Ginseng saponin metabolites produced by human intestinal bacteria and the urinary and blood compounds after oral administration of Ginseng extract and its saponins in human and specific pathogen-free rats were examined in order to elucidate their metabolites absorbed from the intestines. The main metabolites of ginsenosides Rb1, Rb2, Rc, Re, and Rg1 after anaerobic incubation with fecal flora were identified as 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (I) 20-O-[alpha-L-arabinopyranosyl (1-->6)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol (II), 20-O-[alpha-L- arabinofuranosyl(1-->6)-beta-D-glucopyranosyl]-20(S)-protopanaxadiol+ ++ (III), and 20(S)-protopanaxatriol (IV), though the metabolic rate and mode were affected by fermentation media. Furthermore, metabolites I-IV and 20(S)-protopanaxadiol (XII) were detected in blood (0.3-5.1 micrograms/ml) and in urine (2.2-96 micrograms/ day) after the oral administration of Ginseng extract (150 mg/ kg/day) to human and of total saponin (1 g/kg/day) to rats.

Examined in vitro were the effects of some triterpenoids from Panax (Araliaceae) and Glycyrrhiza (Leguminosae) spp. on the sensitivity to daunomycin (DAU) and vinblastine (VBL) of adriamycin (ADM)-resistant P388 leukemia cells (P388/ADM), which were resistant to multiple anticancer drugs. Quasipanaxatriol, 20(S)-protopanaxatriol, ginsenoside Rh2, and compound K greatly enhanced the cytotoxicity of the anti-cancer drugs in P388/ADM cells. The extent of enhancement was different among the triterpene compounds; the 4- to 46-fold increase in DAU cytotoxicity was observed in P388/ADM cells in the presence of non-toxic or marginally toxic concentrations of individual compounds, while those for VBL were in the ratios of 2- to 37-fold. The maximum increase in cytotoxicity was observed with 50 microM quasipanaxatriol; the resistance indices defined to be the ratios of the IC50 values for P388/ADM and P388 parental cells decreased from 79 to 1.7 and from 180 to 4.9 in the cases of DAU and VBL, respectively. The reversal of DAU resistance in P388/ADM by quasipanaxatriol could be explained by the effective accumulation of the drugs mediated by the DAU-efflux blockage.

The effects of Panax ginseng extract, ginseng saponins, and some other triterpenoid saponins on glucose uptake were examined by using sheep erythrocytes. Initial rates of glucose transport were determined by measurements of 2-deoxy-D-glucose (2-DG) uptake. From kinetic analysis apparent Km and Vmax values of facilitated glucose transport in sheep erythrocytes were calculated as 2.3 +/- 0.08 mM and 1.4 +/- 0.05 nmol/min/10(9) cells. The results showed that ginseng extract stimulated glucose uptake in sheep erythrocytes dose-dependently. Ginseng saponins, in general, also stimulated glucose transport. The maximum effect was observed at 1 microM of ginsenoside Rb1 showing an increase of 24 +/- 5% above basal activity. However, ginsenoside Rg3, chikusetsusaponin Ia, and glycyrrhetic acid induced significant inhibitory effects on glucose transport in sheep erythrocytes.

The effects of some triterpenoid saponins on glucose transport in Ehrlich ascites tumor (EAT) cells were examined by measuring 2-deoxy-D-glucose (2-DG) uptake. The correlation of the effects with those on the growth of a human T-cell line (MT-4) and the replication of human immunodeficiency virus in MT-4 cells was also studied. Chikusetsusaponin Ia isolated from rhizomes of Panax japonicus C. A. Meyer (Araliaceae) inhibited the 2-DG uptake (IC50 = 76.3 microM) in a competitive fashion with respect to 2-DG (Ki = 0.32 mM) and the growth of MT-4 cells with CC50 of 84.4 microM, whereas it did not show any significant anti-HIV-1 activity. In contrast, zingibroside R1 isolated from rhizomes of Panax zingiberensis Wu et Feng (Araliaceae) showed some anti-HIV-1 activity, which was found to be superior to that of glycyrrhizin, as well as the inhibitory effects on the 2-DG uptake by EAT cells (IC50 = 91.3 microM) and the growth of MT-4 cells (CC50 = 46.2 microM).

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