Metabolism of Ginsenoside Re Isolated from Ginseng by Intestinal Microflora and its Biological Activities

Most herbal medicines, including ginseng, are orally administered to human. Therefore, their components inevitably contact the intestinal microflora in the gastrointestinal tract and may be metabolized by intestinal microflora, before absorption from the gastrointestinal tract to the blood. Therefore, we investigated the metabolites of ginsenoside Re from the root of Panax ginseng CA Meyer (ginseng), which is used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine. The bioactive metabolite transforming lactic acid bacteria (LAB) from the intestinal microflora was then screened. Ginsenoside Re was mainly metabolized ginsenosides Rh1 and F1 via ginsenosodie Rg1, with protopanaxatriol as a minor metabolite. All isolated as ginsenoside Re metabolizing intestinal bacteria produced ginsenoside Rh1 or F1. Of these bacteria, α-Rhamnosidase and β-glucosidase from Bacterioides JY-6 were able to hydrolyze ginsneoside Re and ginsenoside Rg1, respectively. However, they did hydrolyzed ginsenoside Rh1 or F1. Of LAB isolated from human intestines, Bifidobacterium K-525 most effectively produced ginsenoside Rh1. When ginsenoside Re, in the absence or presence of antibiotics, was orally administered to mice, ginsenoside Re inhibited histamine-induced scratching behavior in mice untreated with antibiotics, but significantly attenuated its inhibition in mice treated with antibotics, although it was reduced barely in mice treated with streptomycin and/or tetracycline. Treatment with antibiotics significantly reduced fecal ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities in mice. Furthermore, the metabolic activity of ginsenoside Re to ginsenoside Rh1 by the fecal suspension of mice treated with antibiotics was significantly lower than that of mice untreated with antibiotics. The anti-scratching behavioral effect of ginsenoside Rh1 was superior to that of ginsenoside Re. Ginsenoside Rh1 potently inhibited the expression of IL-4 and TNF-α, as well as the activation of NF-κB and c-jun activation in histamine-stimulated scratching behavioral mice. Furthermore, ginsenoside Rh1 more potently inhibited the activation of NF-κB in lipopolysaccharide-induced peritoneal macrophages than ginsenoside Re. Based on these findings, ginsenoside Re may be metabolized to ginsneoside Rh1 by intestinal microflora, which enhance its anti-allergic effect by inhibiting NF-κB and c-jun activation.