Abstract

This study aims to investigate the effect of lactic acid bacteria (LAB) on in vitro and in vivo metabolism and the pharmacokinetics of ginsenosides in mice. When the in vitro fermentation test of RGE with LAB was carried out, protopanaxadiol (PPD) and protopanaxadiol (PPD), which are final metabolites of ginsenosides but not contained in RGE, were greatly increased. Compound K (CK), ginsenoside Rh1 (GRh1), and GRg3 also increased by about 30%. Other ginsenosides with a sugar number of more than 2 showed a gradual decrease by fermentation with LAB for 7 days, suggesting the involvement of LAB in the deglycosylation of ginsenosides. Incubation of single ginsenoside with LAB produced GRg3, CK, and PPD with the highest formation rate and GRd, GRh2, and GF with the lower rate among PPD-type ginsenosides. Among PPT-type ginsenosides, GRh1 and PPT had the highest formation rate. The amoxicillin pretreatment (20 mg/kg/day, twice a day for 3 days) resulted in a significant decrease in the fecal recovery of CK, PPD, and PPT through the blockade of deglycosylation of ginsenosides after single oral administrations of RGE (2 g/kg) in mice. The plasma concentrations of CK, PPD, and PPT were not detectable without change in GRb1, GRb2, and GRc in this group. LAB supplementation (1 billion CFU/2 g/kg/day for 1 week) after the amoxicillin treatment in mice restored the ginsenoside metabolism and the plasma concentrations of ginsenosides to the control level. In conclusion, the alterations in the gut microbiota environment could change the ginsenoside metabolism and plasma concentrations of ginsenosides. Therefore, the supplementation of LAB with oral administrations of RGE would help increase plasma concentrations of deglycosylated ginsenosides such as CK, PPD, and PPT.

Highlights

  • Red ginseng extract (RGE), one of the most popular herbal medicines, has been investigated for its efficacy

  • As most studies focused on the role of lactic acid bacteria (LAB) in in vitro ginsenoside metabolism, metabolism, we investigated the effects of LAB on in vivo ginsenoside metabolism and the we investigated the effects of LAB on in vivo ginsenoside metabolism and the resultant resultant pharmacokinetics of ginsenosides

  • To ensure the metabolic activity of LAB about ginsenosides, we conducted a fermentation test of RGE with LAB in vitro. Some ginsenoside metabolites, such as Compound K (CK), PPD, and PPT, which are not contained in natural RGE and final metabolites of ginsenosides, were significantly increased after incubating with LAB (Figure 3A,C)

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Summary

Introduction

Red ginseng extract (RGE), one of the most popular herbal medicines, has been investigated for its efficacy. Ginseng glycoside, called ginsenoside, is a major active pharmacological component, which causes the efficacy of RGE [2,3,4]. The serum concentrations of GRg1 and GRb1 showed a good correlation with NO releasing effect, a marker for anti-inflammatory effect [5,6]. The safety, pharmacokinetics, and preliminary efficacy of CK as an anti-rheumatoid arthritis drug are under clinical investigation in China (Study No. NCT03755258) [7]. The plasma exposure of CK showed a linear increase over the oral dose range of 100–400 mg of CK tablet. The plasma concentration of CK (Cmax 254.5 ng/mL) in subjects who received 3 g fermented RGE

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