3915

Background & Aims

Exposure of whole body to high dose of ionizing radiation induces acute gastrointestinal injury. Ginseng, the root of Panax ginseng C.A. Meyer, has been shown to have a protective effect on irradiated animals or cells. Ginsenosides are the most active components isolated from ginseng, and ginsenosides Rd and Re are identified as the effective compounds responsible for many pharmaceutical actions of ginseng. In the present study, we studied the molecular mechanisms of the radioprotective action of ginsenosides Rd and Re on the rat intestinal epithelial cells.

Materials & Methods

The rat intestinal IEC-6 cells were grown in DMEM medium supplemented with 5% (v/v) FCS. Cells were cultured in the presence of 5, 10, 20, 40 μM of Rd or Re with or without inhibitors of MEK (PD98059) or p38 MAPK (SB203580). Rd and Re were administered before and after various doses of(5, 10, 20 Gy)γ-irradiation and examined for apoptosis using the Hoechst staining, RT-PCR and Western blot analysis.

Results

We found that treatment with ginsenosides Rd and Re before and after γ-irradiation inhibited radiation-induced apoptosis in a dose-dependent manner (5, 10, 20, 40 μM) in IEC-6 cells. Rd or Re significantly decreased numbers of apoptotic cells in the presence of an inhibitor of MEK or p38 MAPK. Both Rd and Re blocked phosphorylation of ERK, p38 MAPK, and also decreased levels of cytochrome c, Bax, caspase 3, and caspase 9, but did not affect the Bcl-2 expression.

Conclusions

Ginsenosides Rd and Re protect and rescue rat intestinal epithelial cells from irradiation-induced apoptosis via inhibition of a mitochondria/caspase pathway and also through inhibition of MEK-ERK/p38 MAPK pathways.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA