Neuroprotection and enhancement of spatial memory by herbal mixture HT008-1 in rat global brain ischemia model.
To investigate whether HT008-1, a prescription used in traditional Korean medicine to treat mental and physical weakness, has a neuroprotective effect on a rat model of global brain ischemia and an enhancing effect against memory deficit following ischemia. Global brain ischemia was induced for 10 min by using 4-vessel occlusion (4-VO). HT008-1 was orally administered at doses of 30, 100, and 300 mg/kg respectively twice at 0 and 90 min after ischemia. The effect on memory deficit was investigated by using a Y-maze neurobehavioral test 4 days after brain ischemia, and the effect on neuronal damage was measured 7 days after ischemia. The mechanism of action was studied immunohistochemically using an anti-CD11b (OX-42) antibody. The oral administration of HT008-1 at 100 and 300 mg/kg significantly reduced hippocampal neuronal cell death by 49% and 53%, respectively, compared with a vehicle-treated group, and also improved spatial memory function in the Y-maze test. Immunohistochemically, HT008-1 inhibited OX-42 expression in the hippocampus. The effects of HT008-1 were more pronounced than those of its individual herb components. The herbal mixture HT008-1 protects the most vulnerable CA1 pyramidal cells of the hippocampus and enhances spatial memory function against global brain ischemia; an anti-inflammatory effect may be one of the mechanisms of action.
Kim
Yun Tai
YT
Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.
Yi
Youn-Ju
YJ
Kim
Mi-Yeon
MY
Bu
Youngmin
Y
Jin
Zhen Hua
ZH
Choi
Hoyoung
H
Doré
Sylvain
S
Kim
Hocheol
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D009474:Neurons / Q000473:pathology; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D004365:Drugs, Chinese Herbal; D004281:Docosahexaenoic Acids