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.
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- Bioactivity and Bioavailability of Ginsenosides are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing
Volume 30, Issue 3 , pp 836-846
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- Additional Links
- 16S rRNA gene sequencing
- F2 and C-K
- ginsenosides Rb1
- pharmacokinetic profile
- rate-limiting step
- stepwise metabolism
- Industry Sectors
- Author Affiliations
- 1. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, Texas, 77030, USA
- 2. Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
- 3. School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong
- 4. Medical College of Wisconsin Cancer Center, 8701 West Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA
- 5. Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA
- 6. Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and Microbiology, Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA