Protopanaxatriol

Furthermore, in a recent study by Takei and colleagues, the ginsenoside metabolites Ml (Compound K) and M4 (20(S)-Protopanaxatriol) were demonstrated to promote the maturation of human monocyte-derived DCs [48], M4, and to a lesser extent Ml, increased the DC expression of key costimulatory molecules, decreased their endocytic activity, and induced their production of IL-12. Moreover, these effects had the end result of generating mature DCs that could induce potent Thl polarization. Unfortunately, it was not clearly defined in this study if the ginsenoside metabolites were used at physiologically relevant concentrations, a variable that would be expected to have significant implications on the interpretation of these results. 

FIGURE 1.3 Possible metabolism (degradation pathway) of protopanaxatriol-type ginsenosides such as ginsenoside Rg, and Re by stomach acidity and by human intestinal bacteria. 

FIGURE 1.5 Possible biosynthetic route for ginsenosides of the dammarenediol-, protopanaxadiol-, and protopanaxatriol-type via dammarenediol. 

Cui, J.-F., Bjorkhem, 1., and Eneroth, P. (1997). Gas chromatographic-mass spectrometric determination of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol for study on human urinary excretion of ginsenosides after ingestion of ginseng preparations. /. Chromatogr. B 689, 349-355. 

Hasegawa, H., Suzuki, R., Nagaoka, T., Tezuka, Y., Kadota, S., and Saiki, I. (2002). Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol. Pharm. Bull. 25, 861-866. 

Kang, S. Y., Schini-Kerth, V. B., and Kim, N. D. (1995b). Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta. Life Sci. 56,1577-1586. 

Sun, H., Yang, Z., and Ye, Y. (2006). Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng. Int. Immunopharmacol. 6,14-25. 

Fig. 2.2 Structures of common ginsenosides. The core damarane structure common to ginsenosides is shown along with the carbon skeletons of the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol ginsenosides. The sugar decorations of the most common ginsenosides are indicated in the table below the structures. Legend Ara(/), arabinose (furanose form) Ara(p), arabinose (pyranose form) Glc, glucose...

Fig. 5.1 Chemical structures of ginsenosides. Ginsenosides can be separated into protopanaxadi-ols (a) or protopanaxatriols (b), depending on the presence or absence of a substituent group at carbon 6. Individual ginsenosides differ according to their sugar moieties, as indicated by Ri and R2 in the table...

A study we performed with mini pigs in cooperation with the University of Zurich30 showed, after intravenous administration, that the derivatives of protopanaxatriol, as Rglr have a one compartment pharmacokinetic profile, and a half-life of about 30 min. Whereas for the derivatives of protopanaxadiol, such as Rbj, the half-life is much longer, about 16 h, and its pharmacokinetics is described with a two-compartment model (Figure 16.30). 

Figure 1. The Major Ginsenosides of Panax spp. The three main triterpenoid aglycones (20S)-protopanaxadiol, (20S)-protopanaxatriol, oleanoic acid), as well as the six major ginsenosides of Panax spp. are shown. Ginsenosides are named according to their migration properties on TLC, with no regard for whether they are (20S)-protopanaxadiol, (20S)-protopanaxatriol- or oleanoic acid-derived. Ginsenoside Rf (not shown) is a major ginsenoside ofP. ginseng but is not found in P quinquefolius.

Ginsengoside Rbi (60) is a representative of the saponins derived from 20(5)-protopanaxadiol. It exhibits central nervous system-depressant and antipsychotic activity, protection against stress ulcer, increase of gastrointestinal motility and weak anti-inflammatory action. Rgi (61) -the major saponin of 20(5)-protopanaxatriol - shows weak CNS-stimulant action, antrfatigue activity and blood pressure activity [108,109] (O Scheme 25). 

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