Bioactivity and Bioavailability of Ginsenosides are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing
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To investigate the ability of bacteria in the intestinal microbiome to convert naturally occurring primary ginsenosides in red ginseng extract to active secondary ginsenosides.
Anti-proliferative ginsenoside activity was tested using mouse lung cancer LM1 cells. Permeabilities were evaluated in Caco-2 cell monolayers. Systemic exposure of secondary ginsenosides was determined in A/J mice. 16S rRNA gene pyrosequencing was used to determine membership and abundance of bacteria in intestinal microbiome.
Secondary ginsenoside C-K exhibited higher anti-proliferative activity and permeability than primary ginsenosides. Significant amounts of secondary ginsenosides (F2 and C-K) were found in blood of A/J mice following oral administration of primary ginsenoside Rb1. Because mammalian cells did not hydrolyze ginsenoside, we determined the ability of bacteria to hydrolyze ginsenosides and found that Rb1 underwent stepwise hydrolysis to Rd, F2, and then C-K. Formation of F2 from Rd was the rate-limiting step in the biotransformation of Rb1 to C-K.
Conversion to F2 is the rate-limiting step in bioactivation of primary ginsenosides by A/J mouse intestinal microbiome, whose characterization reveals the presence of certain bacterial families capable of enabling the formation of F2 and C-K in vivo.
KEY WORDS16S rRNA gene sequencing F2 and C-K ginseng ginsenosides Rb1 microbiome permeability pharmacokinetic profile rate-limiting step Rd stepwise metabolism
- 16s rRNA
16s ribosomal RNA
ginsenoside compound K
3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
permeability from apical to basolateral side
ultra-performance liquid chromatography
Acknowledgments and disclosures
This work was supported by a grant from the National Institutes of Health [AT-005522] to Ming Hu at University of Houston, Ming You at Medical College of Wisconsin and Zhi-hong Jiang at Hong Kong Baptist University.
Niu and Smith contributed equally to this paper.
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