Bioactivity and bioavailability of ginsenosides are dependent on the glycosidase activities of the A/J mouse intestinal microbiome defined by pyrosequencing.

TitleBioactivity and bioavailability of ginsenosides are dependent on the glycosidase activities of the A/J mouse intestinal microbiome defined by pyrosequencing.
Publication TypeJournal Article
Year of Publication2013
AuthorsNiu, T, Smith, DL, Yang, Z, Gao, S, Yin, T, Jiang, Z-H, You, M, Gibbs, RA, Petrosino, JF, Hu, M
JournalPharm Res
Volume30
Issue3
Pagination836-46
Date Published2013 Mar
ISSN1573-904X
KeywordsAnimals, Antineoplastic Agents, Phytogenic, Bacteria, Biological Availability, Biotransformation, Caco-2 Cells, Cell Line, Tumor, Cell Proliferation, Drugs, Chinese Herbal, Ginsenosides, Glycoside Hydrolases, Humans, Hydrolysis, Intestines, Male, Metagenome, Mice, Neoplasms, Panax, RNA, Bacterial
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.

DOI10.1007/s11095-012-0925-z
Alternate JournalPharm. Res.
PubMed ID23254888
PubMed Central IDPMC4372807
Grant ListAT-005522 / AT / NCCIH NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States