Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity.
We have previously reported that acteoside isolated from the leaves of Callicarpa dichotoma has significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultured rat cortical cells. To determine the essential structural moiety within this phenylethanoid glycoside needed to exert neuroprotective activity, acteoside was hydrolyzed with acid into its aglycones, caffeic acid and 3',4'-dihydroxylphenylethanol. Caffeic acid and 3',4'-dihydroxylphenylethanol also showed significant neuroprotective activities. Acteoside and its aglycones inhibited glutamate-induced intracellular Ca2+ influx resulting in overproduction of nitric oxide and reduced the formation of reactive oxygen species. These compounds preserved the mitochondrial membrane potential and the activities of antioxidative enzymes, such as superoxide dismutase, glutathione reductase and glutathione peroxidase reduced by glutamate. It was followed by the preservation of the level of glutathione and finally the inhibition of membrane lipid peroxidation.
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Kwanak-Gu, Seoul 151-742, South Korea.
Kyung Ah
KA
Koo
Seung Hyun
SH
Kim
Tae Hwan
TH
Oh
Young Choong
YC
Kim
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D059808:Polyphenols
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002109:Caffeic Acids; D002118:Calcium; D003373:Coumaric Acids; D018691:Excitatory Amino Acid Antagonists; D005960:Glucosides; D005978:Glutathione; D008054:Lipid Peroxides; D008563:Membrane Lipids; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009569:Nitric Oxide; D010636:Phenols; D010714:Phosphatidylethanolamines; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C058956:acteoside; D059808:Polyphenols; C040048:caffeic acid