Transcriptional activation of the Cu,Zn-superoxide dismutase gene through the AP2 site by ginsenoside Rb2 extracted from a medicinal plant, Panax ginseng.

We report here that the ginseng saponins induce the transcription of Cu,Zn-superoxide dismutase gene (SOD1), which is one of the major antioxidant enzymes. Total saponins and panaxatriol did not elevate the level of SOD1, but panaxadiol significantly increased SOD1. Among the panaxadiol fractions, ginsenoside Rb2 was a more specific and more remarkable inducer of the SOD1 gene than ginsenoside Rb1. Deletion analyses of the SOD1 promoter revealed that the proximal promoter is responsible for this induction. Mobility shift assays with cis-elements in the proximal promoter region showed that specific binding of the AP2 transcription factor was significantly increased by treatment with ginsenoside Rb2. Mutations of the AP2 binding sites in the heterologous promoter and natural context systems abolished the transcriptional activation by ginsenoside Rb2. These results suggest that the SOD1 gene was greatly activated by ginsenoside Rb2 through transcription factor AP2 binding sites and its induction.