Effects of broad-spectrum antibiotics on the metabolism and pharmacokinetics of ginsenoside Rb1: a study on rats׳ gut microflora influenced by lincomycin

Abstract

Ginsenoside Rb1 is a biologically active compound that is abundant in ginseng (Panax ginseng). It has been reported that ginsenosides could be metabolized by enzymes and bacteria in the large intestine. In this study, the effects of intestinal bacteria on the metabolism and pharmacokinetics of ginsenoside Rb1 were investigated using lincomycin-treated rat models (4.8g/kg and 0.12g/kg). Specifically, ginsenoside Rb1 was incubated anaerobically with rat fecal suspensions obtained from the control and two model groups at 0, 6, 12, 24, and 48h. Ginsenoside Rb1 and its metabolites were determined by HPLC analysis. Compared with the normal rats case where Rd and compound K were detected in the incubation mixture, ginsenoside Rd and F2 were found in the 0.12g/kg group, but only Rd was found in the 4.8g/kg group. Moreover, fecal β-glucosidase activity was significantly lower in lincomycin-treated (0.12g/kg and 4.8g/kg) model rats. After administration of Rb1 to rats, ginsenoside Rb1 and its metabolites Rd, Rg3, and Rh2 were detectable in normal rat urine, whereas none was detected in the two model groups. The plasma concentration-time Rb1 were compared between model groups and normal rats. The systemic exposure as evidenced by the AUC and T1/2 values was significantly higher in model groups than in normal rats. Our findings demonstrated that consumption of lincomycin could lead to the formation of specific metabolites and pharmacokinetic changes of ginsenoside Rb1 in the gut, attributed to alterations in metabolic activities of intestinal bacteria. Our results also suggested that patients who want to use intestinal bacteria-metabolized drugs such as ginseng (Panax ginseng) should pay attention to the profile of intestinal bacteria or potential drug interactions to ensure therapeutic efficacy.

Keywords: Compound K (PubChem CID: 9852086); Gastrointestinal tract; Ginsenoside F2 (PubChem CID: 9918692); Ginsenoside Rb1; Ginsenoside Rb1 (PubChem CID: 432524); Ginsenoside Rd (PubChem CID: 12855925); Ginsenoside Rg3 (PubChem CID: 53447399); Ginsenoside Rh2 (PubChem CID: 14081290); Lincomycin; Metabolism; Pharmacokinetics.