Protective effects of fermented ginseng on streptozotocin-induced pancreatic beta-cell damage through inhibition of NF-kappaB.

Ginseng (Panax ginseng C.A. Meyer) is widely used in Asian countries as a traditional medicine for the treatment of various diseases. It is known to have anti-inflammatory effects, although the mechanism is not clear. In this study, preventive effects of fermented ginseng (FG) against streptozotocin (STZ)-induced pancreatic beta-cell death was assessed in RINm5F insulinoma cells. FG markedly inhibited the production of nitrite in a dose-dependent manner. The decrease in nitrite production was found to correlate with reduced inducible nitric oxide (iNOS) protein and mRNA levels. To characterize the anti-inflammatory mechanism of FG at the transcriptional level, we examined effects of FG on the activity of nuclear factor-kappaB (NF-kappaB). FG reduced a translocation of the NF-kappaB subunit and NF-kappaB-dependent transcriptional activity. FG blocked signaling upstream of NF-kappaB activation, such as degradation of inhibitor factor-kappaBalpha (IkappaBalpha ) and phosphorylations of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK). These results suggest that FG protects against STZ-induced pancreatic beta-cell damage by downregulation of iNOS, cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha ) gene expressions by blocking NF-kappaB and mitogen-activated protein kinase activities.