Relaxation of corpus cavernosum and raised intracavernosal pressure by extract of Panax ginseng in rabbit / 人參抽提物對大白兔離體及活體陰莖海綿體的舒張活性評估

碩士 / 國立陽明大學 / 藥理學研究所 / 88 / Ginseng has been used for thousands of years in China as a general health tonic for improvement of physiological functions including penile erection. The present study was undertaken to investigate the potential beneficial effects of red ginseng (RG) on erectile dysfunction through its effects on isolated rabbit corpus cavernosum and inracavernosal pressure (ICP). RG was extracted by refluxing with 60%EtOH and concentrated in vacuo. Ethanolic extract was further disolved in water and partitioned between ether and the aqueous layers, and the aqueous layer was then extracted with BuOH saturated with water. Our result demonstrated that EtOH crude extract, n-BuOH extract and H2O extract induced potent relaxant effects on phenylephrine (PE)-precontracted corpus cavernosal strips with ED50 of 3.4±0.4, 2.7±0.4 and 4.0±0.6 mg/ml, respectively. In anesthetized rabbit, intracavernosal injection of n-BuOH extract (40 and 100 mg/kg) also induced dose-dependent sustained increase in ICP. Among 9 fractions (GF1-GF9) obtained from n-BuOH extract on a column of silica gels eluted with a gradient of CH2Cl2: MeOH (100:0→0:100), the GF3 fraction possessed the most potent dose-dependent (0.5-12 mg/ml) corporal relaxant effect (ED50=1.7±0.3mg/ml). The ginsenosides contained in GF3 were Rg1, Rf and Rc. Comparison of the relaxant potencies between GF3 and Rg1 (3, 6, and 9 mg/ml) indicated that the former was more potent in relaxing corporal cavernosal strips (86.1±7.4, 100, and 100 %) vs. (0, 11.7±6.9, and 15.5±0.3 %). Removal of the endothelium had no significant effect on the GF3-induced relaxation. Addition of the NO synthase inhibitor L-NG-nitro arginine methyl ester (0.3mM) and soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (30mM) abolished acetylcholine- and sodium nitroprusside-induced corporal relaxation but did not affect the GF3-evoked response. Indomethacin (30mM) and propranolol (1mM) treatment also did not inhibit the GF3-induced corporal relaxation. The above findings indicated that components other than Rg1 might account for the potent corporal relaxant effect of GF3, and the corporal relaxant effect of GF3 appeared to be endothelium-, NO-cGMP-, prostaglandin E- and b-adrenoceptors-independent. Like cromakalim (K+ -channel opener), GF3 (1.5 and 3 mg/ml) caused a complete and dose-dependent relaxation of corporal cavernosal strips contracted with PE but failed to inhibit completely the contractile effects of 80mM KCl. GF3 induced relaxation was decreased as the extracellular potassium concentration was increased from 4.7mM to 80mM. Moreover, GF3 evoked corporal relaxation was suppressed by tetrabutylammonium chloride and tetraethylammonium chloride (non-selective K+-channel blocker, 10mM). The contractile response to histamine was also attenuated by GF3 (1.5 and 3mg/ml) and triprolidine (H1 receptor antagonist, 0.1 to 50μM). These findings suggested that some active component(s) other than Rg1 might be responsible for the beneficial corporal relaxant effect of GF3. A hyperpolarizing effect via potassium channel opening and antagonism of H1 receptor might be related to this effect. Detailed mechanisms of action and characterization of the therapeutic potential for erectile dysfunction warrant and await further investigations.

Identiferoai:union.ndltd.org:TW/088YM000550003
Date January 2000
CreatorsWoan- Ching Jan, 詹婉卿
ContributorsChieh- Fu Chen, 陳介甫
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format68

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