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Beneficial Effect of Berberis amurensis Rupr. on Penile Erection

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Abstract

Objective

To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.

Methods

The ex vivo study used corpus cavernosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats.

Results

Preconstricted with phenylephrine (PE) in isolated endotheliumintact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-1-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P<0.01), a nonselective K+ channel blocker, 4-aminopyridine (4-AP, P<0.01), a voltage-dependent K+ channel blocker, and charybdotoxin (P<0.01), a large and intermediate conductance Ca2+ sensitive-K+ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently.

Conclusion

BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2+ sensitive-K+ (BKCa and IKCa) channels in the corpus cavernosum.

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References

  1. Toda N, Ayajiki K, Okamura T. Nitric oxide and penile erectile function. Pharmacol Ther 2005;106:233–266.

    Article  PubMed  CAS  Google Scholar 

  2. Priviero FB, Leite R, Webb RC, Teixeira CE. Neurophysiological basis of penile erection. Acta Pharmacol Sin 2007;28:751–755.

    Article  PubMed  CAS  Google Scholar 

  3. Gilotti AC, Nimlamool W, Pugh R, Slee JB, Barthol TC, Miller EA, et al. Heparin responses in vascular smooth muscle cells involve cGMP-dependent protein kinase (PKG). J Cell Physiol 2014;229:2142–2152.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Martínez-Salamanca JI, La Fuente JM, Cardoso J, Fernández A, Cuevas P, Wright HM, et al. Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway. J Sex Med 2014;11:1182–1192.

    Article  PubMed  CAS  Google Scholar 

  5. Dhir RH, Lin HC, Canfield ES, Wang R. Combination therapy for erectile dysfunction: an update review. Asian J Androl 2011;13:382–390.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Sun K, Zhao C, Chen FX, Kim HK, Choi BR, Huang YR, et al. Ex vivo relaxation effect of Cuscuta chinensis extract on rabbit corpus cavernosum. Asian J Androl 2013;15:134–137.

    Article  PubMed  Google Scholar 

  7. Frajese GV, Pozzi F. Phosphodiesterase type 5 inhibithors in older males. J Endocrinol Invest 2005;28:112–115.

    PubMed  CAS  Google Scholar 

  8. Prieto D. Physiological regulation of penile arteries and veins. J Impot Res 2008;20:17–29.

    Article  CAS  Google Scholar 

  9. Félétou M. Calcium-activated potassium channels and endothelial dysfunction: therapeutic options. Br J Pharmacol 2009;156:545–562.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Novakovic R, Ilic B, Beleslin-Cokic B, Radunovic N, Heinle H, Scepanovic R, et al. The effect of resveratrol on contractility of non-pregnant rat uterus: the contribution of K+ channels. J Physiol Pharmacol 2013;64:795–805.

    PubMed  CAS  Google Scholar 

  11. Sukrittanon S, Watanapa WB, Ruamyod K. Ginsenoside Re enhances small-conductance Ca(2+)-activated K(+) current in human coronary artery endothelial cells. Life Sci 2014;115:15–21.

    Article  PubMed  CAS  Google Scholar 

  12. Siehr SL, McCarthy EK, Ogawa MT, Feinstein JA. Reported sildenafil side effects in pediatric pulmonary hypertension patients. Front Pediatr 2015;9:3–12.

    Google Scholar 

  13. Yusupov MM, Karimov A, Shakirov R, Gorovoi PG. An investigation of the alkaloids of Berberis amurensis. Plenum Publishing Corporation Chem Nat Compound 1993;29:338.

    Article  Google Scholar 

  14. Tomita M, Kugo T. The alkaloids: chemistry and physiology. J Am Chem Soc 1955;77:253–253.

    Google Scholar 

  15. Thornber CW. Alkaloids of the menispermaceae. Phytochemistry 1970;9:157–187.

    Article  CAS  Google Scholar 

  16. Xiao HJ, Wang T, Chen J, Fan LC, Yin CP, Liu JH, et al. Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits. Int J Impot Res 2010;22:120–126.

    Article  PubMed  Google Scholar 

  17. Pankey EA, Lasker GF, Gur S, Hellstrom WG, Kadowitz PJ, et al. Analysis of erectile responses to imatinib in the rat. Urology 2013;253:17–24.

    Google Scholar 

  18. Burnett AL. The role of nitric oxide in erectile dysfunction: implications for medical therapy. J Clin Hypertens (Greenwich) 2006;8:53–62.

    Article  CAS  Google Scholar 

  19. Rstermann UF, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33:829–837.

    Article  CAS  Google Scholar 

  20. Moreland RB, Hsieh G, Nakane M, Brioni JD. The biochemical and neurologic basis for the treatment of male erectile dysfunction. J Pharmacol Exp Ther 2001;296:225–234.

    PubMed  CAS  Google Scholar 

  21. Valtcheva N, Nestorov P, Beck A, Russwurm M, Hillenbrand M, Weinmeister P, et al. The commonly used cGMP-dependent protein kinase type I (cGKI) inhibitor Rp-8-Br-PET-cGMPS can activate cGKI in vitro and in intact cells. J Biol Chem 2009;284:556–562.

    Article  PubMed  CAS  Google Scholar 

  22. Yildiz O, Seyrek M, Irkilata HC, Yildirim I, Tahmuz L, Dayanc M, et al. Testosterone might cause relaxation of human corpus cavernosum by potassium channel opening action. Urology 2009;74:229–232.

    Article  PubMed  Google Scholar 

  23. Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev 2011;63:811–859.

    Article  PubMed  CAS  Google Scholar 

  24. Wu BN, Chen CF, Hong YR, Howng SL, Lin YL, Chen IJ, et al. Activation of BKCa channels via cyclic AMP-and cyclic GMP-dependent protein kinases by eugenosedin-A in rat basilar artery myocytes. Br J Pharmacol 2007;152:374–385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Khan LH, Rosenfeld CR, Liu XT, Magness RR. Regulation of the cGMP-cPKG pathway and large-conductance Ca2+-activated K+ channels in uterine arteries during the ovine ovarian cycle. Am J Physiol Endocrinol Metab 2010;298:E222–E228.

    Article  PubMed  CAS  Google Scholar 

  26. Mamo YA, Angus JA, Ziogas J, Soeding PF, Wright CE. The role of voltage-operated and non-voltage-operated calcium channels in endothelin-induced vasoconstriction of rat cerebral arteries. Eur J Pharmacol 2014;742:65–73.

    Article  PubMed  CAS  Google Scholar 

  27. Lin CS, Liu X, Chow S, Lue TF. Cyclic AMP and cyclic GMP activate protein kinase G in cavernosal smooth muscle cells: old age is a negative factor. BJU Int 2002;89:576–582.

    Article  PubMed  CAS  Google Scholar 

  28. Andersson KE. Pharmacology of penile erection. Pharmacol Rev 2001;53:417–450.

    PubMed  CAS  Google Scholar 

  29. Sobrino A, Mata M, Laguna-Fernandez A, Novella S, Oviedo PJ, García-Pérez MA, et al. Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells. PLoS One 2009;4:e8242.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Zhou L, Chen Z, Vanderslice P, So SP, Ruan KH, Willerson JT, et al. Endothelial-like progenitor cells engineered to produce prostacyclin rescue monocrotaline-induced pulmonary arterial hypertension and provide right ventricle benefits. Circulation 2013;128:982–994.

    Article  PubMed  CAS  Google Scholar 

  31. Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 1987;92:181–187.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Luedders DW, Muenz BM, Li F, Rueckleben S, Tillmanns H, Waldecker B, et al. Role of cGMP in sildenafil-induced activation of endothelial Ca2+-activated K+ channels. J Cardiovasc Pharmacol 2006;47:365–370.

    PubMed  CAS  Google Scholar 

  33. Bischoff E, Schramm M, Straub A, Feurer A, Stasch JP. BAY 41-2272: a stimulator of soluble cyclase induces nitric oxide-dependent penile erection in vivo. Urology 2003;61:464–467.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 570-749, Republic of Korea

    Rui Tan, Yun Jung Lee, Dae Gill Kang & Ho Sub Lee

  2. Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea

    Yun Jung Lee, Kyung Woo Cho, Dae Gill Kang & Ho Sub Lee

  3. Brain Korea 21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea

    Dae Gill Kang & Ho Sub Lee

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  1. Rui Tan
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Correspondence to Ho Sub Lee.

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Tan, R., Lee, Y.J., Cho, K.W. et al. Beneficial Effect of Berberis amurensis Rupr. on Penile Erection. Chin. J. Integr. Med. 24, 448–454 (2018). https://doi.org/10.1007/s11655-017-2920-z

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  • DOI: https://doi.org/10.1007/s11655-017-2920-z

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