Pharmacokinetic Profiling of Ginsenosides, Rb1, Rd, and Rg3, in Mice with Antibiotic-Induced Gut Microbiota Alterations: Implications for Variability in the Therapeutic Efficacy of Red Ginseng Extracts

Ginsenoside Rg3 is reported to contribute to the traditionally known diverse effects of red ginseng extracts. Significant individual variations in the therapeutic efficacy of red ginseng extracts have been reported. This study aimed to investigate the effect of amoxicillin on the pharmacokinetics of ginsenosides Rb1, Rd, and Rg3 in mice following the oral administration of red ginseng extracts. We examined the alpha-diversity and beta-diversity of gut microbiota and conducted pharmacokinetic studies to measure systemic exposure to ginsenoside Rg3. We also analyzed the microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1. Amoxicillin treatment reduced both the alpha-diversity and beta-diversity of the gut microbiota and decreased systemic exposure to ginsenoside Rg3 in mice. The area under the curve (AUC) values for Rg3 in control and amoxicillin-treated groups were 247.7 +/- 96.6 ng center dot h/mL and 139.2 +/- 32.9 ng center dot h/mL, respectively. The microbiome abundance and microbial metabolic activity involved in the biotransformation of ginsenoside Rb1 were also altered by amoxicillin treatment. The metabolizing activity was reduced from 0.13 to 0.05 pmol/min/mg on average. Our findings indicate that amoxicillin treatment potentially reduces the gut-microbiota-mediated metabolism of ginsenoside Rg3 in mice given red ginseng extracts, altering its pharmacokinetics. Gut microbiome variations may thus influence individual ginsenoside pharmacokinetics, impacting red ginseng extract's efficacy. Our results suggest that modulating the microbiome could enhance the efficacy of red ginseng.