Pharmacokinetics of Ginsenoside Deglycosylated by Intestinal Bacteria and Its Transformation to Biologically Active Fatty Acid Esters.

Abstract

Ginsenosides are deglycosylated by intestinal bacteria to active forms after oral administration. The present study demonstrated the pharmacodynamics of 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), an intestinal bacterial metabolite of ginsenosides, and the in vitro and in vivo antitumor activities of M1-metabolites in comparison with M1 using C57BL/6 mice and Wistar rats. M1 was selectively accumulated into the liver soon after its intravenous administration to mice, and mostly excreted as bile; however, some M1 was transformed to fatty acid ester (EM1) in the liver. EM1 was isolated from rats in a recovery dose of approximately 24 mol%. Structural analysis indicated that EM1 comprised a family of fatty acid mono-esters of M1. Because EM1 was not excreted as bile as M1 was, it was accumulated in the liver longer than M1. Although the cytotoxicity of M1 against B16-F10 melanoma cells was attenuated by fatty acid esterification, EM1 inhibited tumor growth more than M1 in vivo. These results suggest that the fatty acid M1 esters may be the real active principles of ginsenosides in the body.

Metabolism of Constituents in Huangqin-Tang, a Prescription in Traditional Chinese Medicine, by Human Intestinal Flora

“…Some papers reported that the metabolites of traditional Chinese materia medica, such as GA and PM-I, yield stronger pharmacological effect than the original compound, [27][28][29][30][31][32] and they were the ultimate active components in vivo. The metabolic mechanism of HIF is an important link for the pharmacological study of Chinese material medica.…”

Chemistry and Cancer Preventing Activities of Ginseng Saponins and Some Related Triterpenoid Compounds

“…Screening 31 species of human intestinal bacteria, all of which has the -glucosidase activity, was carried out, and Eubacterium sp. A-44 (17) and Provotella orise (18) appeared to be responsible for metabolizing ginsenoside Rb-1.…”

Isolation, Synthesis and Structures of Cytotoxic Ginsenoside Derivatives

“…Pharmaceutical studies have shown that orally ingested ginsenoside passes through the stomach and small intestine without decomposition, but the colonic bacteria cleave the oligosaccharide connected to the aglycone stepwise from the terminal sugar to afford the major metabolite, ginsenoside-M 1 [13][14]. Previous studies also showed that ginsenoside-M 1 was further esterified with fatty acids which could be sustained longer in the body; this result indicated that fatty acid ester of the M 1 might be the real anti-tumor active species in vivo [15].…”