CC BY-NC-ND 4.0 · Planta Medica International Open 2022; 9(01): e90-e107
DOI: 10.1055/a-1729-3499
Original Papers

Biochemical Characterization of the Pharmacological Effects of Yagari in Experimentally Induced Benign Prostatic Hyperplasia

Uzuazokaro Mark-Maria Agatemor
1   Support Office, Boots UK, Nottingham, United Kingdom
Okwesili Fred Chiligue Nwodo
2   Department of Biochemistry, University of Nigeria, Nsukka, Nigeria
› Author Affiliations


Benign prostatic hyperplasia is a progressive pathologic condition common in ageing men, constituting a health burden. Benign prostatic hyperplasia is characterized by the proliferation of prostatic tissues, prostate enlargement, and lower urinary tract symptoms. The use of herbal medicine in the management and treatment of benign prostatic hyperplasia has shown some promise. The efficacy and potency of some polyherbal extracts have been scientifically proven in the management and treatment of diseases, while many others are yet to be investigated. The aim of this study was to determine the effect of the herbal mixture Yagari on experimentally induced benign prostatic hyperplasia in rats and to identify its pharmacologically active agents. The effect of the herbal mixture on experimentally induced benign prostatic hyperplasia in rats was determined using 36 male Wistar rats grouped randomly into 6 groups of 6 rats each. The test rats were treated subcutaneously using a combination of dihydrotestosterone and estradiol valerate in a 10:1 ratio for 28 days according to the standard method. The test rats were thereafter treated with the herbal mixture for 21 days. Prostate-specific antigen, inflammatory cytokines, assay of prostate function hormonal and prostate function enzyme activities, and kidney function test were evaluated in the blood samples collected by ocular puncture applying standard methods. Prostates were harvested and examined for histopathological changes. Biological activity-guided fractionation of Yagari in a silica gel column was carried out and using phospholipase A2 activity as a biomarker. The identity of the bioactive compounds was determined using mass spectroscopy and nuclear magnetic resonance. The herbal mixture showed a positive effect on prostatic hyperplasia by decreasing urinary obstruction through the inhibition of 5-alpha reductase, anti-inflammatory activity, and decreased level of sex hormones. Characterization by spectral studies revealed apigenin (4´,5,7-trihydroxyflavone, molecular weight).

Supplementary Material

Publication History

Received: 18 April 2021
Received: 30 November 2021

Accepted: 22 December 2021

Article published online:
19 March 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Mehik A, Hellstrom P, Sarpola A, Lukkarinen O, Jarvelin MR. Fears, sexual disturbance and personality features in men with prostatitis: a population-based cross-sectional study in Finland. BJU International 2001; 88: 35-38
  • 2 Ezeanyika LUS, Ejike ECCC, Obidoa O, Elom SO. Prostate disorders in an apparently normal Nigerian population 1: Prevalence. Biokemistri 2006; 18: 127-132
  • 3 Bostwick DG, Kirby RS, McConnell JD, Fitzpatrick JM, Roehrborn CG, Boyle P. The pathology of benign prostatic hyperplasia: textbook of benign prostatic hyperplasia. London: Isis Medical Media; 2002. 432.
  • 4 Rył A, Rotter I, Słojewski M, Jędrzychowska A, Marcinowska Z, Grabowska M and Laszczyńska M. Can metabolic disorders in aging men contribute to prostatic hyperplasia eligible for transurethral resection of the prostate (TURP)? Int J Environ Res Public Health 2015; 12: 3327–3342
  • 5 Jiao Y, Wang L, Gu X, Tao S, Tian L, Na R, Chen Z, Kang J, Zheng SL, Xu J, Sun J and Qi J (2013). LILRA3 is associated with benign prostate hyperplasia risk in a chinese population. International Journal of Molecular Science, 14 (5): 8832–8840.
  • 6 Chughtai B, Lee R, Te A, Kaplan S. Role of inflammation in benign prostatic hyperplasia. Rev Urol 2011; 13: 147-150
  • 7 Sausville J, Naslund M. Benign prostatic hyperplasia and prostate cancer: an overview for primary care physicians. Int J Clin Pract 2010; 64: 1740-1745
  • 8 Gat Y, Gornish M, Heiblum M, Joshua S. Reversal of benign prostate hyperplasia by selective occlusion of impaired venous drainage in the male reproductive system: novel mechanism, new treatment. Andrologia 2008; 40: 273-281
  • 9 Wang JY, Liu M, Zhang YG, Zeng P, Ding Q, Huang J, He DL, Song B, Kong CZ and Pang J. Relationship between lower urinary tract symptoms and objective measures of benign prostatic hyperplasia: A Chinese survey. Chinese Medical Journal (English) 2008; 121: 2042–2045
  • 10 Nahata A, Dixit VK. Ameliorative effects of stinging nettle (Urticadioica) on testosterone-induced prostatic hyperplasia in rats. Andrologia 2011; 20: 1-14
  • 11 Kao CL, Hsieh CJ, Chen CY, Liu CM. The pharmacological effects of natural products and herbs in benign prostatic hyperplasia. Austin J Nutri. Food Sci 2014; 2: 1054-1057
  • 12 Nwodo OFC, Omeje KO. Personal communication on herbal mixtures for BPH treatment at Nsukka, Enugu State, Nigeria; 2016
  • 13 Ejike CECC, Ezeanyika LUS. Management of experimental benign prostatic hyperplasia in rats using a food-based therapy containing Telfairia occidentalis seeds. Afr J Tradit Complement Altern Med 2011; 8: 398-404
  • 14 Jeyaraj DA, Uduyakumar TS, Rajalakshmi M, Pal PC, Sharma RS. Effects of long-term administration of androgens and estrogen on rhesus monkey prostate: possible induction of benign prostatic hyperplasia. J Androl 2000; 21: 833-841
  • 15 Nandecha C, Nahata A, Dixit VK. Effect of Benincasa hispida fruits on testosterone-induced prostatic hypertrophy in albino rats. Curr Ther Res 2010; 71: 331-343
  • 16 Ejike CECC, Ezeanyika LUS.. Inhibition of the experimental induction of benign prostatic hyperplasia: a possible role for fluted pumpkin (Telfairia occidentalis Hook f.) seeds. Urol Int 2011; 87: 218-224
  • 17 Fawcett JK, Scott JE. Spectrophotometric determination of urea in human serum. J Clin Pathol 1960; 13: 156-162
  • 18 Henry JB. Clinical diagnosis and management by laboratory methods, 22nd Edition. Philadelphia: W.B. Saunders; 1984. 1434.
  • 19 Ismail AAA, Niswender GD, Midgley AR. Radioimmunoassay of testosterone without chromatography. J Clin Endocrinol 1972; 34: 117-121
  • 20 Bassett RM. A simple chromatographic method for the radioimmunoassay of four androgenic steroids. Med Lab Sci 1980; 37: 31-45
  • 21 Gutman AB, Gutman EB. An acid phosphatase occurring in the serum of patients with metastasizing carcinoma of the prostate gland. J Clin Investig 1938; 17: 473-478
  • 22 Gupta AK, Holzgreve W, Hahn W. Microparticle-free placentally derived soluble factors down-modulate the response of activated T cells. Hum Immunol 2005; 66: 977-984
  • 23 Bonavida B. Immunomodulatory effect of tumor necrosis factor. Biotherapy 1991; 3: 127-133
  • 24 Stowell L, Sharman I, Hamel K. An enzyme-linked immunosorbent assay (ELISA) for prostate specific antigen. For Sci Intern 1991; 50: 125-138
  • 25 Johnsen I, Eliasson R. Evaluation of a commercially available kit for the colorimetric determination of zinc. Int J Androl 1987; 10: 435-440
  • 26 Culling CFA. Handbook of histopathological and histochemical techniques, 3rd Edition. London: Butterworth-Heinemann; 1975. 26.
  • 27 Ramani YR, Panigrahy B, Sahu SR, Mishra SK. Effect of Mentha piperata in experimental prostatic hyperplasia in Wistar albino rats. Int J Pharm Sci 2015; 7: 192-194
  • 28 Kim Y, Kim M, Chun S, Choi J. Effect of Phellius linteus water extract on benign prostatic hyperplasia. Nutr Res Pract 2013; 7: 172-177
  • 29 Pais P. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II. Adv Ther 2010; 27: 555-563
  • 30 El Shoubaky GA, Abdel-Daim MM, Mansouri MH, Salem EA. Isolation and identification of a flavone apigenin from marine red alga Acanthophora spicifera with antinociceptive and anti-Inflammatory activities. J Exp Neurosci 2016; 10: 21-29
  • 31 Veeresh-Babu SV, Veeresh B, Patil AA, Warke YB. Lauric acid and myristic acid prevent testosterone induced prostatic hyperplasia in rats. Eur J Pharmacol 2010; 626: 262-265
  • 32 Yang BC, Jin LL, Yang YF, Li K, Peng DM. Inhibitory effect of rape pollen supercritical CO2 fluid extract against testosterone-induced benign prostatic hyperplasia in rats. Exp Ther Med 2014; 8: 31-37
  • 33 Yang X, Yuan L, Xiong C, Yin C, Ruan J. Abacopteris penangiana exerts testosterone-induced benign prostatic hyperplasia protective effect through regulating inflammatory responses, reducing oxidative stress and anti-proliferative. J Ethnopharmacol 2014; 157: 105-113
  • 34 Woo-Young J, Ohn SK, Chang-Seob S, Seong EJ, Jung-Ae K, Hyeun-Kyoo S. Yong-ung K and Mee-Young L. Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats. BMC Complement. Altern Med 2017; 17: 384-391
  • 35 Tsai PJ, Lin JT, Wu TT, Tsai CC. Ureterosciatic hernia causes obstructive uropathy. J Chin Med Assoc 2008; 71: 491-493
  • 36 Homma Y, Gotoh M, Yokoyama O, Masumori N, Kawauchi A, Yamanishi T. Ishizuka, O, Seki N, Kamoto T, Nagai A, Ozono S and Japanese Urological Association. Outline of JUA clinical guidelines for benign prostatic hyperplasia. Int J Urol 2011; 18: 741-756
  • 37 Reynolds AC, Dorrian J, Liu PY, Ramdongen HP, Wittert GA, Harmer LJ. and Banks S. Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men. PLoS One 2012; 7: 412-418
  • 38 Muniyan A, Chaturvedi NK, Dwyer JG, LaGrange CA, Chaney WG, Ming-Fong L. Human prostatic acid phosphatase: structure, function and regulation. Int J Mol Sci 2013; 14: 10438-10464
  • 39 Atsushi I, Yoshimura T, Wada K, Watabe S, Yuki Sakamoto Y, Ito E. Miura, T. Spectrophotometric method for the assay of steroid 5-alpha reductase activity of rats liver and prostate microsomes. Anal Sci 2013; 29: 455-459
  • 40 Jebor MA, Abood MRK, Lilo RA. Biochemical changes in patients with benign prostate hyperplasia. JUBPAS 2014; 22: 1-7
  • 41 Mishra VC, Allen DJ, Nicolaou C, Sharif H, Hudd C, Karim OM. Does intraprostatic inflammation have a role in the pathogenesis and progression of benign prostatic hyperplasia?. BJU Int 2007; 100: 327-331
  • 42 Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer 2001; 1: 34-45
  • 43 Morote J, Ramirez C, Gomez E, Planas J, Raventos CX, De Torres IM. Catalan R. The relationship between total and free serum testosterone and the risk of prostate cancer and tumor aggressiveness. BJU Int 2009; 104: 486-489
  • 44 Lee MY, Shin IS, Seo CS, Lee NH, Ha HK, Son JK. and Shin HK Effects of Melandrium firmum methanol extract on testosterone-induced benign prostatic hyperplasia in Wistar rats. Asian J Androl 2012; 14: 320-324
  • 45 Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 2006; 175: 1422-1426
  • 46 Nickel JC, Roehrborn CG, O’Leary MP, Bostwick DG, Somerville MC, Rittmaster RS. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the reduce trial. Eur Urol 2008; 54: 1379-1384
  • 47 Penna G, Fibbi B, Amuchastegui S, Cossetti C, Aquilano F, Laverny G. Gacci M, Crescioli C, Maggi M and Adorni L Chronic immune-mediated inflammation stromal cells as inducers and targets of human benign prostatic hyperplasia. J Immunol 2009; 182: 27-31
  • 48 Cosimo D N, Gero K, Michael M, Rodolfo M, William N, Fritz S, Alessandro S and Andrea T. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol 2011; 60: 106–117
  • 49 Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 2007; 96: 41-101
  • 50 Steiner GE, Stix U, Handisurya A. Cytokine expression pattern in benign prostatic hyperplasia infiltrating T-cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue. Lab Invest 2003; 83: 1131-1146
  • 51 Comalada M, Ballester L, Bailon E, Sierra S, Xaus J, Galvez J. de Medina, FS and Zarzuelo A. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Biochem Pharmacol 2006; 72: 1010-1021
  • 52 Park SG, Choi HC, Cho B, Kwon YM, Kwon MT, Park JH. Effect of central obesity on prostate-specific antigen measured by computerized topography: related markers and prostate volume. J Urol 2012; 187: 1589-1593
  • 53 Balk SP, Ko YJ, Bubley GJ. Biology of prostate specific antigen. J Clin Oncol 2003; 21: 383-391
  • 54 Zhang X, Wang G, Gurley EC, Zhou H. Flavonoid apigenin inhibits lipopolysaccharide-Induced inflammatory response through multiple mechanisms in macrophages. PLoS One 2014; 9: 72-90
  • 55 Mbaka GO, Ogbonnis SO, Olarewaju OT, Duru FI. The effects of ethanol seed extract of Raphia hookeri on exogenous testosterone and estradiol induced benign prostatic hyperplasia in adult male rats. J Morphol Sci 2013; 30: 235-243
  • 56 Park SY, Wilkens LR, Morris JS, Henderson BE, Kolonel LN. Serum zinc and prostate cancer risk in a nested case-control study: The multiethnic cohort. Prostate 2013; 73: 261-266
  • 57 Gonzales C, Leiva R, Rubio J, Gasco M, Gonzales GF. Effect of red maca (Lepidium meyenii) on prostate and serum zinc levels in rats with testosterone-induced prostatic hyperplasia. Int J Androl 2012; 44: 362-370
  • 58 Widyawati PS, Budianta TDW, Kusuma FA, Wijaya EL. Difference of solvent polarity to phytochemical content and antioxidant activity of Pluchea indicia less leaves extracts. Int J Pharmacog Phytochem Res 2015; 6: 850-855
  • 59 Yu Lin H, Kuo YH, Lin YL, Chiang W. Antioxidative effect and active component from leaves of lotus (Nelumbo nucifera). J Agric Food Chem 2009; 57: 6623-6629
  • 60 Dehkharghanian M, Adenier H, Vijayalakshmi MA. Analytical methods study of flavonoids in aqueous spinach extract using positive electrospray ionisation tandem quadrupole mass spectrometry. Food Chem 2010; 121: 863-870
  • 61 Abarca-Vargas R, Malacara CFP, Petricevich VL. Characterization of Chemical Compounds with Antioxidant and Cytotoxic Activities in Bougainvillea x buttiana Holttum and Standl, (var. Rose) Extracts. Antioxidant 2016; 5: 45-56
  • 62 Rajeshwari HP, Babu RL, Naveen Kumar M, Kiran Kumar KM, Hegde SM, Nagesh R, Ramesh GT, Sharma SC. Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells. Inflammation 2016; 39: 138-147
  • 63 Sawatzky D, Willoughby D, Colville-Nash P, Rossi A. The involvement of the apoptosis-modulating proteins Erk 1/2, Bcl-xL, and Bax in the resolution of acute inflammation in vivo . Am J Pathol 2006; 168: 33-41
  • 64 Sarian M N, Ahmed Q U, Mat So’ad S Z, Alhassan M A, Murugesu S, Perumal V, Syed Mohamad SNA, Khatib A and Latip J.Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study. Biomed Res Int 2017; 17: 1–14
  • 65 Liang H, Sonego S, Gyengesi E, Rangel A, Niedermayer G, Karl T. and Munch G. Anti-inflammatory and neuroprotective effect of apigenin: studies in the GFAP-IL6 mouse model of chronic neuroinflammation. Free Rad Biol Med 2017; 108: S10-S15
  • 66 Mak P, Leung YK, Tang WY, Harwood C, Ho SM. Apigenin suppresses cancer cell growth through ERbeta. Neoplasia 2006; 8: 896-904
  • 67 Bektic J, Guggenberger R, Spengler B, Christoffel V, Pelzer A, Ramoner, R and Klocker H. The flavonoid apigenin inhibits the proliferation of prostatic stromal cells via the MAPK-pathway and cell-cycle arrest in G1/S. Maturitas 2006; 55: 37–46
  • 68 Harborne JB. Phytochemical methods: a guide to modern technology of plant analysis, 3rd Edition. New York: Chapman and Hall; 1998: 88-185
  • 69 AOAC. Official methods of analysis of the association of analytical chemists, 16th Edition. Washington D.C.: AOAC International ; 2000: 12-13
  • 70 Trease GE, Evans MC. Textbook of pharmacognosy, 15th Edition. London: Saunder Publishers; 2002: 342-393
  • 71 Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983; 55: 275-287