Effects of Korean ginseng berry extract (GB0710) on penile erection: evidence from in vitro and in vivo studies

Abstract

Several reports have promoted the root-derived Korean red ginseng (KRG; Panax ginseng) as alternative treatment for erectile dysfunction (ED), and ginsenosides are known to be the principal active ingredients of ginseng. Recent studies showed that ginseng berries produce more ginsenosides than KRG; thus, we investigated the ability of the Korean ginseng berry extract GB0710 to relax the penile corpus cavernosum smooth muscle (CCSM) in this study. As a comparative control, the results were compared to those obtained using KRG. In addition, possible mechanisms of action for GB0710 were investigated. While KRG and GB0710 both displayed dose-dependent relaxation effects on precontracted rabbit CCSM in vitro, GB0710 was shown to be more potent than KRG. The GB0710-induced relaxation could be partially reduced by removing the endothelium. In addition, pre-treatment with several nitric oxide (NO) inhibitors significantly inhibited the relaxation of muscle strips. Furthermore, administration of GB0710 increased intracavernosal pressure (ICP) in a rat in vivo model in both a dose- and duration-dependent manner. Intracellular NO production in human microvascular endothelial cells could be induced by GB0710 and inhibited by N(G)-monomethyl-L-arginine. In conclusion, GB0710 had a greater relaxation effect on rabbit CCSM than did KRG extract, and increased ICP in a rat model in both a dose- and a duration-dependent manner. This relaxing effect might be mediated by NO production.

Figure 1

Percentage weight of the seven ginsenosides in GB0710 and KRG extract obtained by high-performance liquid chromatography analysis. KRG, Korean red ginseng; Rb1, ginsenoside-Rb1 (C₅₄H₉₂O₂₃); Rb2, ginsenoside-Rb2 (C₅₃H₉₀O₂₂); Rc, ginsenoside-Rc (C₅₃H₉₀O₂₂); Rd, ginsenoside-Rd (C₄₈H₈₂O₁₈); Re, ginsenoside-Re (C₄₈H₈₂O₁₈); Rg1, ginsenoside-Rg1 (C₄₂H₇₂O₁₄); Rg2, ginsenoside-Rg2 (C₄₂H₇₂O₁₃).

Figure 2

(a) Effects of both GB0710 and KRG extract on the isolated rabbit corpus cavernosum smooth muscle strips submaximally precontracted by phenylephrine (5×10⁻⁶ mol l⁻¹). The relaxation effect showed a dose-dependent relaxation, but the relaxation effect of GB0710 was higher than KRG extract. Values are represented as mean±standard error and expressed as percentage of the relaxation. (b) Representative graphs of GB0710 effects on the isolated rabbit corpus cavernosal smooth muscle strip precontracted by phenylephrine (5×10⁻⁶ mol l⁻¹). *P<0.05, the difference between treatment and control by Mann–Whitney U test; ^†P<0.05, the difference between GB0710 treatment and that of KRG treatment at the same concentrations by Mann–Whitney U test. KRG, Korean red ginseng.

Figure 3

Effects of various treatments on GB0710-induced relaxation in the phenylephrine (5×10⁻⁶ mol l⁻¹)-induced precontracted rabbit isolated corpus cavernosum smooth muscle strip. The relaxation effect of GB0710 was partially inhibited by endothelial disruption and by pretreatment with methylene blue (10⁻⁴ mol l⁻¹), pyrogallol (10⁻⁴ mol l⁻¹), L-NNA (3×10⁻⁴ mol l⁻¹), or 1H-[1,2,4] ODQ (5×10⁻⁶ mol l⁻¹). Values are represented as mean±standard error and expressed as percentage of the relaxation. *P<0.05, the difference between treatment and control by Mann–Whitney U test. L-NNA, N^G-nitro-L-arginine; ODQ, oxadiazolo-[4, 3-α] quinoxalin-1-one.

Figure 4

Intracavernosal pressure with cavernosal nerve stimulation after long-term administration of GB0710. After administration of GB0710 at doses of 20, 40, 100 and 150 mg, intracavernosal pressure increased in a dose- and duration-dependent fashion. *P<0.05, the difference between treatment and control by Mann–Whitney U test; ^†P<0.05, the difference among various groups at the same concentrations of each treatment by Kruskal–Wallis test.

Figure 5

GB0710 induced intracellular NO production in HMVECs. (a) HMVECs were treated with GB0710 (200 µg ml⁻¹) or KRG (200 µg ml⁻¹) in the presence or absence of L-NMMA (2 mmol l⁻¹) for 30 min, followed by incubation with DAF-FM/DA (10 µmol l⁻¹) for 1 h. Intracellular NO levels were determined by confocal microscopy. (b) The relative levels of NO were calculated from fluorescence intensities. *P<0.05, the difference between treatment and control by Mann–Whitney U test. DAF-FM/DA, 4-amino-5-methylamino-2,7-difluorofluorescein diacetate; HMVEC, human microvascular endothelial cell; KRG, Korean red ginseng; L-NMMA, N^G-monomethyl-L-arginine; NO, nitric oxide.