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Ginsenoside-Rg₁ (G-Rg₁) from the roots of Panax ginseng C. A. Meyer has been shown to bind to the glucocorticoid receptor (GR). To further explore the effect of G-Rg₁ binding to GR, a luciferase reporter gene containing two copies of a glucocorticoid response element was constructed and transiently transfected into FTO2B rat hepatoma cells. A dose-dependent induction of the reporter gene was observed in response to G-Rg₁, and the inductive effect was blocked by treatment with the antiglucocorticoid RU486. In addition, both G-Rg₁- and dexamethasone (Dex)-induced transcription was synergistically enhanced by the treatment of dibutyryl cAMP (Bt₂-cAMP). G-Rg₁ treatment also led to the down-regulation of intracellular GR content, which was similar to the effect of Dex. By showing that G-Rg₁ down-regulates GR and induces GR-mediated transcription synergistically with cAMP, we conclude that G-Rg₁ is a …