Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway


Epimedium brevicornum Maxim (EbM) has been reputed to have sexual stimulation effects on males. The study is aimed to test the hypothesis that EbM extracts relaxed the corpus cavernosum (CC) smooth muscle through activation of multitargets on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway. Water extract of EbM and its subfraction (EP-20) were prepared and standardized by high-performance liquid chromatography. Isolated rabbit CC strips were mounted in organ baths and isometric tension was recorded in the presence or absence of specific inhibitors related to NO/cGMP signaling such as L-NG-nitro-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ, a guanylyl cyclase inhibitor) or phosphodiesterase 5 (PDE 5) inhibitors. cGMP level was determined in EP-20-treated CC strips. The results showed that EP-20 enriched the content of L-arginine in the process of purification and relaxed the CC smooth muscle precontracted with phenylephrine (PE, 1 μ M) in a concentration-dependent manner. Besides, EP-20 increased the amount of cGMP production in rabbit CC tissues. Coincubation with EP-20 and L-NAME or ODQ significantly decreased EP-20-induced relaxation whereas EP-20 increased sodium nitroprusside-induced relaxation in PE-precontracted CC strips. Besides, EP-20 increased the potency and the duration of the relaxation effects caused by electrical field stimulation. Finally, EP-20 could potentiate PDE 5 inhibitors in relaxation of PE-precontracted CC strips. We concluded that extract of EbM relax the CC smooth muscle through multitargets in NO/cGMP/PDE 5 pathway and might bring into perspective the treatment strategy for those patients with erectile dysfunction.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6


  1. Nehra A, Moreland RB . Neurologic erectile dysfunction. Urol Clin North Am 2001; 28: 289–308.

    CAS  Article  Google Scholar 

  2. Mills TM . Vasoconstriction and vasodilation in erectile physiology. Curr Urol Rep 2002; 3: 477–483.

    Article  Google Scholar 

  3. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA . Oral sildenafil in the treatment of erectile dysfunction. N Eng J Med 1998; 338: 1397–1404.

    CAS  Article  Google Scholar 

  4. Chen KK, Hsieh JT, Huang ST, Jiaan DB, Lin JS, Wang CJ . ASSESS-3: a randomised, double-blind, flexible-dose clinical trial of the efficacy and safety of oral sildenafil in the treatment of men with erectile dysfunction in Taiwan. Int J Imptot Res 2001; 13: 221–229.

    CAS  Article  Google Scholar 

  5. Hellstrom WJ, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T et al. Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial. J Androl 2002; 23: 763–771.

    CAS  Google Scholar 

  6. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280: 1569–1575.

    CAS  Article  Google Scholar 

  7. Eisenberg DM, Cohen MH, Hrbek A, Grayzel J, Van Rompay MI, Cooper RA . Credentialing complementary and alternative medical providers. Ann Int Med 2002; 137: 965–973.

    Article  Google Scholar 

  8. Normile D . The new face of traditional Chinese medicine. Science 2003; 299: 188–190.

    CAS  Article  Google Scholar 

  9. Wu H, Lien EJ, Lien LL . Chemical and pharmacological investigations of Epimedium species: a survey. Prog Drug Res 2003; 60: 1–57.

    CAS  PubMed  Google Scholar 

  10. Ye LC, Chen JM . Advances in study on pharmacological effects of Epimedium. Zhongguo Zhong Yao Za Zh 2001; 26: 293–295.

    CAS  Google Scholar 

  11. Chai Y, Ji S, Zhang G, Wu Y, Yin X, Liang D et al. Determination of icariin in Chinese traditional medicine by capillary zone electrophoresis. Biomed Chromatogr 1999; 13: 373–375.

    CAS  Article  Google Scholar 

  12. Du Q, Xia M, Ito Y . Purification of icariin from the extract of Epimedium segittatum using high-speed counter-current chromatography. J Chromatogr A 2002; 962: 239–241.

    CAS  Article  Google Scholar 

  13. Tsai TH . Assaying protein unbound drugs using microdialysis techniques [Review]. J Chromatogr B 2003; 797: 161–173.

    CAS  Article  Google Scholar 

  14. Cohen SA, De Antonis KM . Applications of amino acid derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Analysis of feed grains, intravenous solutions and glycoproteins. J Chromatogr A 1994; 661: 25–34.

    CAS  Article  Google Scholar 

  15. Chiou WF, Chen CF . Pharmacological profile of evodiamine in isolated rabbit corpus cavernosum. Eur J Pharmacol 2002; 446: 151–159.

    CAS  Article  Google Scholar 

  16. Huang YT, Lo JW, Lin HC, Tsai YT, Hong CY, Yang CM . Change in vascular cAMP and cGMP contents in portal hypertensive rats. Pharmacology 1995; 50: 86–91.

    CAS  Article  Google Scholar 

  17. Bennett NE, Kim JH, Wolfe DP, Sasaki K, Yoshimura N, Goins WF et al. Improvement in erectile dysfunction after neurotrophic factor gene therapy in diabetic rats. J Urol 2005; 173: 1820–1824.

    CAS  Article  Google Scholar 

  18. Chen KK, Chan JY, Chang LS, Chen MT, Chan SH . Elicitation of penile erection following activation of the hippocampal formation in the rat. Neurosci Let 1992; 141: 218–222.

    CAS  Article  Google Scholar 

  19. Christ GJ, Day N, Santizo C, Sato Y, Zhao W, Sclafani T et al. Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo. Am J Physiol Heart Circ Physiol 2004; 287: H1544–H1553.

    CAS  Article  Google Scholar 

  20. Lau DH, Kommu S . Relaxation effects of adrenomedullin in isolated rabbit corpus cavernosum smooth muscle. BJU Int 2004; 94: 446–447.

    Article  Google Scholar 

  21. Muneer A, Cellek S, Dogan A, Kell PD, Ralph DJ, Minhas S . Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model. Int J Impot Res 2005; 17: 10–18.

    CAS  Article  Google Scholar 

  22. Shukla N, Jones R, Persad R, Angelini GD, Jeremy JY . Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits. Eur J Pharmacol 2005; 11: 224–231.

    Article  Google Scholar 

  23. Paick JS, Lee JH . An experimental study of the effect of ginkgo biloba extract on the human and rabbit corpus cavernosum tissue. J Urol 1996; 156: 1876–1880.

    CAS  Article  Google Scholar 

  24. Dunzendorfer U, Behm A, Dunzendorfer E, Dunzendorfer A . Drug combinations in the therapy of low response to phosphodiesterase 5 inhibitors in patients with erectile dysfunction. In vivo 2002; 16: 345–348.

    CAS  PubMed  Google Scholar 

  25. Dell'Agli M, Galli GV, Vrhovsek U, Mattivi F, Bosisio E . In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes. J Agric Food Chem 2005; 23: 1960–1965.

    Article  Google Scholar 

Download references


This work was supported by a grant from Veterans General Hospital, Taipei (VGH93-349 and VGH94-362-3).

Author information

Authors and Affiliations


Corresponding author

Correspondence to J-H Chiu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chiu, JH., Chen, KK., Chien, TM. et al. Epimedium brevicornum Maxim extract relaxes rabbit corpus cavernosum through multitargets on nitric oxide/cyclic guanosine monophosphate signaling pathway. Int J Impot Res 18, 335–342 (2006).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • erectile dysfunction
  • Epimedium brevicornum
  • organ bath
  • cGMP
  • PDE 5

Further reading


Quick links