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Inhibitory effects of Hydrocotyle ramiflora on testosterone-induced benign prostatic hyperplasia in rats

  • Urology - Original Paper
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Abstract

Purpose

Benign prostatic hyperplasia (BPH) is a urogenital disorder that affects approximately 85% of males who are over 50 years of age. Hydrocotyle ramiflora (HR), belonging to Apiaceae family, is used to treat urinary system diseases such as urine retention in traditional Chinese herbal medicine. In this study, we evaluated the effects of HR in the BPH animal model.

Methods

We induced BPH in rats via subcutaneous (sc) injections of testosterone propionate (TP, 3 mg/kg). Rats were also administered HR (150 mg/kg), finasteride (10 mg/kg), or vehicle via oral gavage. After induction, prostate glands were collected, weighed, and processed for further analysis, including histopathological examination and immunohistochemistry. In addition, the mRNA expression of inflammatory cytokines in prostatic tissues was determined by quantitative real-time PCR (qRT-PCR). The protein expression of pro-apoptotic markers was examined using western blotting.

Results

HR treatment significantly reduced the prostate weight, epithelial thickness, and proliferating cell nuclear antigen (PCNA) expression, with the levels of cleaved caspase-3 and Bcl-2-associated X (Bax) protein considerably increased compared to BPH group. HR also decreased inflammatory cell infiltration and pro-inflammatory cytokine levels compared with BPH group. Furthermore, the expression of phosphor-nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were reduced by HR treatment.

Conclusion

These results indicate that HR suppresses the development of BPH associated with anti-proliferative, pro-apoptotic, and anti-inflammatory effects, suggesting it is a potential alternative therapeutic agent for BPH.

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Data availability statement

Not applicable.

References

  1. Minutoli L et al (2016) Apoptotic pathways linked to endocrine system as potential therapeutic targets for benign prostatic hyperplasia. Int J Mol Sci 17:1311. https://doi.org/10.3390/ijms17081311

    Article  CAS  Google Scholar 

  2. Abdelwahab O et al (2012) Evaluation of the resistive index of prostatic blood flow in benign prostatic hyperplasia. Int Braz J Urol 38:250–257. https://doi.org/10.1590/S1677-55382012000200014

    Article  Google Scholar 

  3. Patel ND, Parsons JK (2014) Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction. Indian J Urol 30:170–176. https://doi.org/10.4103/0970-1591.126900

    Article  Google Scholar 

  4. Ub Wijerathne C et al (2017) Quisqualis indica improves benign prostatic hyperplasia by regulating prostate cell proliferation and apoptosis. Biol Pharm Bull 40:2125–2133. https://doi.org/10.1248/bpb.b17-00468

    Article  Google Scholar 

  5. Izumi K et al (2013) Androgen receptor roles in the development of benign prostate hyperplasia. Am J Pathol 182:1942–1949. https://doi.org/10.1016/j.ajpath.2013.02.028

    Article  CAS  Google Scholar 

  6. Andriole G et al (2004) Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 172:1399–1403. https://doi.org/10.1097/01.ju.0000139539.94828.29

    Article  CAS  Google Scholar 

  7. Ishimaru T, Pages L, Horton R (1977) Altered metabolism of androgens in elderly men with benign prostatic hyperplasia. J Clin Endocrinol Metab 45:695–701. https://doi.org/10.1210/jcem-45-4-695

    Article  CAS  Google Scholar 

  8. Feldman HA et al (2002) Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 87:589–598. https://doi.org/10.1210/jcem.87.2.8201

    Article  CAS  Google Scholar 

  9. Liao CH et al (2012) Significant association between serum dihydrotestosterone level and prostate volume among Taiwanese men aged 40–79 years. Aging Male 15:28–33. https://doi.org/10.3109/13685538.2010.550660

    Article  CAS  Google Scholar 

  10. Gandaglia G et al (2013) The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int 112:432–441. https://doi.org/10.1111/bju.12118

    Article  Google Scholar 

  11. Bostanci Y et al (2013) Correlation between benign prostatic hyperplasia and inflammation. Curr Opin Urol 23:5–10. https://doi.org/10.1097/MOU.0b013e32835abd4a

    Article  Google Scholar 

  12. Ren H et al (2015) The effects of ROS in prostatic stromal cells under hypoxic environment. Aging Male 18:84–88. https://doi.org/10.3109/13685538.2015.1018159

    Article  CAS  Google Scholar 

  13. Verze P, Cai T, Lorenzetti S (2016) The role of the prostate in male fertility, health and disease. Nat Rev Urol 13:379–386. https://doi.org/10.1038/nrurol.2016.89

    Article  CAS  Google Scholar 

  14. Huang SS et al (2008) Antioxidant and antiproliferative activities of the four Hydrocotyle species from Taiwan. Bot Stud 49:311–322

    Google Scholar 

  15. Kwon HC, Zee OP, Lee KR (1998) Two new monogalactosylacylglycerols from Hydrocotyle ramiflora. Planta Med 64:477–479. https://doi.org/10.1055/s-2006-957491

    Article  CAS  Google Scholar 

  16. Yang JS et al (2007) Effect of alpha-spinasterol extracted from Phytolacca americanna on the apoptosis of U937 cell line. J Physiol Pathol Korean Med 21:1108–1117

    Google Scholar 

  17. Jeong SI et al (2004) Alpha-spinasterol isolated from the root of Phytolacca americana and its pharmacological property on diabetic nephropathy. Planta Med 70:736–739. https://doi.org/10.1055/s-2004-827204

    Article  CAS  Google Scholar 

  18. Borges FR et al (2014) Anti-inflammatory action of hydroalcoholic extract, dichloromethane fraction and steroid α-spinasterol from Polygala sabulosa in LPS-induced peritonitis in mice. J Ethnopharmacol 151:144–150. https://doi.org/10.1016/j.jep.2013.10.009

    Article  CAS  Google Scholar 

  19. Bailey JA, Vincent GG, Burden RS (1976) The antifungal activity of glutinosone and capsidiol and their accumulation in virus-infected tobacco species. Physiol Plant Pathol 8:35–41. https://doi.org/10.1016/0048-4059(76)90005-9

    Article  CAS  Google Scholar 

  20. Yang EJ, Song KS (2021) The ameliorative effects of capsidiol isolated from elicited Capsicum annuum on mouse splenocyte immune responses and neuroinflammation. Phytother Res 35:1597–1608. https://doi.org/10.1002/ptr.6927

    Article  CAS  Google Scholar 

  21. Kim YJ et al (2021) Inhibitory effects of Gyeji-tang on MMP-9 activity and the expression of adhesion molecules in IL-4- and TNF-α-stimulated BEAS-2B cells. Plants (Basel) 10:951. https://doi.org/10.3390/plants10050951

    Article  CAS  Google Scholar 

  22. Kumari S et al (2016) Rapid screening and identification of phenolic antioxidants in Hydrocotyle sibthorpioides Lam. by UPLC–ESI-MS/MS. Food Chem 203:521–529. https://doi.org/10.1016/j.foodchem.2016.02.101

    Article  CAS  Google Scholar 

  23. Hoke GP, McWilliams GW (2008) Epidemiology of benign prostatic hyperplasia and comorbidities in racial and ethnic minority populations. Am J Med 121:S3–S10. https://doi.org/10.1016/j.amjmed.2008.05.021

    Article  Google Scholar 

  24. Wilson EM, French FS (1976) Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem 251:5620–5629. https://doi.org/10.1016/S0021-9258(17)33103-4

    Article  CAS  Google Scholar 

  25. Mcconnell JD (1991) The pathophysiology of benign prostatic hyperplasia. J Androl 12:356–363. https://doi.org/10.1002/j.1939-4640.1991.tb00272.x

    Article  CAS  Google Scholar 

  26. Roehrborn CG (2008) Pathology of benign prostatic hyperplasia. Int J Impot Res 20:S11–S18. https://doi.org/10.1038/ijir.2008.55

    Article  Google Scholar 

  27. Azzouni F et al (2012) The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol 2012:530121. https://doi.org/10.1155/2012/530121

    Article  Google Scholar 

  28. La Vignera S et al (2016) Endocrine control of benign prostatic hyperplasia. Andrology 4:404–411. https://doi.org/10.1111/andr.12186

    Article  CAS  Google Scholar 

  29. Kyprianou N, Tu H, Jacobs SC (1996) Apoptotic versus proliferative activities in human benign prostatic hyperplasia. Hum Pathol 27:668–675. https://doi.org/10.1016/S0046-8177(96)90396-2

    Article  CAS  Google Scholar 

  30. Schönenberger F et al (2015) Discrimination of cell cycle phases in PCNA-immunolabeled cells. BMC Bioinformatics 16:180. https://doi.org/10.1186/s12859-015-0618-9

    Article  CAS  Google Scholar 

  31. Barman J et al (2018) Apoptosis: mediator molecules, interplay with other cell death processes and therapeutic potentials. Curr Pharm Biotechnol 19:644–663. https://doi.org/10.2174/1389201019666180821093239

    Article  CAS  Google Scholar 

  32. Ribal MJ (2013) The link between benign prostatic hyperplasia and inflammation. Eur Urol Suppl 12:103–109. https://doi.org/10.1016/j.eursup.2013.08.001

    Article  Google Scholar 

  33. Wang L et al (2008) Chronic inflammation in benign prostatic hyperplasia: implications for therapy. Med Hypotheses 70:1021–1023. https://doi.org/10.1016/j.mehy.2007.08.022

    Article  Google Scholar 

  34. McLaren ID, Jerde TJ, Bushman W (2011) Role of interleukins, IGF and stem cells in BPH. Differentiation 82:237–243. https://doi.org/10.1016/j.diff.2011.06.001

    Article  CAS  Google Scholar 

  35. Yang X et al (2014) Abacopteris penangiana exerts testosterone-induced benign prostatic hyperplasia protective effect through regulating inflammatory responses, reducing oxidative stress and anti-proliferative. J Ethnopharmacol 157:105–113. https://doi.org/10.1016/j.jep.2014.09.025

    Article  CAS  Google Scholar 

  36. De Nunzio C, Presicce F, Tubaro A (2016) Inflammatory mediators in the development and progression of benign prostatic hyperplasia. Nat Rev Urol 13:613–626. https://doi.org/10.1038/nrurol.2016.168

    Article  CAS  Google Scholar 

  37. Chughtai B et al (2011) Role of inflammation in benign prostatic hyperplasia. Rev Urol 13:147–150

    Google Scholar 

  38. Baltaci S et al (2001) Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low-and high-grade prostatic intraepithelial neoplasia and prostatic carcinoma. BJU Int 88:100–103. https://doi.org/10.1046/j.1464-410x.2001.02231.x

    Article  CAS  Google Scholar 

  39. Wang W, Bergh A, Damber JE (2004) Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. Prostate 61:60–72. https://doi.org/10.1002/pros.20061

    Article  CAS  Google Scholar 

  40. Nakanishi Y et al (2001) Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines. Eur J Cancer 37:1570–1578. https://doi.org/10.1016/S0959-8049(01)00160-5

    Article  CAS  Google Scholar 

  41. Altavilla D et al (2012) Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia. Br J Pharmacol 167:95–108. https://doi.org/10.1111/j.1476-5381.2012.01969.x

    Article  CAS  Google Scholar 

  42. Inouye BM et al (2018) The emerging role of inflammasomes as central mediators in inflammatory bladder pathology. Curr Urol 11:57–72. https://doi.org/10.1159/000447196

    Article  CAS  Google Scholar 

  43. Jiang MY et al (2017) Mitochondrion-associated protein peroxiredoxin 3 promotes benign prostatic hyperplasia through autophagy suppression and pyroptosis activation. Oncotarget 8:80295–80302. https://doi.org/10.18632/oncotarget.17927

    Article  Google Scholar 

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Funding

This work was supported by research fund of Chungnam National University.

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Author notes

  1. Suyoung Park and Youn-Hwan Hwang have contributed equally to this work.

Authors and Affiliations

  1. Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon, 34134, South Korea

    Suyoung Park, Eun-Bok Baek, Eun-Ju Hong & Hyo-Jung Kwun

  2. Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672, Yuseong-daero, Yuseong-gu, Daejeon, 34054, South Korea

    Youn-Hwan Hwang

  3. Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30, Yeongudanji-ro, Cheongwon-gu, Cheongju, 28116, South Korea

    Young-Suk Won

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Contributions

Conceptualization: SP, Y-SW, and H-JK. Preparation and analysis of extracts: Y-HH. Data curation: SP, E-BB, and E-JH. Investigation: SP, Y-HH, Y-SW, and H-JK. Writing—original draft preparation: SP, Y-HH, and Y-SW. Writing—review and editing: SP, Y-SW, and H-JK. Supervision: Y-SW and H-JK. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Hyo-Jung Kwun.

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The authors declare that there are no conflicts of interest.

Ethical approval

All protocols for the studies were approved by the Animal Experimental Ethics Committee of Chungnam National University (Daejeon, South Korea; Approval No. CNU-00711).

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Park, S., Hwang, YH., Baek, EB. et al. Inhibitory effects of Hydrocotyle ramiflora on testosterone-induced benign prostatic hyperplasia in rats. Int Urol Nephrol 55, 17–28 (2023). https://doi.org/10.1007/s11255-022-03362-7

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