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 & 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 EM were extracted with 95% ethanol and the HDP was isolated by several chromatographic methods. The relaxant mechanism of the EM extract and the HDP was studied on isolated human cavernosal strips (HC strip).

Results: EM extract (0.1-3 mg/ml) relaxed HC strips precontracted with phenylephrine. The relaxant effect was not modified by N-nitro-L-arginine (L-NNA), ODQ, tetraethylammonium, nor glybenclamide. HDP (0.1-3 mM) relaxed HC strips precontracted with phenylephrine 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 (stored-operated Ca²⁺ channel blocker) was 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.