DOI QR코드

DOI QR Code

Effects of Schisandra chinensis fruit extract and gomisin A on the contractility of penile corpus cavernosum smooth muscle: a potential mechanism through the nitric oxide - cyclic guanosine monophosphate pathway

  • Choi, Bo Ram (Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University) ;
  • Kim, Hye Kyung (College of Pharmacy, Kyungsung University) ;
  • Park, Jong Kwan (Department of Urology, Chonbuk National University and Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University)
  • Received : 2018.02.27
  • Accepted : 2018.04.10
  • Published : 2018.08.01

Abstract

BACKGROUND/OBJECTIVES: This study evaluated the effects and molecular mechanisms of the Schisandra chinensis fruit extract (SC) and its major compound gomisin A (GA), on the contractility of rabbit penile corpus cavernosum smooth muscle (PCCSM). MATERIALS/METHODS: PCCSM was exposed to SC or GA after appropriate pretreatment with nitric oxide synthase (NOS) blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker. Subsequently, we evaluated the cyclic nucleotide in the perfusate by radioimmunoassay, protein expression level of neuronal NOS (nNOS) and endothelial NOS (eNOS) by western blot, and the interaction of SC or GA with udenafil and rolipram. RESULTS: Both SC and GA induce PCCSM relaxations in a concentration-dependent manner. Pretreatment with NOS blocker, guanylate cyclase blocker, adenylyl cyclase blocker or protein kinase A blocker result in significantly decreased relaxation. SC and GA also induce the levels of cyclic nucleotide in the perfusate in a concentration-dependent manner. Perfusion with GA also showed significantly higher levels of eNOS protein. Furthermore, the udenafil and rolipram induced relaxations of PCCSM were enhanced after exposure to SC and GA. Our results indicate that SC and GA induce the relaxation of PCCSM via the nitric oxide (NO)-cGMP and cAMP signaling pathways. CONCLUSIONS: The SC and GA are potential alternative treatments for men who want to consume natural products to ameliorate erectile function, or who do not respond to the commercially available medicines.

Keywords

References

  1. Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol 2008;118:183-212. https://doi.org/10.1016/j.jep.2008.04.020
  2. He XG, Lian LZ, Lin LZ. Analysis of lignan constituents from Schisandra chinensis by liquid chromatography-electrospray mass spectrometry. J Chromatogr A 1997;757:81-7. https://doi.org/10.1016/S0021-9673(96)00685-1
  3. Kim EY, Baek IH, Rhyu MR. Cardioprotective effects of aqueous Schizandra chinensis fruit extract on ovariectomized and ballooninduced carotid artery injury rat models: effects on serum lipid profiles and blood pressure. J Ethnopharmacol 2011;134: 668-75. https://doi.org/10.1016/j.jep.2011.01.019
  4. Hikino H, Kiso Y, Taguchi H, Ikeya Y. Antihepatotoxic actions of lignoids from Schizandra chinensis fruits. Planta Med 1984;50:213-8. https://doi.org/10.1055/s-2007-969681
  5. Hu D, Cao Y, He R, Han N, Liu Z, Miao L, Yin J. Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates $A{\beta}$ 1-42-induced memory impairment in mice. Oxid Med Cell Longev 2012:721721.
  6. Kang S, Lee KP, Park SJ, Noh DY, Kim JM, Moon HR, Lee YG, Choi YW, Im DS. Identification of a novel anti-inflammatory compound, ${\alpha}$-cubebenoate from Schisandra chinensis. J Ethnopharmacol 2014;153:242-9. https://doi.org/10.1016/j.jep.2014.02.027
  7. Han DH, Lee JH, Kim H, Ko MK, Chae MR, Kim HK, So I, Jeon JH, Park JK, Lee SW. Effects of Schisandra chinensis extract on the contractility of corpus cavernosal smooth muscle (CSM) and Ca2+ homeostasis in CSM cells. BJU Int 2012;109:1404-13. https://doi.org/10.1111/j.1464-410X.2011.10567.x
  8. Liu W, Choi BR, Bak YO, Zhang LT, Zhou LX, Huang YR, Zhao C, Park JK. Cavernosum smooth muscle relaxation induced by Schisandrol A via the NO-cGMP signaling pathway. Cell Mol Biol 2016;62:115-9.
  9. Wespes E, Amar E, Hatzichristou D, Montorsi F, Pryor J, Vardi Y. Guidelines on erectile dysfunction. Eur Urol 2002;41:1-5. https://doi.org/10.1016/S0302-2838(01)00008-2
  10. Cho YJ, Hwang HS, Park HK, Jeong JG. Prevalence of erectile dysfunction and utilization of sexual counseling in community family medicine clinics. Korean J Fam Med 2009;30:617-25. https://doi.org/10.4082/kjfm.2009.30.8.617
  11. Lee JH, Choi JK, Kim SH, Cho KH, Kim YT, Choi SH, Jung UW. Association between periodontal flap surgery for periodontitis and vasculogenic erectile dysfunction in Koreans. J Periodontal Implant Sci 2017;47:96-105. https://doi.org/10.5051/jpis.2017.47.2.96
  12. Ghalayini IF. Nitric oxide-cyclic GMP pathway with some emphasis on cavernosal contractility. Int J Impot Res 2004;16:459-69. https://doi.org/10.1038/sj.ijir.3901256
  13. Paul V, Ekambaram P. Involvement of nitric oxide in learning & memory processes. Indian J Med Res 2011;133:471-8.
  14. Nunes KP, Webb RC. Mechanisms in erectile function and dysfunction: an overview. In: Nunes K, editor. Erectile Dysfunction: Disease-associated Mechanisms and Novel Insights into Therapy. London: InTech; 2012. Chapter 1.
  15. Toque HA, Caldwell RW. New approaches to the design and discovery of therapies to prevent erectile dysfunction. Expert Opin Drug Discov 2014;9:1447-69. https://doi.org/10.1517/17460441.2014.949234
  16. Recio P, Lopez PG, Hernandez M, Prieto D, Contreras J, Garcia- Sacristan A. Nitrergic relaxation of the horse corpus cavernosum. Role of cGMP. Eur J Pharmacol 1998;351:85-94. https://doi.org/10.1016/S0014-2999(98)00282-9
  17. Zhang G, Liu Y, Ruoho AE, Hurley JH. Structure of the adenylyl cyclase catalytic core. Nature 1997;386:247-53. https://doi.org/10.1038/386247a0
  18. Rhyu MR, Kim EY, Yoon BK, Lee YJ, Chen SN. Aqueous extract of Schizandra chinensis fruit causes endothelium-dependent and-independent relaxation of isolated rat thoracic aorta. Phytomedicine 2006;13:651-7. https://doi.org/10.1016/j.phymed.2006.02.003
  19. Zhao C, Chae HJ, Kim SH, Cui WS, Lee SW, Jeon JH, Park JK. A new perfusion model for studying erectile function. J Sex Med 2010;7:1419-28. https://doi.org/10.1111/j.1743-6109.2009.01652.x
  20. Cui X, Lee SJ, Kim SZ, Kim SH, Cho KW. Effects of pituitary adenylate cyclase activating polypeptide27 on cyclic AMP efflux and atrial dynamics in perfused beating atria. Eur J Pharmacol 2000;402: 129-37. https://doi.org/10.1016/S0014-2999(00)00514-8
  21. Kim HK, Bak YO, Choi BR, Zhao C, Lee HJ, Kim CY, Lee SW, Jeon JH, Park JK. The role of the lignan constituents in the effect of Schisandra chinensis fruit extract on penile erection. Phytother Res 2011;25:1776-82. https://doi.org/10.1002/ptr.3486
  22. Seok YM, Choi YW, Kim GD, Kim HY, Takuwa Y, Kim IK. Effects of gomisin A on vascular contraction in rat aortic rings. Naunyn Schmiedebergs Arch Pharmacol 2011;383:45-56. https://doi.org/10.1007/s00210-010-0571-0
  23. Park JY, Lee SJ, Yun MR, Seo KW, Bae SS, Park JW, Lee YJ, Shin WJ, Choi YW, Kim CD. Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta. Planta Med 2007;73:1537-42. https://doi.org/10.1055/s-2007-993757
  24. McMahon CG. Erectile dysfunction. Intern Med J 2014;44:18-26. https://doi.org/10.1111/imj.12325
  25. Kandeel FR, Koussa VK, Swerdloff RS. Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr Rev 2001;22:342-88. https://doi.org/10.1210/edrv.22.3.0430
  26. Gonzalez-Cadavid NF, Rajfer J. The pleiotropic effects of inducible nitric oxide synthase (iNOS) on the physiology and pathology of penile erection. Curr Pharm Des 2005;11:4041-6. https://doi.org/10.2174/138161205774913372
  27. Haas CA, Seftel AD, Razmjouei K, Ganz MB, Hampel N, Ferguson K. Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase. Urology 1998;51:516-22. https://doi.org/10.1016/S0090-4295(97)00715-2
  28. Park JY, Shin HK, Lee YJ, Choi YW, Bae SS, Kim CD. The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta. J Ethnopharmacol 2009;121:69-73. https://doi.org/10.1016/j.jep.2008.09.031
  29. Wespes E, Amar E, Hatzichristou D, Hatzimouratidis K, Montorsi F, Pryor J, Vardi Y. EAU guidelines on erectile dysfunction: an update. Eur Urol 2006;49:806-15. https://doi.org/10.1016/j.eururo.2006.01.028
  30. Huang SA, Lie JD. Phosphodiesterase-5 (PDE5) inhibitors in the management of erectile dysfunction. P T 2013;38:407-19.
  31. DeBusk RF, Pepine CJ, Glasser DB, Shpilsky A, DeRiesthal H, Sweeney M. Efficacy and safety of sildenafil citrate in men with erectile dysfunction and stable coronary artery disease. Am J Cardiol 2004;93:147-53. https://doi.org/10.1016/j.amjcard.2003.09.030
  32. Wachtel H. Potential antidepressant activity of rolipram and other selective cyclic adenosine 3',5'-monophosphate phosphodiesterase inhibitors. Neuropharmacology 1983;22:267-72. https://doi.org/10.1016/0028-3908(83)90239-3
  33. Beavo JA. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 1995;75:725-48 https://doi.org/10.1152/physrev.1995.75.4.725

Cited by

  1. The Effect of Schisandra chinensis Baillon on Cross-Talk between Oxidative Stress, Endoplasmic Reticulum Stress, and Mitochondrial Signaling Pathway in Testes of Varicocele-Induced SD Rat vol.20, pp.22, 2018, https://doi.org/10.3390/ijms20225785
  2. Robust Optimization Approaches for a Natural Pharmaceutical Complex Product of Atractylodes Japonica Koidz and Schisandra Chinensis vol.10, pp.19, 2018, https://doi.org/10.3390/app10197006
  3. A Study on the Fabrication of an Effective Natural Substance Based on Schisandra chinensis Extracted Fermentation vol.14, pp.None, 2018, https://doi.org/10.2147/ccid.s336280