Pharmaceutical Research

, Volume 30, Issue 3, pp 836–846 | Cite as

Bioactivity and Bioavailability of Ginsenosides are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing

  • Tao Niu
  • Diane L. Smith
  • Zhen Yang
  • Song Gao
  • Taijun Yin
  • Zhi-Hong Jiang
  • Ming You
  • Richard A. Gibbs
  • Joseph F. PetrosinoEmail author
  • Ming HuEmail author
Research Paper



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.


16S 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.

Supplementary material

11095_2012_925_MOESM1_ESM.docx (1.6 mb)
ESM 1 (DOCX 1669 kb)


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Tao Niu
    • 1
  • Diane L. Smith
    • 2
  • Zhen Yang
    • 1
  • Song Gao
    • 1
  • Taijun Yin
    • 1
  • Zhi-Hong Jiang
    • 3
  • Ming You
    • 4
  • Richard A. Gibbs
    • 5
  • Joseph F. Petrosino
    • 6
    Email author
  • Ming Hu
    • 1
    Email author
  1. 1.Department of Pharmacological and Pharmaceutical SciencesCollege of Pharmacy, University of HoustonHoustonUSA
  2. 2.Program in Translational Biology and Molecular MedicineBaylor College of Medicine, One Baylor PlazaHoustonUSA
  3. 3.School of Chinese MedicineHong Kong Baptist UniversityKowloon TongHong Kong
  4. 4.Medical College of Wisconsin Cancer CenterMilwaukeeUSA
  5. 5.Human Genome Sequencing Center, Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  6. 6.Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and MicrobiologyHuman Genome Sequencing Center, Baylor College of MedicineHoustonUSA

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