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Protective Effect of Ginsenoside Rgl on H2O2-Induced Cell Death by the Decreased Ceramide Level in LLC-PK1 Cells

  • Published : 2006.03.01

Abstract

Ceramide has been involved in celt death and acted as a lipid mediator of stress responses. Elevation of ceramide level was reported to occur in oxidative stress and lead to cell death in many cell types. This study was undertaken to elucidate a protective role of ginsenoside Rgl in cell death induced by oxidative stress. When LLC-PK1 cells were treated with $H_2O_2$ at a concentration of $400{\mu}M$ for 5 hr, cell death was observed and a released LDH activity indicative of cytotoxicity was Increased. $H_2O_2$ exposure to LLC-PK1 cells was shown to elevate the content of total ceramide by approximately 200% compared to control cells. Ceramide level was hypothesized to be a key to a reversal of cell death to survival. Ginsenoside Rgl at the concentrations ranging from 12.5 to $250{\mu}M$ protected LLC-PK1 cells from cell death induced by $H_2O_2\;at\;400{\mu}M$ for 5 hr, and decreased the ceramide level relative to $H_2O_2$. Ginsenoside Rgl inhibited neutral human ceramidase by 71% of controls, while sphingomyelinase was not inhibited. These results suggest that ginsenoside Rgl show the protection against cell death via the modulation of ceramide metabolism, and ceramide may be a promising therapeutic target for human diseases related to cell death.

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