Penile Erection Induced by Scoparone from Artemisia capillaris through the Nitric Oxide-Cyclic Guanosine Monophosphate Signaling Pathway

摘要

Purpose: The objective of this study was to evaluate the relaxant effect of scoparone from Artemisia capillaris on rabbit penilecorpus cavernosum smooth muscle (PCCSM) and to elucidate the mechanism of action of scoparone for the treatment of erectiledysfunction (ED).Materials and Methods: PCCSM that had been precontracted with phenylephrine was treated with 3 Artemisia herbs (A. princeps,A. capillaris, and A. iwayomogi) and 3 fractions (n-hexane, ethyl acetate, and n-butanol) with different concentrations (0.1, 0.5,1.0, and 2.0 mg/mL). Four components (esculetin, scopoletin, capillarisin, and scoparone) isolated from A. capillaris were alsoevaluated. The PCCSM was preincubated with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ). Cyclic nucleotides in the perfusate were measured by a radioimmunoassay. Theinteractions of scoparone with udenafil and rolipram were also evaluated.Results: A. capillaris extract relaxed PCCSM in a concentration-dependent manner. Scoparone had the highest relaxant effect onPCCSM among the 4 components (esculetin, scopoletin, capillarisin, and scoparone) isolated from the ethyl acetate fraction. Theapplication of scoparone on PCCSM pretreated with L-NAME and ODQ led to significantly less relaxation. Scoparone alsoincreased the cyclic guanosine monophosphate (cGMP) levels in the perfusate in a concentration-dependent manner.Furthermore, scoparone enhanced udenafil- and rolipram-induced relaxation of the PCCSM.Conclusions: Scoparone relaxed the PCCSM mainly by activating the nitric oxide-cGMP signaling pathway, and it may be a newpromising treatment for ED patients who do not completely respond to udenafil.