Article Data

  • Views 338
  • Dowloads 154

Original Research

Open Access

Euodia rutaecarpa fruit attenuates testosterone-induced benign prostatic hyperplasia in rats by inhibiting 5α-reductase activity and androgen receptor signaling pathway

  • Yung Hyun Choi1,2,*,

1Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases and Anti-Aging Research Center, Dong-Eui University, 47227 Busan, Republic of Korea

2Department of Biochemistry, College of Korean Medicine, Dong-Eui University, 47227 Busan, Republic of Korea

DOI: 10.22514/jomh.2024.183 Vol.20,Issue 11,November 2024 pp.28-37

Submitted: 05 June 2024 Accepted: 30 July 2024

Published: 30 November 2024

*Corresponding Author(s): Yung Hyun Choi E-mail: choiyh@deu.ac.kr

Abstract

In this study, effect of an ethanol extract of Euodia rutaecarpa fruit (EER), known to have various pharmacological effects, on benign prostatic hyperplasia (BPH) was evaluated. To induce BPH in an in vivo animal model, testosterone propionate (TP) was injected to rats. EER was administered orally with TP injection. Finasteride, a 5α-reductase inhibitor, was used as a positive control. After all mice were sacrificed at the end of the experiment, pathological changes in prostate tissues and levels of key biomarkers involved in BPH development were assessed. Oral administration of EER significantly suppressed TP-induced BPH by diminishing prostate weight, lumen size and epithelial thickness. EER also abrogated the expression of prostate-specific antigen, proliferating cell nuclear antigen, and 5α-reductase type 2 induced by TP. In addition, serum levels of testosterone, dihydrotestosterone (DHT) and prostate specific antigen were elevated in TP challenged rats but decreased in EER-administered rats. Moreover, the improvement effect of EER on TP-induced BPH was associated with decreased expression of androgen receptor (AR) and its coactivators. The current findings show that EER can protect against BPH by attenuating the activation of 5α-reductase and inhibiting the AR signaling pathway, suggesting that EER has great potential in blocking BPH pathogenesis.


Keywords

Euodia rutaecarpa fruit; Benign prostatic hyperplasia; Androgen receptor; Dihydrotestosterone; 5α-reductase


Cite and Share

Yung Hyun Choi. Euodia rutaecarpa fruit attenuates testosterone-induced benign prostatic hyperplasia in rats by inhibiting 5α-reductase activity and androgen receptor signaling pathway. Journal of Men's Health. 2024. 20(11);28-37.

References

[1] Chen L, Hu Y, Ye Z, Li L, Qian H, Wu M, et al. Major indole alkaloids in Evodia rutaecarpa: the latest insights and review of their impact on gastrointestinal diseases. Biomedicine & Pharmacotherapy. 2023; 167: 115495.

[2] Li M, Wang C. Traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the fruit of Tetradium ruticarpum: a review. Journal of Ethnopharmacology. 2020; 263: 113231.

[3] Cao Q, Dong P, Han H. Therapeutic effects of the major alkaloid constituents of Evodia rutaecarpa in Alzheimer’s disease. Psychogeriatrics. 2024; 24: 443–457.

[4] Li D, Huang Z, Xu X, Li Y. Promising derivatives of rutaecarpine with diverse pharmacological activities. Frontiers in Chemistry. 2023; 11: 1199799.

[5] Li X, Ge J, Zheng Q, Zhang J, Sun R, Liu R. Evodiamine and rutaecarpine from Tetradium ruticarpum in the treatment of liver diseases. Phytomedicine. 2020; 68: 153180.

[6] Fang Z, Tang Y, Ying J, Tang C, Wang Q. Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa. Chinese Medicine. 2020; 15: 82.

[7] Zhao Z, He X, Han W, Chen X, Liu P, Zhao X, et al. Genus Tetradium L.: a comprehensive review on traditional uses, phytochemistry, and pharmacological activities. Journal of Ethnopharmacology. 2019; 231: 337–354.

[8] Qin J, Liao CN, Chen WW, Li HY, Su J, Wu XD, et al. New limonoids and quinolone alkaloids with cytotoxic and anti-platelet aggregation activities from Evodia rutaecarpa (Juss.) Benth. Fitoterapia. 2021; 152: 104875.

[9] Han SY, Im DS. Evodiamine alleviates 2,4-dinitro-1-chloro-benzene-induced atopic dermatitis-like symptoms in BALB/c mice. Life. 2024; 14: 494.

[10] Jiang H, Qiu J, Deng X, Li D, Tao T. Potential active compounds and common mechanisms of Evodia rutaecarpa for Alzheimer’s disease comorbid pain by network pharmacology analysis. Heliyon. 2023; 9: e18455.

[11] Xian S, Lin Z, Zhou C, Wu X. The protective effect of evodiamine in osteoarthritis: an in vitro and in vivo study in mice model. Frontiers in Pharmacology. 2022; 13: 899108.

[12] Yeh TH, Lin JY. Acorus gramineusand and Euodia ruticarpa steam distilled essential oils exert anti-inflammatory effects through decreasing Th1/Th2 and pro-/anti-inflammatory cytokine secretion ratios in vitro. Biomolecules. 2020; 10: 338.

[13] Tian KM, Li JJ, Xu SW. Rutaecarpine: a promising cardiovascular protective alkaloid from Evodia rutaecarpa (Wu Zhu Yu). Pharmacological Research. 2019; 141: 541–550.

[14] Hu RD, Zhu WL, Lin WY, Qiu YH, Wu GL, Ding XY, et al. Ethanol extract of Evodia lepta Merr. ameliorates cognitive impairment through inhibiting NLRP3 inflammasome in scopolamine-treated mice. Aging. 2024; 16: 2385–2397.

[15] Zhang Y, Wang J, Wang C, Li Z, Liu X, Zhang J, et al. Pharmacological basis for the use of evodiamine in Alzheimer’s disease: antioxidation and antiapoptosis. International Journal of Molecular Sciences. 2018; 19: 1527.

[16] Yuan SM, Gao K, Wang DM, Quan XZ, Liu JN, Ma CM, et al. Evodiamine improves congnitive abilities in SAMP8 and APP (swe)/PS1(ΔE9) transgenic mouse models of Alzheimer’s disease. Acta Pharmacologica Sinica. 2011; 32: 295–302.

[17] Corti M, Lorenzetti S, Ubaldi A, Zilli R, Marcoccia D. Endocrine disruptors and prostate cancer. International Journal of Molecular Sciences. 2022; 23: 1216.

[18] Chughtai B, Forde JC, Thomas DD, Laor L, Hossack T, Woo HH, et al. Benign prostatic hyperplasia. Nature Reviews Disease Primers. 2016; 2: 16031.

[19] Torabinejad S, Miro C, Barone B, Imbimbo C, Crocetto F, Dentice M. The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications. European Thyroid Journal. 2023; 12: e220228.

[20] Madersbacher S, Sampson N, Culig Z. Pathophysiology of benign prostatic hyperplasia and benign prostatic enlargement: a mini-review. Gerontology. 2019; 65: 458–464.

[21] Loughlin KR. The prostate as an endocrine organ: Its modulation of serum testosterone. Urologic Clinics of North America. 2022; 49: 695–697.

[22] Vickman RE, Franco OE, Moline DC, Vander Griend DJ, Thumbikat P, Hayward SW. The role of the androgen receptor in prostate development and benign prostatic hyperplasia: a review. Asian Journal of Urology. 2020; 7: 191–202.

[23] Chislett B, Chen D, Perera ML, Chung E, Bolton D, Qu LG. 5-α reductase inhibitors use in prostatic disease and beyond. Translational Andrology and Urology. 2023; 12: 487–496.

[24] He W, Ding T, Niu Z, Hao C, Li C, Xu Z, et al. Reoperation after surgical treatment for benign prostatic hyperplasia: a systematic review. Frontiers in Endocrinology. 2023; 14: 1287212.

[25] Gwon YN, Park JJ, Yang WJ, Doo SW, Kim JH, Kim DK. Comparing effects of α-blocker management on acute urinary retention secondary to benign prostatic hyperplasia: a systematic review and network meta-analysis. Prostate International. 2023; 11: 91–99.

[26] Müderrisoglu AE, de la Rosette JJMCH, Michel MC. Potential side effects of currently available pharmacotherapies in male lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Expert Opinion on Drug Safety. 2023; 22: 1213–1224.

[27] Bapir R, Bhatti KH, Eliwa A, García-Perdomo HA, Gherabi N, Hennessey D, et al. Effect of α-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis. Archivio Italiano di Urologia e Andrologia. 2022; 94: 252–263.

[28] Romero Pérez P. Post-finasteride syndrome. Literature review. Archivos Españoles de Urología. 2022; 75: 382–399.

[29] Park E, Lee MY, Seo CS, Jang JH, Kim YU, Shin HK. Ethanol extract of Evodia rutaecarpa attenuates cell growth through caspase-dependent apoptosis in benign prostatic hyperplasia-1 cells. Nutrients. 2018; 10: 523.

[30] Kiba A, Saha D, Das BK. Exploration of the anti-diabetic potential of hydro-ethanolic leaf extract of Koenigia polystachya L.: an edible wild plant from Northeastern India. Laboratory Animal Research. 2023; 39: 21.

[31] Hwangbo H, Kim MY, Ji SY, Park BS, Kim T, Yoon S, et al. Mixture of Corni Fructus and Schisandrae Fructus improves testosterone-induced benign prostatic hyperplasia through regulating 5α-reductase 2 and androgen receptor. Nutrition Research and Practice. 2023; 17: 32–47.

[32] Gao P, Duan W, Shi H, Wang Q. Silencing circPalm2 inhibits sepsis-induced acute lung injury by sponging miR-376b-3p and targeting MAP3K1. Toxicological Research. 2023; 39: 275–294.

[33] Kim A, Kim AR, Jeon YE, Yoo YJ, Yang YM, Bak EJ. TRPC expression in human periodontal ligament cells and the periodontal tissue of periodontitis mice: a preliminary study. Laboratory Animal Research. 2023; 39: 19.

[34] Zhang RS, Liu YY, Zhu PF, Jin Q, Dai Z, Luo XD. Furostanol saponins from Asparagus cochinchinensis and their cytotoxicity. Natural Products and Bioprospecting. 2021; 11: 651–658.

[35] Varaprasad GL, Gupta VK, Prasad K, Kim E, Tej MB, Mohanty P, et al. Recent advances and future perspectives in the therapeutics of prostate cancer. Experimental Hematology & Oncology. 2023; 12: 80.

[36] Cózar JM, Hernández C, Miñana B, Morote J, Alvarez-Cubero MJ. The role of prostate-specific antigen in light of new scientific evidence: an update in 2020. Actas Urológicas Españolas. 2021; 45: 21–29.

[37] Li X, Xiong H, Mou X, Huang C, Thomas ER, Yu W, et al. Androgen receptor cofactors: a potential role in understanding prostate cancer. Biomedicine & Pharmacotherapy. 2024; 173: 116338.

[38] Sharifi N, Figg WD. Androgen receptor modulation: lessons learned from beyond the prostate. Cancer Biology & Therapy. 2007; 6: 1358–1359.

[39] Hu YC, Yeh S, Yeh SD, Sampson ER, Huang J, Li P, et al. Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer. Journal of Biological Chemistry. 2020; 295: 17382.

[40] Daniels G, Jha R, Shen Y, Logan SK, Lee P. Androgen receptor coactivators that inhibit prostate cancer growth. American Journal of Clinical and Experimental Urology. 2014; 2: 62–70.

[41] Culig Z, Puhr M. Androgen receptor-interacting proteins in prostate cancer development and therapy resistance. The American Journal of Pathology. 2024; 194: 324–334.

[42] Rohira AD, Lonard DM, O’Malley BW. Emerging roles of steroid receptor coactivators in stromal cell responses. Journal of Endocrinology. 2021; 248: R41–R50.

[43] Senapati D, Sharma V, Rath SK, Rai U, Panigrahi N. Functional implications and therapeutic targeting of androgen response elements in prostate cancer. Biochimie. 2023; 214: 188–198.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus: CiteScore 0.9 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (https://kanalregister.hkdir.no/publiseringskanaler/Forside).

Submission Turnaround Time

Conferences

Top