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Alzheimer's disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ is generated by the regulated cleavage of a = 700 amino acid Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the Aβ domain to generate secreted sβAPPα or at the N-terminal and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. The aim of this study was to elucidate the antioxidant neuroprotective mechanism of Bombusae concretioSalicea (BC). BC was effective protectants against oxidative glutamate toxicity in the murine neuroblastoma cells (N2a) and human neuroblastoma cells (SK-N-MC). BC exhibited similar protective properties against oxidative glutamate toxicity and H2O2toxicity. BC exhibited an antioxidant activity at approximately 20 μg/ml. BC of 5 μg/ml was ineffective in preventing the oxidative modification of LDL. The half-maximal effective concentration for BC was 16 μg/ml. These results suggested that BC supplementation in elderly men may be protective in the treatment of Alzheimer's disease (AD). We report here that treatment with BC increases the secretion of the nonamyloidogenic APP fragment, sβAPPα and decreases the secretion of Aβ peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that BC supplementation in elderly men may be protective in the treatment of AD.

Bombycis corpus(BC) or Bombyx Batryticatus, a batryticatedsilkworm and white-stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In the present study, we have examined the protective effect of the water extracts against Amyloid- β(A β) 25–35 peptide-induced cytotoxicity by microscopic observation and LDH assay, and its action on antioxidative enzymes using cultured astrocyte cells. A β25–35-induced cell death was protected by the application of water extract of BC in a dose-dependent manner, and concentrations of 10−6to 10−7g ml−1showed a significant effect compared to exposure of A β25–35 alone. When antioxidative enzyme activities such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione-S transferase (GST) were assayed after A β25–35 treatment, most enzyme activities were decreased in a similar fashion. BC treatment of A β25–35-treated astrocytes did not affect the enzyme activities of catalase, GSH-Px and GST. However, only SOD activity was enhanced by BC treatment and this may result from the potentiation of the antioxidative ability of BC. The protective effect of BC against cytotoxicity induced by Aβ25–35 strongly indicates that BC could be a protective agent for free radical generating compounds, and that A β25–35 is not only a potent lipid peroxide inducer, but can also cause changes in antioxidative enzymes. From the results, it was concluded that BC has a protective effect against A β-induced cytotoxicity in cultured astrocyte cells through the inhibition of lipid peroxidation and protection of antioxidative enzymes.