Relaxant mechanism of Eulophia macrobulbon ethanolic extract and 1-(4΄-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol on human corpus cavernosum

Abstract

Background: Eulophia macrobulbon (E.C.Parish and Rchb.f.) Hook.F. has been shown to be a promising phosphodiesterase-5 (PDE5) inhibitor that relaxes rat isolated pulmonary artery. Objective: To test this plant’s possible application in human erectile dysfunction (ED) using an ethanolic extract of E. macrobulbon tubers (EM extract), and an isolated constituent, 1-(4΄-hydroxybenzyl)-4,8-dimethoxyphenanthrene-2,7-diol (HDP). Methods: Dried tubers of E. macrobulbon (EM) were extracted with 95% ethanol and the HDP was isolated by open column chromatography and high-performance liquid chromatography (HPLC) methods. The relaxant mechanism of the EM extract and the HDP was studied on isolated human cavernosal (HC) strips. Results: EM extract relaxed HC strips, and this effect was not modified by NG-nitro-L-arginine (L-NNA), ODQ, tetraethylammonium, nor glybenclamide. HDP relaxed HC strips to the same extent as that of sildenafil. EM extract and HDP potentiated relaxation of the HC strips to glyceryl trinitrate in a similar manner to that of sildenafil. EM extract and sildenafil, but not HDP, increased cGMP content of the HC strips in a concentration-dependent manner. In the thapsigargin-pretreated HC strips, nifedipine or EM extract, but not HDP, suppressed the contractile response of the HC strips to phenylephrine. When nifedipine and/or SKF 96365 were added, followed by EM extract or HDP, further suppression was found in the case of HDP but not with EM extract. Ca2+ free Krebs solution, suppressed the phenylephrine contraction on HC strips and further suppression was found when adding EM extract or HDP. Conclusion: These results indicate that EM extract causes a relaxation of HC strips by serving as an inhibitor of PDE5, of voltage- and stored-operated Ca2+channels, and of intracellular Ca2+ mobilization. Thus, EM extract might be a good choice for development as a functional food for erectile dysfunction in men. However, further studies are needed to identify other PDE5 and the Ca2+channel inhibiting components of the extract.