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

Abstract

Purpose The ability of bacteria in the intestinal microbiome to convert naturally occurring primary ginsenosides in red ginseng extract or RGE to active secondary ginsenosides was investigated. Methods The anti-proliferative activity of ginsenosides was tested using the mouse lung cancer LM1 cells. Their 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 the intestinal microbiome. Results Secondary ginsenoside C-K exhibited higher anti-proliferative activity and permeability than primary ginsenosides, and significant amounts of secondary ginsenosides (F2 and C-K) were found in the blood of A/J mice following oral administration of the primary ginsenoside Rb1. Because mammalian cells did not hydrolyze ginsenoside, we determined the ability of bacteria to hydrolyze ginsenosides and found that the primary ginsenoside 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 This is the first study to characterize the A/J mouse intestinal microbiome and reveal the presence of certain bacterial families capable of efficiently converting inactive primary ginsenosides to active secondary ginsenosides in vivo.

Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice

“…In our study, to investigate whether the two signaling pathways interacted with one another and how they interacted in lung cancer, we induced lung cancer with urethane in ovariectomized mice and stimulated these mice with estrogen or IGF‐1 alone or in combination. The Kunming mice used in our study have a lower spontaneous tumor rate than A/J mice, are stable strains and have been used for successful urethane‐induced lung adenocarcinoma (LADE) in many experiments . Investigation of the expression of the above key signaling molecules and their correlation by tissue microarray‐immunohistochemistry (TMA‐IHC), Western blot and real‐time fluorescence‐quantitative polymerase chain reaction (FQ‐PCR) provides an important basis for studying whether the ER and IGF‐1R signaling pathways synergistically promote lung cancer development and helps to identify targets for combined targeted therapy for lung cancer.…”

Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract

“…Fecal lysate was prepared by the method described previously with some modifications. [ 20 ] Briefly, Flesh feces of ten rats were collected, and about 1 g were immediately mixed with 9 mL ice-cold 0.1 mM phosphate buffer solution (PBS), (pH 7.4) and vortexed for 5 s followed by centrifugation at 1,000 rpm and 4°C for 15 min. The pellet was resuspended in 10 mL ice cold PBS, then sonicated in ice water bath for 45 min, and finally centrifuged at 15,000 rpm and 4°C for 30 min.…”

Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio-platycodin D in Jiegeng

“…The fecal lysate was prepared using previously described methods with some modifications (Niu et al, 2013).…”