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Effects of ginsenoside on large-conductance KCa channels in human corporal smooth muscle cells

International Journal of Impotence Research volume 23, pages 193–199 (2011)Cite this article

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Abstract

Ginseng was known to be an effective natural product that enhances penile erection. However, the precise biological function and mechanisms of action of ginseng with regard to erectile function remain unknown. The principal objective of this study was to identify ginsenoside (principal molecular ingredients of ginseng)-induced activation of large-conductance KCa channel in human corporal smooth muscle cells, and to determine ginseng's mechanism of action on penile erection. Electrophysiological studies using cultured human corporal smooth muscle cells were conducted. We evaluated the effects of total ginsenosides (TGS) and ginsenoside Rg3 on large-conductance KCa channel by determining whole-cell currents and single-channel activities. There was an increase in outward current dependent on TGS concentration (at +60 mV, 1 μg ml−1; 168.3±59.3%, n=6, P<0.05, 10 μg ml−1; 173.2±36.8%, n=4, P<0.05, 50 μg ml−1; 295.3±62.3%, n=19, P<0.001, 100 μg ml−1; and 462.3±97.1%, n=5, P<0.001) and Rg3 concentration (at +60 mV, 1 μM (0.78 μg ml−1); 222.8±64.8%, n=11, P<0.0001, 10 μM; 672.6±137.1%, n=10, P<0.0001, 50 μM; and 1713.3±234.7%, n=15, P<0.001) in the solution that was blocked completely by tetraethylammonium (TEA). Channel opening in cell-attached mode and channel activity in the inside-out membrane patches was also increased significantly by 50 μg of TGS or 10 μM of Rg3. The results of this study suggested that the activation of large-conductance KCa channels by ginsenoside could be one mechanism of ginsenoside-induced relaxation in corporal smooth muscle.

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References

  1. Adimoelja A . Phytochemicals and the breakthrough of traditional herbs in the management of sexual dysfunctions. Int J Androl 2000; 23 (Suppl 2): 82–84.

    Article  CAS  Google Scholar 

  2. Bahrke MS, Morgan WR . Evaluation of the ergogenic properties of ginseng: an update. Sports Med 2000; 29: 113–133.

    Article  CAS  Google Scholar 

  3. Crimmel AS, Conner CS, Monga M . Withered Yang: a review of traditional Chinese medical treatment of male infertility and erectile dysfunction. J Androl 2001; 22: 173–182.

    CAS  PubMed  Google Scholar 

  4. Lentz A, Gravitt K, Carson CC, Marson L . Acute and chronic dosing of Lepidium meyenii (Maca) on male rat sexual behavior. J Sex Med 2007; 4: 332–339; discussion 9-40.

    Article  Google Scholar 

  5. Afolayan AJ, Yakubu MT . Erectile dysfunction management options in Nigeria. J Sex Med 2009; 6: 1090–1102.

    Article  Google Scholar 

  6. Lee TK, Johnke RM, Allison RR, O’Brien KF, Dobbs Jr LJ . Radioprotective potential of ginseng. Mutagenesis 2005; 20: 237–243.

    Article  CAS  Google Scholar 

  7. Kiefer D, Pantuso T . Panax ginseng. Am Fam Physician 2003; 68: 1539–1542.

    PubMed  Google Scholar 

  8. Kim SO, Kim MK, Lee HS, Park JK, Park K . The effect of Korean red ginseng extract on the relaxation response in isolated rabbit vaginal tissue and its mechanism. J Sex Med 2008; 5: 2079–2084.

    Article  Google Scholar 

  9. Choi HK, Seong DH, Rha KH . Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res 1995; 7: 181–186.

    CAS  PubMed  Google Scholar 

  10. Jang DJ, Lee MS, Shin BC, Lee YC, Ernst E . Red ginseng for treating erectile dysfunction: a systematic review. Br J Clin Pharmacol 2008; 66: 444–450.

    Article  CAS  Google Scholar 

  11. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY . A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol 2002; 168: 2070–2073.

    Article  CAS  Google Scholar 

  12. de Andrade E, de Mesquita AA, Claro Jde A, de Andrade PM, Ortiz V, Paranhos M et al. Study of the efficacy of Korean red ginseng in the treatment of erectile dysfunction. Asian J Androl 2007; 9: 241–244.

    Article  Google Scholar 

  13. Nah SY, McCleskey EW . Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as mu-type opioids. J Ethnopharmacol 1994; 42: 45–51.

    Article  CAS  Google Scholar 

  14. Kim HS, Lee JH, Goo YS, Nah SY . Effects of ginsenosides on Ca2+ channels and membrane capacitance in rat adrenal chromaffin cells. Brain Res Bull 1998; 46: 245–251.

    Article  CAS  Google Scholar 

  15. Kim D, Park D, Choi S, Lee S, Sun M, Kim C et al. Thalamic control of visceral nociception mediated by T-type Ca2+ channels. Science 2003; 302: 117–119.

    Article  CAS  Google Scholar 

  16. Kim S, Ahn K, Oh TH, Nah SY, Rhim H . Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 2002; 296: 247–254.

    Article  CAS  Google Scholar 

  17. Moczydlowski EG . The maxi K+ channel of human myometrium reveals a split personality. J Physiol 2006; 573: 286.

    Article  CAS  Google Scholar 

  18. Ledoux J, Werner ME, Brayden JE, Nelson MT . Calcium-activated potassium channels and the regulation of vascular tone. Physiology (Bethesda) 2006; 21: 69–78.

    CAS  Google Scholar 

  19. Lu R, Alioua A, Kumar Y, Eghbali M, Stefani E, Toro L . MaxiK channel partners: physiological impact. J Physiol 2006; 570: 65–72.

    Article  CAS  Google Scholar 

  20. Choi YD, Xin ZC, Choi HK . Effect of Korean red ginseng on the rabbit corpus cavernosal smooth muscle. Int J Impot Res 1998; 10: 37–43.

    Article  CAS  Google Scholar 

  21. Choi YD, Rha KH, Choi HK . In vitro and in vivo experimental effect of Korean red ginseng on erection. J Urol 1999; 162: 1508–1511.

    Article  CAS  Google Scholar 

  22. Kim HJ, Woo DS, Lee G, Kim JJ . The relaxation effects of ginseng saponin in rabbit corporal smooth muscle: is it a nitric oxide donor? Br J Urol 1998; 82: 744–748.

    Article  CAS  Google Scholar 

  23. Brink PR, Ramanan SV, Christ GJ . Human connexin 43 gap junction channel gating: evidence for mode shifts and/or heterogeneity. Am J Physiol 1996; 271: C321–C331.

    Article  CAS  Google Scholar 

  24. Cahn D, Melman A, Valcic M, Christ GJ . Forskolin: a promising new adjunct to intracavernous pharmacotherapy. J Urol 1996; 155: 1789–1794.

    Article  CAS  Google Scholar 

  25. Palmer LS, Valcic M, Melman A, Giraldi A, Wagner G, Christ GJ . Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells. J Urol 1994; 152: 1308–1314.

    Article  CAS  Google Scholar 

  26. Staerman F, Melman A, Spektor M, Christ GJ . On the putative mechanistic basis for intraoperative propofol-induced penile erections. Int J Impot Res 1997; 9: 1–9.

    Article  CAS  Google Scholar 

  27. Zhao W, Christ GJ . Endothelin-1 as a putative modulator of erectile dysfunction. II. Calcium mobilization in cultured human corporal smooth muscle cells. J Urol 1995; 154: 1571–1579.

    Article  CAS  Google Scholar 

  28. Lee SW, Wang HZ, Zhao W, Ney P, Brink PR, Christ GJ . Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells. Int J Impot Res 1999; 11: 189–199.

    Article  CAS  Google Scholar 

  29. Han DH, Chae MR, So I, Jung JH, Park JW, Lee SW . Effect of testosterone on potassium channel opening in human corporal smooth muscle cells. J Sex Med 2008; 5: 822–832.

    Article  CAS  Google Scholar 

  30. Brink PR, Fan SF . Patch clamp recordings from membranes which contain gap junction channels. Biophys J 1989; 56: 579–593.

    Article  CAS  Google Scholar 

  31. Attele AS, Wu JA, Yuan CS . Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999; 58: 1685–1693.

    Article  CAS  Google Scholar 

  32. Hasegawa H . Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci 2004; 95: 153–157.

    Article  CAS  Google Scholar 

  33. Fan SF, Brink PR, Melman A, Christ GJ . An analysis of the Maxi-K+ (KCa) channel in cultured human corporal smooth muscle cells. J Urol 1995; 153: 818–825.

    Article  CAS  Google Scholar 

  34. Werner ME, Zvara P, Meredith AL, Aldrich RW, Nelson MT . Erectile dysfunction in mice lacking the large-conductance calcium-activated potassium (BK) channel. J Physiol 2005; 567 (Part 2): 545–556.

    Article  CAS  Google Scholar 

  35. Kim ND, Kang SY, Kim MJ, Park JH, Schini-Kerth VB . The ginsenoside Rg3 evokes endothelium-independent relaxation in rat aortic rings: role of K+ channels. Eur J Pharmacol 1999; 367: 51–57.

    Article  CAS  Google Scholar 

  36. Kim ND, Kang SY, Park JH, Schini-Kerth VB . Ginsenoside Rg3 mediates endothelium-dependant relaxation in response to ginsenosides in rat aorta: role of K+ channels. Eur J Pharmacol 1999; 367: 41–49.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, the Republic of Korea (A080064).

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Authors and Affiliations

  1. Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    H H Sung, M R Chae & S W Lee

  2. Department of Physiology and Biophysics, Seoul National University College of Medicine, Seoul, South Korea

    I So & J-H Jeon

  3. Department of Urology, Medical School, and Institute for Medical Sciences, Chonbuk National University, and Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, Korea

    J K Park

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Correspondence to S W Lee.

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Sung, H., Chae, M., So, I. et al. Effects of ginsenoside on large-conductance KCa channels in human corporal smooth muscle cells. Int J Impot Res 23, 193–199 (2011). https://doi.org/10.1038/ijir.2011.25

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