Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro

Purpose: We investigated the cavernosal relaxant effect of osthole, a coumarin isolated from Cnidium monnier (L.) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction. Materials and Methods: Strips of rabbit corpus cavernosum were precontracted with phenylephrine. Corporal relaxation evoked by osthole was then determined in the absence and presence of nitric oxide synthase inhibitor (L-NAME), soluble guanylate cyclase inhibitor (ODQ), cyclooxygenase inhibitor (indomethacin), tetradotoxin, and after endothelium deprivation. Results: Corpus cavernosal strips showed relaxation in response to osthole (0.1 similar to 30 mu M) in a dose-dependent manner. These effects were reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption. However, they were not affected by indomethacin and tetradotoxin treatment. Osthole pretreatment (from 1 to 30 mu M) enhanced the sodium nitroprusside (0.3 mu M)-induced relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 mu M osthole. However, this effect was abolished in the presence of zaprinast. Additionally, a higher concentration of osthole (30 mu M) also enhanced forskolin-induced relaxation. Conclusion: The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase.