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BMC Complementary Medicine and Therapies

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Open Access 01-12-2017 | Research article

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

Authors: Woo-Young Jeon, Ohn Soon Kim, Chang-Seob Seo, Seong Eun Jin, Jung-Ae Kim, Hyeun-Kyoo Shin, Yong-ung Kim, Mee-Young Lee

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

Benign prostatic hyperplasia (BPH) is non-cancerous condition of enlargement of the prostate, a common occurrence in older men. The immature fruits of Poncirus trifoliata (L.) Rafinesque (Rutaceae), Ponciri Fructus are widely used in traditional oriental medicine for the therapy of various diseases. However, little is known about the mechanism underlying the pathogenesis of BPH. In the present study, we investigated the protective effects of a Ponciri Fructus extract (PFE) on the development of BPH in a in a rat model of BPH induced by testosterone propionate (TP).

Methods

Male Sprague Dawley rats were used as a model of BPH after its induction by daily subcutaneous injections of TP/corn oil, for a period of four weeks. PFE was administrated daily 1 h before TP/corn oil injection by oral gavage at a dose level of 200 mg/kg during the 4 weeks of TP/corn oil injections. All rats were sacrificed at the end of the experiment, we measured the relative prostate weight, the levels of testosterone and dihydrotestosterone (DHT), histological changes, activities of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase), and expression of proliferating cell nuclear antigen (PCNA). In addition, we also measured the inhibition (%) of 5α-reductase in the prostatic tissue.

Results

Our findings indicate that PFE significantly inhibited the development of BPH; decreased the relative prostate weight, the level of testosterone and DHT in serum and prostatic tissue, prostatic hyperplasia, expression of PCNA, and increased the antioxidant enzymes. Moreover, PFE showed a weak inhibitory activity on 5α-reductase.

Conclusions

These results suggest that PFE may be used as a therapeutic agent for BPH via antiproliferative and antioxidant effects.

Untergasser G, Madersbacher S, Berger P. Benign prostatic hyperplasia: age-related tissue-remodeling. Exp Gerontol. 2005;40:121–8. doi:10.1016/j.exger.2004.12.008.CrossRefPubMed

Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am. 2011;95:87–100. doi:10.1016/j.mcna.2010.08.013.CrossRefPubMed

Lucia MS, Lambert JR. Growth factors in benign prostatic hyperplasia: basic science implications. Curr Urol Rep. 2008;9:272–8.CrossRefPubMed

Andriole G, Bruchovsky N, Chung LW, Matsumoto AM, Rittmaster R, Roehrborn C, Russell D, Tindall D. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol. 2004;172:1399–403.CrossRefPubMed

Carson C 3rd, Rittmaster R. The role of dihydrotestosterone in benign prostatic hyperplasia. Urology. 2003;61:2–7.CrossRefPubMed

Bostanci Y, Kazzazi A, Momtahen S, Laze J, Djavan B. Correlation between benign prostatic hyperplasia and inflammation. Curr Opin Urol. 2013;23:5–10. doi:10.1097/MOU.0b013e32835abd4a.CrossRefPubMed

Sarbishegi M, Khani M, Salimi S, Valizadeh M, Sargolzaei Aval F. Antiproliferative and antioxidant effects of Withania Coagulans extract on benign prostatic hyperplasia in rats. Nephrourol Mon. 2016;8:e33180. doi:10.5812/numonthly.33180.PubMedPubMedCentral

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;157:105–13. doi:10.1016/j.jep.2014.09.025.CrossRefPubMed

KAPE: Handbook of the Korea Pharmacopoeia. 9th ed. Shinilbooks. Korea: Seoul; 2008. p. 1176–7.

10.

Shin EM, Zhou HY, Xu GH, Lee SH, Merfort I, Kim YS. Anti-inflammatory activity of hispidol a 25-methyl ether, a triterpenoid isolated from Ponciri Immaturus Fructus. Eur J Pharmacol. 2010;627:318–24. doi:10.1016/j.ejphar.2009.10.036.CrossRefPubMed

11.

Lee JH, Lee SH, Kim YS, Jeong CS. Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata on potential gastric disease. Phytother Res. 2009;23:1748–53. doi:10.1002/ptr.2840.CrossRefPubMed

12.

Seo CS, Jeong SJ, Yoo SR, Lee NR, Shin HK: Quantitative Analysis and In vitro Anti-inflammatory Effects of Gallic Acid, Ellagic Acid, and Quercetin from Radix Sanguisorbae. Pharmacogn Mag 2016, 12:104–108. doi:10.4103/0973-1296.177908

13.

Shin IS, Lee MY, Jung DY, Seo CS, Ha HK, Shin HK. Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia. Food Chem Toxicol. 2012;50:884–8. doi:10.1016/j.fct.2012.01.007.CrossRefPubMed

14.

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;626:262–5. doi:10.1016/j.ejphar.2009.09.037.CrossRefPubMed

15.

Jeon WY, Shin IS, Shin HK, Lee MY. Gastroprotective effect of the traditional herbal medicine, Sipjeondaebo-tang water extract, against ethanol-induced gastric mucosal injury. BMC Complement Altern Med. 2014;14:373. doi:10.1186/1472-6882-14-373.CrossRefPubMedPubMedCentral

16.

Lim HS, Yeji K, Seo CS, Yoo SR, Jin SE, Shin HK, Jeong SJ: Chungsimyeonja-eum inhibits inflammatory responses in RAW 264.7 macrophages and HaCaT keratinocytes. BMC Complement Altern Med 2015, 15:371. doi: 10.1186/s12906-015-0902-2.

17.

Kim S, Kim Y, Ma E. Synthesis and 5α-reductase inhibitory activity of C21 steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes. Molecules. 2011;17:355–68. doi:10.3390/molecules17010355.CrossRefPubMed

18.

Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25–61. doi:10.1146/annurev.bi.63.070194.000325.CrossRefPubMed

19.

Dunnett CW. New tables for multiple comparisons with control. Biometrics. 1964;20:482–91.CrossRef

20.

Afriyie DK, Asare GA, Bugyei K, Adjei S, Lin JM, Peng J, Hong ZF. Treatment of benign prostatic hyperplasia with Croton Membranaceus in an experimental animal model. J Ethnopharmacol. 2014;157:90–8. doi:10.1016/j.jep.2014.09.007.CrossRefPubMed

21.

Pais P. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5alpha-reductase II. Adv Ther. 2010;27:555–63. doi:10.1007/s12325-010-0041-6.CrossRefPubMed

22.

Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation. 2011;82:184–99. doi:10.1016/j.diff.2011.04.006.CrossRefPubMedPubMedCentral

23.

Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F, Vale W, Castellucci M. Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update. 2011;17:772–90. doi:10.1093/humupd/dmr031.CrossRefPubMedPubMedCentral

24.

Shen HN, Xu Y, Jiang ZZ, Huang X, Zhang LY, Wang T. Inhibitory effects of Tripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats. Chin J Nat Med. 2015;13:421–7. doi:10.1016/S1875-5364(15)30035-2.PubMed

25.

Ammar AE, Esmat A, Hassona MD, Tadros MG, Abdel-Naim AB, Guns ES. The effect of pomegranate fruit extract on testosterone-induced BPH in rats. Prostate. 2015;75:679–92. doi:10.1002/pros.22951.CrossRefPubMed

26.

Sies H. Strategies of antioxidant defense. Eur J Biochem. 1993;215:213–9.CrossRefPubMed

27.

Kumar VS, Rajmane AR, Adil M, Kandhare AD, Ghosh P, Bodhankar SL. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats. J Biomed Res. 2014;28:132–45. doi:10.7555/JBR.27.20120082.PubMed

28.

Cassani J, Araujo AG, Martínez-Vázquez M, Manjarrez N, Moreno J, Estrada-Reyes R. Anxiolytic-like and antinociceptive effects of 2(S)-neoponcirin in mice. Molecules. 2013;18:7584–99. doi:10.3390/molecules18077584.CrossRefPubMed

29.

Saralamma VV, Nagappan A, Hong GE, Lee HJ, Yumnam S, Raha S, Heo JD, Lee SJ, Lee WS, Kim EH, Kim GS. Poncirin induces apoptosis in AGS human gastric cancer cells through extrinsic apoptotic pathway by up-regulation of Fas ligand. Int J Mol Sci. 2015;16:22676–91. doi:10.3390/ijms160922676.CrossRefPubMed

30.

Sim MO, Lee HI, Ham JR, Seo KI, Kim MJ, Lee MK. Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats. Nutr Res Pract. 2015;9:364–9. doi:10.4162/nrp.2015.9.4.364.CrossRefPubMedPubMedCentral

31.

Guo W, Sun J, Jiang L, Duan L, Huo M, Chen N, Zhong W, Wassy L, Yang Z, Feng H. Imperatorin attenuates LPS-induced inflammation by suppressing NF-κB and MAPKs activation in RAW 264.7 macrophages. Inflammation. 2012;35:1764–72. doi:10.1007/s10753-012-9495-9.CrossRefPubMed

32.

Okuyama S, Morita M, Kaji M, Amakura Y, Yoshimura M, Shimamoto K, Ookido Y, Nakajima M, Furukawa Y. Auraptene acts as an anti-inflammatory agent in the mouse brain. Molecules. 2015;20:20230–9. doi:10.3390/molecules201119691.CrossRefPubMed

Title: Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats
Authors: Woo-Young Jeon
Ohn Soon Kim
Chang-Seob Seo
Seong Eun Jin
Jung-Ae Kim
Hyeun-Kyoo Shin
Yong-ung Kim
Mee-Young Lee
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-017-1877-y

At a glance: The STEP trials

Springer Medicine

Inhibitory effects of Ponciri Fructus on testosterone-induced benign prostatic hyperplasia in rats

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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