Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in rats.
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.
Shih
Yang-Hsin
YH
School of Medicine, Taipei Medical University, Taiwan.
Chein
Yi-Chun
YC
Wang
Jia-Yi
JY
Fu
Yu-Show
YS
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D007608:Kainic Acid; D018696:Neuroprotective Agents; D010793:Phthalazines; D014315:Triterpenes; D000097245:Ursolic Acid; C487116:4-aminophenyl-1,2-dihydro-1-methyl-2-propylcarbamoyl-6,7-methylenedioxyphthalazine