Ilex latifolia Prevents Amyloid β Protein (25-35)-Induced Memory Impairment by Inhibiting Apoptosis and Tau Phosphorylation in Mice.
Ilex latifolia Thunb. (Aquifoliaceae), a Chinese bitter tea called "kudingcha," has been widely consumed as a health beverage and found to possess antioxidant, antidiabetic, antihypertensive, anti-inflammatory, and anti-ischemic activities. The aim of the present study was to investigate the neuroprotective effects of an ethanol extract of I. latifolia against amyloid β protein (Aβ)-induced memory impairment in mice and neurotoxicity in cultured rat cortical neurons. Memory impairment in mice was induced by intracerebroventricular injection of 15 nmol Aβ (25-35) and measured by the passive avoidance test and Morris water maze test. Chronic administration of I. latifolia (25-100 mg/kg, p.o.) significantly prevented Aβ (25-35)-induced memory loss. I. latifolia also prevented the decrease of glutathione concentrations, increased lipid peroxidation, expression of phosphorylated tau (p-tau), and changes in apoptosis-associated proteins in the memory-impaired mouse brain. Exposure of cultured cortical neurons to 10 μM Aβ (25-35) for 36 h induced neuronal apoptotic death. The neuronal cell death, elevation of intracellular Ca(2+) concentration, generation of reactive oxygen species, and expression of proapoptotic proteins caused by Aβ (25-35) in the cultured neurons were inhibited by treatment with I. latifolia (1-50 μg/mL). These results suggest that I. latifolia may have a possible therapeutic role in managing cognitive impairment associated with Alzheimer's disease. The underlying mechanism might involve the antiapoptotic effects mediated by antioxidant activity and inhibition of p-tau formation.
1 College of Veterinary Medicine, Chungbuk National University , Cheongju, Korea.
Joo Youn
JY
Kim
1 College of Veterinary Medicine, Chungbuk National University , Cheongju, Korea.
Hong Kyu
HK
Lee
1 College of Veterinary Medicine, Chungbuk National University , Cheongju, Korea.
Ji Yeon
JY
Jang
2 Han Kook Shin Yak , Chungnam 320-854, Korea.
Jae Kuk
JK
Yoo
1 College of Veterinary Medicine, Chungbuk National University , Cheongju, Korea.
Yeon Hee
YH
Seong
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D030017:Ilex; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016875:tau Proteins; D005978:Glutathione; D002118:Calcium
Alzheimer's disease; Ca2+ signaling; antioxidant; cognition; neuroprotection