Ursolic acid is the major component of extracts of the Chinese herb, Souyang. This study determines whether and how ursolic acid protects against kainate-induced excitotoxicity in rat hippocampus. Primary neuronal cultures of cells isolated from the hippocampi of 7-day-old rats were treated with 150 microM kainate. After 2 h of treatment, free radicals were elevated and mitochondrial membrane potential was reduced significantly, and after 12 h, cell viability was decreased. Pretreatment with 5-15 microM ursolic acid dose-dependently and significantly attenuated the kainate-induced damage as well as alleviating the decrease in mitochondrial membrane potential and suppressing the increase in free radical generation. The results suggest that multiple mechanisms including modulation of AMPA receptor, protection of mitochondria, decrease in free radical generation, and scavenging of free radicals might be involved in ursolic acid protection against kainate-induced cell toxicity.
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