Ilex latifolia Prevents Amyloid β Protein (25–35)-Induced Memory Impairment by Inhibiting Apoptosis and Tau Phosphorylation in Mice

摘要

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 Ca²⁺ 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.