Ginsenoside Rd enhances glutathione levels in H4IIE cells via NF-κB-dependent γ-glutamylcysteine ligase induction

Panax ginseng is widely used as herbal medicine in East Asia and the pharmacological effects of P. ginseng against certain chronic diseases might be explained by its antioxidative effects. Here, we show that ginsenoside Rd significantly increases both cellular glutathione (GSH) contents and the protein level of gamma-glutamylcysteine ligase (gamma-GCL) heavy chain in H4IIE cells (a rat hepatocyte cell line). Subcellular fractionation and Western blot analysis revealed that ginsenoside Rd increased the nuclear level of p65, but not of Nrf2. Moreover, ginsenoside Rd increased luciferase reporter gene activity in cells transfected with nuclear factor-kappa B (NF-kappa B) binding site-containing -1088 bp gamma-GCL promoter. However, ginsenoside Rd-inducible reporter activity was abolished when cells were transfected with NF-kappa B deletion mutant. These effects of ginsenoside Rd are suggested to underlie the putative anti-oxidative effect of Panax ginseng.