title: Bioactivity and bioavailability of ginsenosides are dependent on the glycosidase activities of the A/J mouse intestinal microbiome defined by pyrosequencing.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 1441 Moursund Street, Houston, Texas, 77030, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Niu
authors.forename: Diane L
authors.initials: DL
authors.lastname: Smith
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Taijun
authors.initials: T
authors.lastname: Yin
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: You
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001419:Bacteria / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D001682:Biological Availability; D001711:Biotransformation; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D036145:Ginsenosides / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D005894:Panax / Q000737:chemistry; D012329:RNA, Bacterial / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D012329:RNA, Bacterial; D006026:Glycoside Hydrolases