Biochemical and Histopathological evaluation of prostatic tissue under effect of Pterostilbene in benign prostatic hyperplasia rat model


  • Mohammed Ridha Jawad Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq
  • Ghaith Ali Jasim Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq



Benign prostatic hyperplasia, lower urinary tract symptoms,5α-reductase enzyme, Dihydrotestosterone, pterostilbene


Background: Benign prostatic hyperplasia [BPH] is the urologic condition that affects elderly men the most frequently Benign prostatic hyperplasia. Benign prostatic hyperplasia must be distinguished from

lower urinary tract symptoms and benign prostatic enlargement. which refers to an enlarged prostate, benign prostatic hyperplasia is a purely histological term the development, maintenance, and secretory activity of the prostate and other sex-accessory tissues are stimulated by the presence of certain hormones and growth factors. the pathophysiology of Benign prostatic hyperplasia is significantly influenced by the activity of the enzyme 5α-reductase. It's important to remember that 5-αreductase is responsible for creating Dihydrotestosterone a stronger androgen. Pterostilbene Mostly found in blueberries and grapes and pterostilbene substance with a number of biological properties including anticancer properties. pterostilbene is a lipid-soluble molecule that exists in both cis and trans forms with the latter being more prevalent. The conventional medication for Benign prostatic hyperplasia utilized in this trial was finasteride which inhibits the 5α-reductase enzyme and lowers the amount of Dihydrotestosterone.

Methods: Forty-eight male rats were divided into six groups; the control group consisted of eight rats who received subcutaneous injections of oil vehicle for a period of 42 days. The induction group consisted of eight rats who received subcutaneous injections of testosterone propionate for a period of fourteen days. The finasteride group consisted of eight rats who received finasteride 0.44 mg/kg by oral gavage for a period of twenty-eight days following the induction of Benign prostatic hyperplasia and Pterostilbene 200 group included 8 rats were given pterostilbene 200mg/kg by oral gavage for 28 days after 14 days of Benign prostatic hyperplasia induction. pterostilbene 100 group included 8 rats were given a pterostilbene 100mg/kg per day kg by oral gavage for 28 days after 14 days of induction Benign prostatic hyperplasia dose and the resveratrol group included 8 rats were given a resveratrol 100mg/kg per day kg by oral gavage for 28 days after 14 days of induction Benign prostatic hyperplasia After twenty-eight days.

Results: Histological section of prostate Pterostilbene 200 were similar those in control negative revealed numerous variable sizes alveoli that filled with homogenous eosinophilic secretion, had normal epithelial and stromal tissue.

Conclusion: Pterostilbene have a potent anti-proliferative effect by decrease the hyperplastic nodules for prostate and return epithelial cell to normal and have a very good scavenging activity for free radical [very good as antioxidant] in compare with Vitamin c and resveratrol.

Aim of study: evaluate the effect of Pterostilbene as Anti proliferative on Benign prostatic hyperplasia and assess the antioxidant activity for Pterostilbene by DPPH Assay.


- Madersbacher S, Sampson N, Culig Z. Pathophysiology of Benign Prostatic Hyperplasia and Benign Prostatic Enlargement: A Mini-Review. Gerontology 2019;65[5]:458–64.

- Foo KT. Pathophysiology of clinical benign prostatic hyperplasia. Asian J Urol [Internet] 2017;4[3]:152–7. Available from: /10.1016/j.ajur.2017.06.003

- Article R. Pathophysiology of benign prostate enlargement and lower urinary tract symptoms: Current concepts. 2017;29[2]:79–83.

- Phua TJ. The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective. Medicines 2021;8[6]:30.

- Wang R, Xu Z, Tian J, Liu Q, Dong J, Guo L, Hai B, Liu X, Yao H, Chen Z, Xu J. Pterostilbene inhibits hepato-cellular carcinoma proliferation and HBV replication by targeting ribonucleotide reductase M2 protein. American journal of cancer research. 2021;11[6]:2975.

- Nagarajan S, Mohandas S, Ganesan K, Xu B, Ramkumar KM. New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects. Mol 2022, Vol 27, Page 6316 2022;27[19]:6316.

- Sirerol JA, Rodríguez ML, Mena S, Asensi MA, Estrela JM, Ortega AL. Role of natural stilbenes in the prevention of cancer. Oxidative Medicine and Cellular Longevity. 2016 Oct;2016.

- Obrador E, Salvador-Palmer R, Jihad-Jebbar A, López-Blanch R, Dellinger TH, Dellinger RW, Estrela JM. Pterostilbene in cancer therapy. Antioxidants. 2021 Mar 21;10[3]:492.

- Yeo SCM, Ho PC, Lin HS. Pharmacokinetics of pterostilbene in Sprague-Dawley rats: The impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability. Mol Nutr Food Res 2013;57[6]:1015–25.

- Wang P, Sang S. Metabolism and pharmacokinetics of resveratrol and pterostilbene. BioFactors. 2018 Jan;44[1]:16-25.

- Kumara P, Sunil K, Arun Kumar B. Determination of DPPH free radical scavenging activity by RP-HPLC, rapid sensitive method for the screening of berry fruit juice freezes dried extract. Natural Products Chemistry & Research. 2018;6[5]:1-7.

- Kang DW, Ryu CH, Kim JH, Choi GW, Kim S, Chon CH, Cho HY. Pharmacokinetic-pharmacodynamic modeling approach for dose prediction of the optimal long-acting injectable formulation of finasteride. International Journal of Pharma-ceutics. 2021 May 15; 601 :120527.

- dos Santos Lacerda D, Türck P, Gazzi de Lima‐Seolin B, Colombo R, Duarte Ortiz V, Poletto Bonetto JH, Campos‐Carraro C, Bianchi SE, Belló‐Klein A, Linck Bassani V, Sander da Rosa Araujo A. Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves systolic function of right ventricle in cor pulmonale model. British Journal of Pharmacology. 2017 Oct;174[19] :3302-14.

- Cai H, Scott EN, Britton RG, Parrott E, Ognibene TJ, Malfatti M, et al. Distribution and metabolism of [14C]-resveratrol in human prostate tissue after oral administration of a “dietary-achievable” or “pharmacological” dose: What are the implications for anticancer activity? Am J Clin Nutr 2021;113[5]:1115–25.

- Siddiqui MA, Asad M, Akhter J, Hoda U, Rastogi S, Arora I, Aggarwal NB, Samim M. Resveratrol-Loaded Glutathione-Coated Collagen Nano-particles Attenuate Acute Seizures by Inhibiting HMGB1 and TLR-4 in the Hippocampus of Mice. ACS Chemical Neuroscience. 2022 Apr 6;13[8] :1342-54.

- Obisike UA, Nwachuku EO, Boisa N, Nduka N. Determination of exogenous testosterone propionate dose for induction of benign prostatic hyperplasia in rat model. European Journal of Biomedical and Pharmaceutical Sciences. 2019;6[13] :141-47.

- Gupta AK, Venkataraman M, Talukder M, Bamimore MA. Finasteride for hair loss: a review. J Dermatolog Treat 2022;33[4]:1938–46.

- Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy. 2016 Mar;7[2]:27.

- Zhang Y, Li Y, Sun C, Chen X, Han L, Wang T, Liu J, Chen X, Zhao D. Effect of pterostilbene, a natural derivative of resveratrol, in the treatment of colorectal cancer through Top1/Tdp1-mediated DNA repair pathway. Cancers. 2021 Aug 9;13[16]:4002.

- Guo L, Tan K, Wang H, Zhang X. Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis. Oncology Reports. 2016 Dec 1;36[6]:3233-40.

- Mitsunari K, Miyata Y, Matsuo T, Mukae Y, Otsubo A, Harada J, et al. Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia. Mol 2021, Vol 26, Page 450 2021;26 [2]:450.

- Chung KS, Cheon SY, An HJ. Effects of resveratrol on benign prostatic hyperplasia by the regulation of inflammatory and apoptotic proteins. Journal of Natural Products. 2015 Apr 24;78[4]:689-94.

- Struck MB, Andrutis KA, Ramirez HE, Battles AH. Effect of a short-term fast on ketamine–xylazine anesthesia in rats. Journal of the American Association for Laboratory Animal Science. 2011 May 15;50[3]:344-8.

- Ateyah MA, Abdulridha MK, Alkabee MJ. Effects of Saw Palmetto Therapy on some Inflammatory Biomarkers in a Sample of Iraqi Male with Symptomatic Benign Prostatic Hyperplasia. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2021;21 [1]:1-9.

- Slaoui M, Fiette L. Histopathology procedures: from tissue sampling to histopathological evaluation. Methods Mol Biol 2011; 691:69–82.

- Cai H, Zhang G, Yan Z, Shang X. The Effect of Xialiqi Capsule on Testosterone-Induced Benign Prostatic Hyperplasia in Rats. Evid Based Complement Alternat Med [Internet] 2018 [cited 2022 Jul 7];2018. Available from: /pmc/ articles/PMC6186362/

- Qasim LB, Jasim GA, Rabeea IS. Histopathological study of diclofenac induced acute renal failure under lipoic acid and bosentan therapy in male albino rats. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2022 Jul 4;22[1]:49-58.

- Ficarra V. Is chronic prostatic inflammation a new target in the medical therapy of lower urinary tract symptoms [LUTS] due to benign prostate hyperplasia [BPH]? BJU international. 2013 Aug;112[4]:421-2.

- Nickel JC. Inflammation and benign prostatic hyperplasia. Urologic Clinics of North America. 2008 Feb 1;35[1]:109-15.

- Gandaglia G, Briganti A, Gontero P, Mondaini N, Novara G, Salonia A, Sciarra A, Montorsi F. The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia [BPH]. BJU international. 2013 Apr 12;112 [4]:432-41.

- Wang TTY, Schoene NW, Kim YS, Mizuno CS, Rimando AM. Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Mol Nutr Food Res 2010;54[3]:335–44.

- McCormack D, McFadden D. A review of pterostilbene antioxidant activity and disease modification. Oxidative medicine and cellular longevity. 2013 Oct;2013.

- Chakraborti S, editor. Handbook of Oxidative Stress in Cancer: Therapeutic Aspects. Springer Nature; 2022 Sep 28.

- Ejike CE, Ezeanyika LU. Management of experimental benign prostatic hyperplasia in rats using a food-based therapy containing Telfairia occidentalis seeds. African Journal of Traditional, Complem-entary and Alternative Medicines. 2011;8[4].

- Mccormick DL, Kapetanovic IM, Muzzio M, Huang Z, Thompson TN, Mccormick DL. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol 2011;68[3]:593–601.

- Bishayee A. Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical TrialsResveratrol and Cancer: In Vivo and Clinical Studies. Cancer prevention research. 2009 May 1;2 [5]:409-18.

- Cinislioglu AE, Demirdogen SO, Cinislioglu N, Altay MS, Sam E, Akkas F, et al. Variation of Serum PSA Levels in COVID-19 Infected Male Patients with Benign Prostatic Hyperplasia [BPH]: A Prospective Cohort Studys. Urology 2022; 159:16–21.

- Ejike CECC, Ezeanyika LUS. Management of experimental benign prostatic hyperplasia in rats using a food-based therapy containing Telfairia occidentalis seeds. African J Tradit Complement Altern Med 2011 ;8[4]:398–404.

- Gao Y, He C, Ran R, Zhang D, Li D, Xiao PG, et al. The resveratrol oligomers, cis- and trans-gnetin H, from Paeonia suffruticosa seeds inhibit the growth of several human cancer cell lines. J Ethnopharmacol 2015; 169:24–33.

- Mbaka G, Anunobi C, Ogunsina S, Osiagwu D. Histomorphological changes in induced benign prostatic hyperplasia with exogenous testosterone and estradiol in adult male rats treated with aqueous ethanol extract of Secamone afzelii. Egyptian Journal of Basic and Applied Sciences. 2017 Mar 1;4[1]:15-21.

- Li Y, Ma J, Qin XH, Hu CY. The efficacy and safety of dutasteride and finasteride in patients with benign prostatic hyperplasia: a systematic review and meta-analysis. Translational Andrology and Urology. 2022 Mar;11[3]:313.

- Golchin-Rad K, Mogheiseh A, Nazifi S, Ahrari Khafi MS, Derakhshandeh N, Abbaszadeh-Hasiri M. Changes in the Serum Prostatic Biomarkers During the Treatment of Benign Prostatic Hyperplasia with a 5alpha-reductase Inhibitor: Finasteride. Top Companion Anim Med 2020; 38:100405.

- Mahmood Yaseen S, Al-Samarai FR, Hasan HF. How to Cite: Histopathological and reproductive effect of tamsulosin and finasteride on induced Benign prostate hyperplasia in mice. 607626085 Int J Heal Sci 2022;6[S1].

- Li C, Hu WL, Lu MX, Xiao GF. Resveratrol induces apoptosis of benign prostatic hyperplasia epithelial cell line [BPH-1] through p38 MAPK-FOXO3a pathway. BMC Complement Altern Med 2019;19[1]:1–7.

- Lee G, Shin J, Choi H, Jo A, Pan S, Bae D, et al. Cynanchum wilfordii ameliorates testosterone-induced benign prostatic hyperplasia by regulating 5α-reductase and androgen receptor activities in a rat model. Nutrients 2017;9[10].

- Gao H, Liu Z, Xu W, Wang Q, Zhang C, Ding Y, et al. Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells. Sci Reports | 123AD; 11:6381.

- Semenov AL, Gubareva EA, Ermakova ED, Dorofeeva AA, Tumanyan IA, Radetskaya EA, Yurova MN, Aboushanab SA, Kanwugu ON, Fedoros EI, Panchenko AV. Astaxantin and Isoflavones inhibit benign prostatic hyperplasia in rats by reducing oxidative stress and normalizing Ca/Mg balance. Plants. 2021 Dec 12;10[12]:2735.

- Pyo KH, Lee YW, Lee SH, Xin CF, Shin JH, Shin EH. Preventive effects of resveratrol-enriched extract of peanut sprout on bacteria-and estradiol-induced prostatitis in mice. Natural Product Communications. 2017Jan;12[1]:1934578X1701200120

- Sciarra A, Di Silverio F, Salciccia S, Autran Gomez AM, Gentilucci A, Gentile V. Inflammation and Chronic Prostatic Diseases: Evidence for a Link? Eur Urol 2007;52[4]:964–72.

- Tse BWC, Scott KF, Russell PJ. Paradoxical Roles of Tumour Necrosis Factor-Alpha in Prostate Cancer Biology. Prostate Cancer 2012; 2012:1–8.

- Zachara BA, Szewczyk-Golec K, Tyloch J, Wolski Z, Szylberg T, Stepien S, Kwiatkowski S, Bloch-Boguslawska E, Wasowicz W. Blood and tissue selenium concentrations and glutathione peroxidase activities in patients with prostate cancer and benign prostate hyperplasia. Neoplasma. 2005 Jan 1;52[3]:248-54.

- Ahmad M, Suhail N, Mansoor T, Banu N, Ahmad S. Evaluation of oxidative stress and DNA damage in benign prostatic hyperplasia patients and comparison with controls. Indian Journal of Clinical Biochemistry. 2012 Oct;27[4]:385-8.

- Sinisi AA, Pasquali D, Notaro A, Bellastella A. Sexual differentiation. J Endocrinol Invest 2003;26[3 Suppl] :23–8.