ABSTRACT
The present study aims to investigate the effect of methanol extract of Korean mistletoe (KM; Viscum album var. coloratum), on amyloid beta protein (Abeta) (25-35), a synthetic 25-35 amyloid peptide, -induced neurotoxicity in cultured rat cerebral cortical neurons and memory impairment in mice. Exposure of cultured neurons to 10 microM Abeta (25-35) for 24 h induced a neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM (10, 30 and 50 microg/ml) significantly inhibited the Abeta (25-35)-induced apoptotic neuronal death. KM (50 microg/ml) inhibited 10 microM Abeta (25-35)-induced elevation of intracellular calcium concentration ([Ca2+]i), which was measured by a fluorescent dye, Fluo-4 AM. Glutamate release into medium and generation of reactive oxygen species (ROS) induced by 10 microM Abeta (25-35) were also inhibited by KM (10, 30 and 50 microg/ml). These results suggest that KM may mitigate the Abeta (25-35)-induced neurotoxicity by interfering with the increase of [Ca2+]i and then inhibiting glutamate release and generation of ROS in cultured neurons. In addition, orally administered KM (25 and 50 mg/kg, 7 days) significantly prevented memory impairment induced by intracerebroventricular injection of Abeta (25-35) (8 nmol). Taken together, it is suggested that anti-dementia effect of KM is due to its neuroprotective effect against Abeta (25-35)-induced neurotoxicity and that KM may have therapeutic role in prevention of the progression of Alzheimer's disease.