Antibiotics attenuate anti-scratching behavioral effect of ginsenoside Re in mice

Ethnopharmacological relevance: The root of Panax ginseng CA Meyer (ginseng) has been used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine. Aim of the study: To understand the role of intestinal microflora in the pharmacological effect of ginsenoside Re, which is a main constituent of ginseng, we investigated its anti-scratching behavioral effect in the mice treated with or without antibiotics. Materials and methods: Ginsenoside Re was orally administered to the mice treated with antibiotics (cefadroxil, oxytetracycline and erythromycin mixture (COE), streptomycin or/and tetracycline) and then investigated the relationship between ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities of intestinal microflora and its antiscratching behavioral effect. The anti-scratching behavioral effects of ginsenosides were investigated in the increments of 1 h and 6 h after their oral administrations. The scratching behavioral frequency was measured for 1 h after treatment with histamine. Results: Ginsenoside Re inhibited histamine-induced scratching behavior in mice. The anti-scratching behavioral effect of ginsenoside Re was more potent 6 h after its oral administration than 1 h after. However, its inhibitory effect was significantly attenuated in mice treated with COE, but it nearly was not affected in mice treated with streptomycin and/or tetracycline. Treatment with COE also significantly lowered fecal ginsenoside Re-metabolizing β-glucosidase and α-rhamnosidase activities in mice, as well as fecal metabolic activity of ginsenoside Re to ginsenoside Rh1. The anti-scratching behavioral effect of ginsenoside Rh1, a metabolite of ginsenoside Re by intestinal microflora, 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. Conclusion: Ginsenoside Re may be metabolized to ginsenoside Rh1 by intestinal microflora, which enhances its anti-scratching behavioral effect by inhibiting NF-κB and c-jun activations. Crown