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

The root of Panax ginseng CA Meyer (ginseng) has been used for diabetes, cancer, stress and allergic diseases in the traditional Chinese medicine. 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. 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. 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. 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.