturitas 56:322–331PubMedGoogle Scholar
  42. 42.
    Malaivijitnond SH, Cherdshewasart W, Watanabe G, Taya K (2007) The influence of Pueraria mirifica herb containing phytoestrogens on the urinarygonadotropin and estradiol levels in aged menopausal monkeys. Anim Sci J 78(4):378–386Google Scholar
  43. 43.
    Cherdshewasart W, Subtang S, Dahlan W (2007) Major isoflavonoid contents of the phytoestrogen rich-herb Pueraria mirifica in comparison with Pueraria lobata. J Pharmacol Biomed Anal 43:428–434Google Scholar
  44. 44.
    Turner JV, Snezana AK, Beverley DG (2007) Molecular aspects of phytoestrogen selective binding of estrogen receptors. J Pharm Sci 96(8):1879–1885PubMedGoogle Scholar
  45. 45.
    Härkönen PL, Mäkelä SI (2004) Role of estrogens in development of prostate cancer. J Steroid Biochem Mol Biol 92(4):297–305PubMedGoogle Scholar
  46. 46.
    Soronen P, Laiti M, Törn S, Härkönen P, Patrikainen L (2004) Sex steroid hormone metabolism and prostate cancer. J Steroid Biochem Mol Biol 92(4):281–286PubMedGoogle Scholar
  47. 47.
    Feng Y, Xia XY, Huang YF (2007) Effects of phytoestrogens on prostate cancer and benign prostatic hyperplasia. Zhonghua Nan Ke Xue 13(5):57–61Google Scholar
  48. 48.
    Masrudin SS, Mohamad J (2015) Preventive effect of Pueraria mirifica on testosteroneinduced prostatic hyperplasia in sprague dawley rats. Andrologia 47:1153–1159PubMedGoogle Scholar
  49. 49.
    Singleton VL, Rossi JAJ (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. J Enol Vitic 16:144–158Google Scholar
  50. 50.
    Chang ST, Wu JH, Wang SY, Kang PL, Yang NS (2001) Antioxidant activity of extracts from Acacia confusa bark and heartwood. J Agric Food Chem 49:3420–3424PubMedGoogle Scholar
  51. 51.
    Ablat A, Mohamad J, Awang K, Jamil AS, Aditya A (2014) Evaluation of antidiabetic and antioxidant properties of Brucea javanica seed. Sci World J.  https://doi.org/10.1155/2014/786130 Google Scholar
  52. 52.
    Müller L, Susanne G, Anne MP, Volker B (2010) Antioxidant capacity and related parameters of different fruit formulations. Food Sci Technol 43:992–999Google Scholar
  53. 53.
    OECD 423 (2001) OECD guidelines for testing of chemical acute oral toxicity-acute toxic class method adopted: 17th December 2001Google Scholar
  54. 54.
    Nahata A, Dixit VK (2012) Ganoderma lucidum is an inhibitor of testosteronw-induced prostatic hyperplasia in rats. Andrologia 44:160–174PubMedGoogle Scholar
  55. 55.
    O’Halloran J, Walsh AR, Fitzpatrick PJ, Christiansen N, Mathrani IM, Ahring BK (1998) The Determination of trace elements in biological and environmental samples using atomic absorption spectroscopy. In: Sheehan D, Totowa NJ (eds) Methods in biotechnology, Vol. 2. Humana Press, New York, pp 201–211Google Scholar
  56. 56.
    Cherdshewasart W, Sutjitb W (2008) Correlation of antioxidant activity and major isoflavonoid contents of the phytoestrogen-rich Pueraria mirifica and Pueraria lobata tubers. Phytomedicine 15:38–43PubMedGoogle Scholar
  57. 57.
    Buran P, Supan P (2007) Antioxidant capacities of Pueraria mirifica, Stevia rebaudiana Bertoni, Curcuma longa Linn., Andrographis paniculata (Burm.f.) Nees. and Cassia alata Linn. for the development of dietary supplement. Kasetsart J 41:548–554Google Scholar
  58. 58.
    Agraval M, Nahata A, Dixit VK (2012) Protective effects of Echinatus on testosterone-induced prostatic hyperplasia in rats. Eur J Integr Med 4:e177–e185Google Scholar
  59. 59.
    Huggins C, Hodges CV (1941) Studies on prostate cancer: effect of castration, of estrogen, and of androgen injection on serum phosphatase in metastatic carcinoma of the prostate. Cancer Res 1:293–297Google Scholar
  60. 60.
    Wang J, Isam-Eldin E, Lamartiniere CA (2002) Dietary genistein suppresses chemically induced prostate cancer in Lobund-Wistar rats. Cancer Lett 186:11–18PubMedGoogle Scholar
  61. 61.
    Khani B, Mehrabian F, Khalesi E, Eshraghi A (2011) Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome. J Res Med Sci 16(3):297–302PubMedPubMedCentralGoogle Scholar
  62. 62.
    Amani R, Zand-Moghaddam A, Jalali MT, Hatamizadeh MA (2002) Effects of soy protein isoflavones on lipid profile and serum hormones in hypercholesterolemic men. Biochem J 366(2):531–539Google Scholar
  63. 63.
    Kalo MS (2009) Effect of cholesterol biosynthesis inhibitor on some biochemical parameters in normal male rats. Iraqi J Vet Sci 23(1):5–12Google Scholar
  64. 64.
    Nica MB, Linda ED, Lisa JW, Jane YE, Murray WH (2002) Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem J 366:531–539Google Scholar
  65. 65.
    Andriolep GL, Humphrey P, Ray P, Gleave ME, Trachtenberg J, Thomas LN, Lazier CB, Rittmaster RS (2004) Effect of the dual 5α-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol 172(3):915–919Google Scholar
  66. 66.
    Bartsch G, Rittmaster RS, Klocker H (2002) Dihydrotestosterone and the concept of 5α-reductase inhibition in human benigh prostatic hyperplasia. World J Urol 19:413–425PubMedGoogle Scholar
  67. 67.
    Steers WD (2001) 5a-reductase activity in the prostate. Urology 58:17–24PubMedGoogle Scholar
  68. 68.
    Izumi AM, Wen-JyeLin, Kuo-PaoLai, Chawnshang C (2013) Androgen receptor roles in the development of benign prostate hyperplasia. Am J Pathol 182(6):1942–1949PubMedPubMedCentralGoogle Scholar
  69. 69.
    Suzuki S, Platz EA, Kawachi I (1992) Benign prostatic hyperplasia (BPH) is a common problem among older men. J Clin Endocrinol Metab 75:1022Google Scholar
  70. 70.
    Royuela M, de Miguel MP, Bethencourt FR, Sánchez-Chapado M, Fraile B, Arenas MI, Paniagua R (2001) Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate. J Endocrinol 168(3):447–454PubMedGoogle Scholar
  71. 71.
    Minutoli L, Altavilla D, Marini H, Rinaldi M, Irrer N, Pizzino G, Morgia G (2014) Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene. J Biomed Sci 21:19PubMedPubMedCentralGoogle Scholar
  72. 72.
    Rick FG, Schally AV, Block NL, Halmos G, Perez R, Fernandez JB, Vidaurre I, Szalontay L (2011) LHRH antagonist Cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia. Prostate 15(7):736–747Google Scholar
  73. 73.
    Costello LC, Franklin RB, Feng P, Tan M, Omar Bagasra (2005) Zinc and prostate cancer: a critical scientific, medical, and public interest issue (United States). Cancer Causes Control 16(8):901–915PubMedGoogle Scholar
  74. 74.
    Federico A, Lodice P, Federico P, Del Rio A, Mellone MC, Catalano G, Federico P (2001) Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract. Eur J Clin Nutr 55(4):293–297PubMedGoogle Scholar
  75. 75.
    Elzanaty S (2007) Association between age and epididymal and accessory sex gland function and their relation to sperm motility. Arch Androl 53:149–156PubMedGoogle Scholar
  76. 76.
    Chen QG, Zhang Z, Yang Q, Shan GY, Yu XY, Kong CZ (2012) The role of zinc transporter ZIP4 in prostate carcinoma. Urol Oncol 30(6):906–911PubMedGoogle Scholar
  77. 77.
    Christudoss P, Selvakumar R, Joseph FJ, Ganesh Gopalakrishnan (2011) Zinc status of patients with benign prostatic hyperplasia and prostate carcinoma. Indian J Urol 27(1):14–18PubMedPubMedCentralGoogle Scholar
  78. 78.
    Malm J, Hellman J, Hogg P, Lilia H (2000) Enzymatic action of prostate-specific antigen (PSA or hK3): substrate specificity and regulation by Zn (2+), a tight-binding inhibitor. Prostate 45(2):132–139PubMedGoogle Scholar
  79. 79.
    Michelle Y, Karin H, Emily H (2010) Differential response to zinc-induced apoptosis in benign prostate hyperplasia and prostate cancer cells. J Nutr Biochem 21:687–694Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Institute of Biological Sciences, Faculty of ScienceUniversity of MalayaKuala LumpurMalaysia
  2. 2.Human Anatomy Department, Faculty of Medicine and Health SciencesUniversity Putra MalaysiaSelangorMalaysia

Personalised recommendations