Ginseng (the roots of Panax ginseng C. A. MEYER, Alariaceae) has been used as one of the most valuable traditional medicines in the Orient for over 2000 years. It contains a number of active constituents including saponins, essential oil, phytosterol, carbohydrates and sugars, organic acids, nitrogenous substances, amino acids and peptides, plus vitamins and minerals. 2,3) Pharmacological and clinical studies conducted over the past 40 years have focused on radioprotective, antitumor, antiviral and metabolic effects; antioxidant activities; nervous system and reproductive performance; effects on cholesterol and lipid metabolism, and endocrinological activity. 4,5) More recently, epidemiological studies have identified an association between ginseng intake and a decreased incidence and growth of cancers. [6][7][8][9] The main ingredients of ginseng are ginsenosides, glycosides containing an aglycone (protopanaxadiol or protopanaxatriol) with a dammarane skeleton. Numerous researchers have contributed to the accumulation of evidence that ginsenosides are responsible for the pharmacological effects of ginseng; however, some have obtained results from direct addition of ginsenoside into cell cultures in vitro or from intraperitoneal (i.p.) or intravenous (i.v.) injection to experimental animals, though ginseng is generally taken orally.Pharmacokinetic studies have demonstrated that orally administered ginsenosides pass through the stomach and small intestine without decomposition by either gastric juice or liver enzymes into the large intestine, where ginsenosides are metabolized by colonic bacteria. Protopanaxadiol monoglucoside (M1) and protopanaxatriol (M4) are major bacterial metabolites of ginsenosides, 10) and we have shown that these metabolites mediate the anticancer actions of ginsenosides. 11,12) We recently have found that M1 is further biotransformed to its fatty acid-conjugates, 13) which potentiate the activity of M1 through effective accumulation in the body.14) This allows us to hypothesize that M4 is also esterified with fatty acids, though Kasai et al. have reported that M4 is biotransformed to its 20,24-epoxide (protopanaxatriol oxide II, PO) by liver microsomes in vitro.15) Thus, we investigated the real active principle of M4 in the body, using C57BL/6 mice bearing B16-BL6 melanoma.
MATERIALS AND METHODSInstruments Mass spectra were obtained on a JEOL JMS-700T spectrometer by the FAB method. NMR spectra were recorded on a JEOL JNM-LA400 spectrometer [solvent, dimethyl Animals and Housing C57BL/6 mice, colonized with the intestinal anaerobes Bacteroides/Prevotella and Lactobacillus to an extent similar to that seen in humans, 18) were maintained and inbred in the Animal Experimental Laboratory, Itto Institute of Life Science Research in accordance with the institute's animal care guidelines. The animals were housed in plastic cages with wire tops and sawdust bedding with a 12-h light-dark cycle under conventional conditions. The animals were fed a low-fat diet for long-term breeding Medicine, ...