The efficacy and molecular mechanism of the effect of schisandrin b on the treatment of erectile dysfunction

Document Type : Original Article

Authors

Department of Urology and Andrology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200001, People’s Republic of China

Abstract

Objective(s): The purpose of this study is to determine the efficacy and molecular mechanism of the effect of schisandrin b (SCHB) on treating erectile dysfunction (ED) in a rat model with bilateral cavernous crushing nerve injury.
Materials and Methods: The ED rat model was established with bilateral cavernous nerve crushing, and then confirmed by apomorphine. Fifty healthy eight-week-old ED rats were randomly assigned into five group, including control group (sham surgery), bilateral cavernous nerve crushing injury group (BCNC), BCNC with low SCHB (100 mg/d), BCNC with medium SCHB (200 mg/d) and BCNC with high SCHB (400 mg/d). For the last three groups, SCHB was given for 2 months. Then, we examined intracavernosal pressure (ICP), cyclic nucleotides (cAMP, cGMP), endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS) in all groups.
Results: In the study of ICP, SCHB was able to improve ED in a dose-dependent manner. In addition, as compared to the BCNC group, the relative expression of eNOS and nNOS in medium and high concentration of SCHB-treated groups are higher than BCNC group. Moreover, all groups treated with SCHB showed a significant higher expression level of cAMP and cGMP.
Conclusion: These results suggested that SCHB were able to significantly improve the ED on rat model through the NO-cGMP and cAMP- protein kinase A (PKA) pathway.

Keywords

Main Subjects


1. Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2:759-770.
2. Labazi H. Nitroxyl anion as a novel relaxant molecule in the rat pudendal artery and metformin as treatment for angiotensin II-induced erectile dysfunction (Doctoral dissertation). 2012.
3. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am 2005;32:379-395.
4. Dhir RR, Lin H-C, Canfield SE, Wang R. Combination therapy for erectile dysfunction: an update review. Asian J Androl 2011;13:382.
5. Sommer F, Engelmann U. Future options for combination therapy in the management of erectile dysfunction in older men. Drugs Aging 2004;21:555-564.
6. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. “CA Cancer J Clin 2010;60:277-300.
7. Walsh PC, Marschke P, Ricker D, Burnett AL. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology. 2000;55:58-61.
8. Wang R. Penile rehabilitation after radical prostatectomy: Where do we stand and where are we going? J Sex Med 2007;4:1085-1097.
9. Litwin MS, Hays RD, Fink A, Ganz PA, Leake B, Leach GE, et al. Quality-of-life outcomes in men treated for localized prostate cancer. JAMA. 1995;273:129-135.
10. Levine LA, Greenfield JM, Estrada CR. Erectile dysfunction following surgical correction of Peyronie’s disease and a pilot study of the use of sildenafil citrate rehabilitation for postoperative erectile dysfunction. J Sex Med 2005;2:241-247.
11. Stanford JL, Feng Z, Hamilton AS, Gilliland FD, Stephenson RA, Eley JW, et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA. 2000;283:354-360.
12. Montorsi F, Briganti A, Salonia A, Rigatti P, Burnett AL. Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol 2004;45:123-133.
13. Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D’Amico AV, Dmochowski RR, et al. Erectile function outcome reporting after clinically localized prostate cancer treatment. J Urol 2007;178:597-601.
14. Kim HK, Bak YO, Choi BR, Zhao C, Lee HJ, Kim CY, et al. The role of the lignan constituents in the effect of Schisandra chinensis fruit extract on penile erection. Phytother Res 2011;25:1776-1782.
15. Chiu PY, Mak DHF, Poon MKT, Ko KM. In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta medica. 2002;68:951-956.
16. Wu MD, Huang RL, Kuo LM, Hung CC, Ong CW, Kuo YH. The anti‐HBsAg and anti‐HBeAg C18 dibenzocyclooctadiene lignans from Kadsura matsudai and Schizandra arisaensis. Chem Pharm Bull (Tokyo). 2003;107:298-301.
17. Choi Y-W, Takamatsu S, Khan SI, Srinivas PV, Ferreira D, Zhao J, et al. Schisandrene, a dibenzocyclooctadiene lignan from schisandra c hinensis: structure− antioxidant activity relationships of dibenzocyclooctadiene lignans. J Nat Prod 2006;69:356-359.
18. Zhao C, Kim SH, Lee SW, Jeon JH, Kang KK, Choi SB, et al. Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. BJU Int 2011;107:1943-1947.
19. Feldman HA, Johannes CB, Derby CA, Kleinman KP, Mohr BA, Araujo AB, et al. Erectile dysfunction and coronary risk factors: prospective results from the Massachusetts male aging study. Prev Med 2000;30:328-338.
20. Seyam RM, Huynh HT, Brock GB. Neuronal and endothelial nitric oxide synthase isoforms: quantification of protein and mRNA in the normal rat penis. Int J Impot Res 1999;11:301-308.
21. Thorve VS, Kshirsagar AD, Vyawahare NS, Joshi VS, Ingale KG, Mohite RJ. Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management. J Diabetes Complications 2011;25:129-136.
22. Cho MC, Park K, Chai JS, Lee SH, Kim SW, Paick JS. Involvement of sphingosine‐1‐phosphate/RhoA/Rho‐kinase signaling pathway in corporal fibrosis following cavernous nerve injury in male rats. J Sex Med 2011;8:712-721.