Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia.
Mongolian gerbils subjected to transient global ischemia exhibit neuroprotection against ischemic neuronal cell death in the hippocampal CA1 region when treated with vanillin, 4-hydroxybenzyl aldehyde (4-HBAL) and 4-hydroxybenzyl alcohol (4-HBA), which are active components of Gastrodia elata Blume. Pre- and post-insult vanillin, 4-HBAL and 4-HBA treated-animals showed a significant increase in neuronal survival (66.32%, 43.21% and 64.58%, respectively) compared to vehicle-treated animals. Animals exhibited a gender difference in this neuroprotective effect. To study the neuroprotective mechanism of 4-HBA, we investigated N-methyl-d-aspartate (NMDA) receptor 1 (NR1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and gamma-aminobutyric acid transaminase (GABA-T) immunoreactivity at various times after ischemic insults. Treatment with 4-HBA did not affect NR1 expression levels, down-regulated 8-OHdG immunoreactivity, and increased GABA-T expression levels after global ischemia, suggesting that 4-HBA inhibited NR1 stimulation. Moreover, GABA-T was rapidly increased in the early stage after ischemia, which might enhance the survival of cells by supplying energy to the CA1 region. These results suggest that 4-HBA inhibits oxidative stress and excitotoxicity for at least 12 h and suppresses neuronal death in CA1 region. Diethyl ether fractions of GE scavenged hydroxyl radical (OH.) and showed antioxidant activity on lipid peroxidation. Vanillin and 4-HBA treatment blocked oxidative damage in PC12 cells. The neuroprotective effect has therapeutic significance and these compounds need to be evaluated for potential use in protecting against neuronal cell damage during stroke.
Kim
Hyeon Ju
HJ
Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul 110-799, South Korea. Kimhyunju@mail.nih.gov
Hwang
In Koo
IK
Won
Moo Ho
MH
D000818:Animals; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D001592:Benzyl Alcohols / Q000737:chemistry / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D005260:Female; D031668:Gastrodia / Q000737:chemistry; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D008517:Phytotherapy
D001547:Benzaldehydes; D001592:Benzyl Alcohols; D018696:Neuroprotective Agents; C018966:4-hydroxybenzyl alcohol; C100058:vanillin; C011483:4-hydroxybenzaldehyde