Comparison of Endothelium-Dependent Vasorelaxation of Crude Ginsenosides from Mountain-Grown Ginseng and Red Ginseng

Abstract

Mountain-grown ginseng (Panax ginseng C. A. Meyer; Sansam in Korean) is believed to possess more potent biological activity than red ginseng. This study examined the endothelium-dependent vasorelaxant effects and possible mechanisms of crude ginsenosides from adventitious roots of Korean mountain-grown ginseng (GS-ARMG) and red ginseng (GS-RG) in isolated rat aorta pre-contracted with norepinephrine. GS-ARMG (0.03–3.0 mg/mL) produced transient acute relaxation in a concentration-dependent manner, with a maximum relaxation (mean ± SEM) of 90 ± 9% and a median effective concentration (EC50) of 0.09 ± 0.07 mg/mL. GS-ARMG displayed about 25-fold more potent activity than GS-RG (maximum relaxation 50 ± 4%, EC50 2.34 ± 1.30 mg/mL). Relaxations induced by both GS-ARMG (1.0 mg/mL) and GS-RG (1.0 mg/mL) were nearly abolished by endothelial ablation or pre-treatment with N G -nitro-l-arginine, a nitric oxide synthase inhibitor, or by methylene blue, a soluble guanylate cyclase inhibitor. These inhibitory effects, however, revealed different sensitivity of GS-ARMG and GS-RG; the maximum relaxations attained were 30–38% and 13–17% that of untreated preparations, respectively, but indomethacin and cyclooxygenase inhibitors did not affect the response. None of the receptor antagonists, atropine, diphenhydramine, [D-Pro2, D-Trp7, 9]-substance P, or propranolol, caused any significant inhibition to GS-ARMG-induced relaxation; however, atropine or propranolol caused a 10% reduction in the relaxation, suggesting possible involvement of a muscarinic receptor or a β-adrenoceptor in the GS-ARMG-induced relaxation. These results demonstrate that GS-ARMG produces endothelium-dependent relaxation of isolated rat aorta similar to that of GS-RG; increased nitric oxide production and increased vascular levels of cGMP in endothelial cells could contribute to the relaxation. However, GS-ARMG has more potent activity than GS-RG to relax isolated rat aorta though an active substance(s), which might be higher in mountain-grown ginseng due to the growing conditions on mountains or the processing during manufacture of GS-ARMG. These factors may contribute to understanding the biological beneficial effects of mountain-grown ginseng.