Abstract
Objective
To evaluate the effects of Xiaojin Pill (小金丸) in the treatment of Peyronie’s disease (PD) in a rat model.
Methods
Twenty-four male Sprague-Dawley rats were randomly divided into four groups with 6 in each: sham operation, PD model, vehicle control and Xiaojin Pill groups. The rats in the sham operation group received penile tunica albsginea (TA) injection with 50 μL vehicle, while the rats in the other 3 groups received 50 μL penile TA injection of 50 μg transforming growth factor (TGF)-β1. Forty-two days after the injection, rats in the vehicle control and Xiaojin Pill groups received 0.5 mL water and Xiaojin Pill solution (107 mg/kg of body weight), respectively by gavage for 28 days, while those in the sham operation and PD model groups did not receive any intervention. After intervention, the expressions of matrix metalloproteinase 2/9 (MMP2/9), nitric oxidesynthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured.
Results
Rats in the PD model and vehicle control groups presented obvious fibrosis in corpus cavernosum (CC) and demonstrated a significantly increased expressions of MMP2 and MMP9 in the CC compared with the sham operation group (all P<0.01). In contrast, the expressions of MMP2 and MMP9 in the Xiaojin Pill group were significantly down-regulated (both P<0.01). In addition, the levels of NOS and MDA in CC were significantly increased while the activity of SOD was decreased in the PD model and vehicle control groups compared with the sham operation group (all P<0.01). After Xiaojin Pill treatment, the levels of MDA, NOS and SOD appeared to be corrected (all P<0.01).
Conclusions
Xiaojin Pill could reduce fibrosis in the CC by decreasing the expressions of MMPs, NOS and MDA, and by increasing the activity of SOD. Therefore, Xiaojin Pill might be a therapeutic option for PD.
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References
Taylor FL, Levine LA. Peyronie’s disease. Urol Clin North Am 2007;34:517–534.
Serefoglu EC, Smith TM, Kaufman GJ, Liu GZ, Yafi FA, Hellstrom WJG. Factors associated with erectile dysfunction and the Peyronie’s disease questionnaire in patients with Peyronie disease. Urol Sci 2017;107:155–160.
Terlecki RP, Rasper AM. Data vs Dogma in Peyronie’s disease. Int Braz J Urol Sci 2016;42:1058–1061.
Sherer BA, Levine LA. Contemporary review of treatment options for Peyronie’s disease. Urol Sci 2016;95:16–24.
Nehra A, Alterowitz R, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh JJ, et al. Peyronie’s disease: AUA Guideline. J Urol Sci 2015;194:745–753.
Patel V, McGurk M. Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy. Br J Oral Maxillofac Surg Sci 2017;55:235–241.
Paulis G, Paulis A, Romano G, Barletta D, Fabiani A. Rationale of combination therapy with antioxidants in medical management of Peyronie’s disease: results of clinical application. Res Rep Urol Sci 2017;9:129–139.
Kevin AO, John RG, Thomas JW. A review of the epidemiology and treatment of Peyronie’s disease. Res Rep Urol 2016;8:61–70.
Gelfand RA, Vernet D, Kovanecz I, Rajfer J, Gonzalez-Cadavid NF. The transcriptional signatures of cells from the human Peyronie’s disease plaque and the ability of these cells to generate a plaque in a rat model suggest potential therapeutic targets. J Sex Med 2015;12:313–327.
Gonzalez-Cadavid NF, Rajfer J. Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie’s disease. Nat Clin Pract Urol 2005;2:291–297.
Haag SM, Hauck EW, Eickelberg O, Szardening-Kirchner C, Diemer T, Weidner W. Investigation of the antifibrotic effect of IFN-gamma on fibroblasts in a cell culture model of Peyronie’s disease. Eur Urol 2008;53:425–430.
Ali MM, Mahmoud AM, Master EL, Levitan I, Phillips SA. Role of matrix metalloproteinases and histone deacetylase in oxidative stress-induced degradation of the endothelial glycocalyx. Am J Physiol Heart Circ Physiol 2019;316:H647–H663.
Committee of Pharmacopoeia of the People’s Republic of China. Pharmacopoeia of the People’s Republic of China. Part I. Bejing: China Med Pharm Sci Tech Press;2015:568.
Feng Y, Qing J. Xiao Jin Pill joint with 6 flavour glutinous rehmannia treatment of Peyronie’s disease in 2 cases. Hunan J Tradit Chin Med (Chin) 2009;25:83.
Zhao YW, Li YP, Yi T. The effect of treatment of chronic hepatitis B liver fibrosis by Xiao Jin Pill. Chin Pharm (Chin) 2011;20:73.
Castiglione F, Hedlund P, Van der Aa F, Bivalacqua TJ, Rigatti P, Van Poppel H, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie’s disease. Eur Urol 2013;63:551–560.
Zorba OU, Sirma S, Ozgon G, Salabas E, Ozbek U, Van Poppel H, et al. Comparison of apoptotic gene expression profiles between Peyronie’s disease plaque and tunica albuginea. Adv Clin Exp Med 2012;21:607–614.
Lin CS, Lin G, Wang Z, Maddah SA, Lue TF. Upregulation of monocyte chemoattractant protein 1 and effects of transforming growth factor-beta 1 in Peyronie’s disease. Biochem Biophys Res Commun 2002;295:1014–1019.
Lopez JA, Jarow JP. Penile vascular evaluation of men with Peyronie’s disease. J Urol 1993;149:53–55.
Trost LW, Munarriz R, Wang R, Morey A, Levine L. External mechanical devices and vascular surgery for erectile dysfunction. J Sex Med 2016;13:1579–1617.
Rolle L, Falcone M, Ceruti C, Timpano M, Sedigh O, Ralph DJ, et al. A prospective multicentric international study on the surgical outcomes and patients’ satisfaction rates of the’ sliding ‘technique for end-stage Peyronie’s disease with severe shortening of the penis and erectile dysfunction. BJU Int 2016;117:814–820.
Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol 2008;214:199–210.
Jablonska Trypuc A, Matejczyk M, Rosochacki S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzyme Inhib Med Chem Sci 2016;31:177–183.
Davila HH, Ferrini MG, Rajfer J, Gonzalez-Cadavid NF. Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie’s disease. BJU Int 2003;91:830–838.
Giannandrea M, Parks WC. Diverse functions of matrix metalloproteinases during fibrosis. Dis Model Mech 2014;7:193–203.
Rosenbloom J, Mendoza FA, Jimenez SA. Strategies for antifibrotic therapies. Biochim Biophys Acta 2013;1832:1088–1103.
Wynn TA, Ramalingam TR. Mechanisms of fibrosis:therapeutic translation for fibrotic disease. Nat Med 2012;18:1028–1040.
Chen Y, Jiang QH, Luo ZH. Effect of Shexiang Baoxin Pill on immunological liver fibrosis in rats and its mechanism. Chin Tradit Herb Drugs (Chin) 2013;44:2563–2568.
Paulis G, Brancato T. Inflammatory mechanisms and oxidative stress in Peyronie’s disease: therapeutic "rationale" and related emerging treatment strategies. Inflamm Allergy Drug Targets Sci 2012;11:48–57.
Moro T, Nakao S, Sumiyoshi H, Ishii T, Miyazawa M, Ishii N, et al. A combination of mitochondrial oxidative stress and excess fat/calorie intake accelerates steatohepatitis by enhancing hepatic CC chemokine production in mice. PloS One 2016;11:e0146592.
Bivalacqua TJ, Champion HC, Leungwattanakij S, Yang DY, Hyun JS, Abdel-Mageed AB, et al. Evaluation of nitric oxide synthase and arginase in the induction of a Peyronie’s-like condition in the rat. J Androl 2001;22:497–506.
Matkov G, Levine LA, Storm DW. Peyronie’s disease affecting the younger male. Program and abstracts from the American Urological Association 95th Annual Meeting. April 29–May 4, 2000; Atlanta, Georgia, USA, 2000:abstr 743.
Xu HB, Li L, Liu GQ. Protection against hydrogen peroxideinduced cytotoxicity in PC12 cells by guggulsterone. Acta Pharm Sin (Chin) 2008;43:1190–1197.
Tan Y, Xu X, Zhou K, He J, Qu CQ, Gao XM. The study on hepatotoxicity of Mastic and Myrrha in rats. Chin Pharm Affairs (Chin) 2010;17:193–195.
Zhang YQ. Influence of Shexiang Baoxin Pills on oxidative stress in patients with unstable angina pectoris of coronary heart disease. Chin J Exp Med Formul (Chin) 2013;19:334–336.
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Guo J, Geng Q, and Wang F conceived and designed the study, analyzed the data and wrote the manuscript. OUYANG B, and Han Q designed, performed and analyzed the experiments shown in Figure 1. Chen SF, Li Z, Zhao Y, Gao QH, and Yu GJ designed, performed and analyzed the experiments shown in Figures 2 and 3.
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Supported by the China Postdoctoral Science Foundation (No. 178641)
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Geng, Q., Wang, F., Han, Q. et al. Antioxidant Mechanism of Xiaojin Pill (小金丸) for Treatment of Peyronie’s Disease in Rats Based on Matrix Metalloproteinases. Chin. J. Integr. Med. 25, 671–676 (2019). https://doi.org/10.1007/s11655-019-3203-7
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DOI: https://doi.org/10.1007/s11655-019-3203-7