9-Hydroxycanthin-6-One Induces Penile Erection and Delays Ejaculation

Introduction. Eurycoma longifolia Jack (Simaroubaceae) has the reputation as a male aphrodisiac because it is claimed to increase virility and sexual prowess. Nevertheless, whether or not E. longifolia regulates directly the muscle tone of corpus cavernosa and/or seminal vesicle (SV) remains unclear. Even until now, the compositions that could account for its aphrodisiac property are still unknown Aim. We examined the effect of 9-hydroxycanthin-6-one (9-HC-6-one), a β-carboline alkaloid isolated from E. longifolia, on penile erection and ejaculation, and further elucidated the mechanism of action. Main Outcome Measures. 9-HC-6-one induces penile erection and delays ejaculation. Methods. Drug's effect was studied on rat corpus cavernosum (CC) and SV in vitro, and on the changes in intracavernosal pressure (ICP) after IC injection and intraluminal pressure (ILP) of the SV after hypogastric nerve stimulation (HNS), respectively. Results. 9-HC-6-one relaxed significantly phenylephrine (PE)-precontracted CC. Such response was not attenuated by endothelium disruption, N^G-nitro-L-arginine methyl ester, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one treatment, suggesting that a nitric oxide/cyclic guanosine monophosphate-dependent pathway was precluded. 9-HC-6-one attenuated PE-induced contraction by blocking cell surface and internal calcium channels with a higher potency for internal calcium release. This compound also antagonized calcium-evoked contraction in Ca²⁺-free, high K⁺-depolarizing condition, suggesting that interfering with the entry of calcium through voltage-dependent channels also contributed to 9-HC-6-one-induced corporal relaxation. After IC application of 9-HC-6-one, a significant rise in ICP was observed as compared with the application of normal saline. 9-HC-6-one relaxed significantly norepinephrine (NE)- and KCl-precontracted SV, and antagonized NE-induced oscillatory contraction as potent as clomipramine. Finally, the HNS-evoked increase in ILP was dose-dependently repressed after challenge by 9-HC-6-one. Conclusion. 9-HC-6-one might be the active component that contributed to the aphrodisiac effect of E. longifolia by antagonizing the smooth muscle tone of CC as well as SV probably through interfering with Ca²⁺ mobilization.