Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2003

After switching cultured cerebellar granule neurons from a serum-supplemented medium containing 25 mM K[superscript +] (high K[superscript +]) to a serum-free medium containing 5 mM low K[superscript +] (low K[superscript +]) for 24 hr, approximately 50% of neurons had loss their viability. In addition, cellular lipid peroxidation levels increased to approximately 130% and total glutathione content decreased to approximately 65% of control cultures. Coexposure of cerebellar granule neurons with asiaticoside (1-100 micrometre) and low potassium (5 mM) medium for 24 hr had no effect on low K[superscript +]-induced cell death. Preexposure of cerebellar granule neurons with asiaticoside (1-100 micromolar) for 24 hr and then shifting to low potassium medium for 24 hr revealed a significant neuroprotective effect only at 1 micromolar of asiaticoside while similar preexposure with asiaticoside for 48 hr failed to protect cultured neurons from low K[superscript +]-induced cell death at all concentrations used. Preexposure of cultured neurons with 1 micromolar asiaticoside for 24 hr in high K[superscript +] medium did not decrease basal cellular lipid peroxidation levels but effectively prevented low K[superscript +]-induced increase in lipid peroxidation. Moreover, this preexposure had no effect on basal total glutathione content and displayed a marginal preventive effect on low K[superscript +]-induced decrease in total glutathione content. In conclusion, asiaticoside by itself displayed both neuroprotective and neurotoxic effects on cultured cerebellar granule neurons, depending on the concentration and duration of exposure. Neuroprotective effect against low K[superscript +]-induced cell death is clearly evident only under specific conditions of exposure, namely, preexposure to 1 micromolar asiaticoside for 24 hr. This particular preexposure can prevent low potassium medium induced cell death in cultured rat cerebellar granule neurons, in conjunction with increasing mitochondrial function, decreasing cellular lipid peroxidation, and marginal restoring of glutathione diminution. However, the mechanism of action underlying biphasic effects of asiaticoside on cultured neurons is still unclear at the present time