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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

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ABSTRACT

Purpose

To investigate the ability of bacteria in the intestinal microbiome to convert naturally occurring primary ginsenosides in red ginseng extract to active secondary ginsenosides.

Methods

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.

Results

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.

Conclusion

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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Abbreviations

16s rRNA:

16s ribosomal RNA

C-K:

ginsenoside compound K

MTT:

3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide

Pa-b :

permeability from apical to basolateral side

UPLC:

ultra-performance liquid chromatography

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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.

Author information

Authors and Affiliations

  1. Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, Texas, 77030, USA

    Tao Niu, Zhen Yang, Song Gao, Taijun Yin & Ming Hu

  2. Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Diane L. Smith

  3. School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong

    Zhi-Hong Jiang

  4. Medical College of Wisconsin Cancer Center, 8701 West Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA

    Ming You

  5. Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030, USA

    Richard A. Gibbs

  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

    Joseph F. Petrosino

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  1. Tao Niu
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  2. Diane L. Smith
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  3. Zhen Yang
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  4. Song Gao
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  5. Taijun Yin
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  7. Ming You
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  8. Richard A. Gibbs
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  9. Joseph F. Petrosino
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  10. Ming Hu
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Corresponding authors

Correspondence to Joseph F. Petrosino or Ming Hu.

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Niu, T., Smith, D.L., Yang, Z. et al. Bioactivity and Bioavailability of Ginsenosides are Dependent on the Glycosidase Activities of the A/J Mouse Intestinal Microbiome Defined by Pyrosequencing. Pharm Res 30, 836–846 (2013). https://doi.org/10.1007/s11095-012-0925-z

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  • DOI: https://doi.org/10.1007/s11095-012-0925-z

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