Protection of Neurons against Amyloid β Protein (25–35)-induced toxicity by Korean mistletoe

Semi-parasitic plants, mistletoes (Loranthaceae), have been traditionally used as a sedative, analgesic, anti-spasmodic, cardiotonic and anticancer agent. Amyloid β protein (Aβ) (25–35) is believed to play a central role in the pathophysiology of Alzheimer's disease (AD) [1]. In the present study, the protective effect of a methanol extract from whole plant of Korean mistletoe (KM; Viscum album L. var. coloratum Owhi containing ca 0.01% (w/w) of triterpenes) against Aβ (25–35)-induced neurotoxicity was examined in primary cultured rat cortical neurons. KM (10 to 50µg/ml) prevented the Aβ (25–35) (10µM)-induced neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM significantly inhibited Aβ (25–35)-induced elevation of the cytosolic Ca²⁺ concentration which was measured by a fluorescent dye, fluo-4 AM. KM also inhibited generation of reactive oxygen species induced by Aβ (25–35). The protective effect of KM against Aβ (25–35)-induced memory impairment in mice was examined using passive avoidance test [2]. Memory impairment model in mice was established via intracerebroventricular (i.c.v.) microinjection of Aβ (25–35) (8 nmol). Aβ (25–35)-induced memory impairment was markedly improved by chronic administration of KM (25 and 50mg/kg, PO, 8 days). Data were expressed as mean±SEM and statistical significance was assessed by one-way analysis of variance (ANOVA) with subsequent Tukey's tests. In conclusion, the protection against Aβ (25–35)-induced neurotoxicity in in vitro and in vivo by KM may explain its inhibitory action on the progression of AD, and provide the pharmacological basis of its clinical usage in treatment of neurodegeneration in AD.

Acknowledgements: This work was supported by a grant from BioGreen 21 Program, Rural Development Administration, Republic of Korea.

References: [1] Hsiao K. K., et al., (1995). Neuron, 15, 1203–1218 [2] Schwarzberg, H., et al., (1989). Neuropeptides, 13, 79–81