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.
Yuan
Hai-Dan
HD
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
Chung
Sung-Hyun
SH
D000818:Animals; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005285:Fermentation; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000032:analysis; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D028321:Plant Preparations / Q000737:chemistry / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013311:Streptozocin; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D016328:NF-kappa B; D028321:Plant Preparations; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases