Identification of an antiamyloidogenic substance from mulberry leaves.

Fibrillar aggregates of amyloid beta-peptides are major constituents of the plaques found in the brains of patients with Alzheimer's disease, and have been implicated in the neurotoxicity of Alzheimer's. We previously reported that the methanol extract of mulberry leaves inhibits the formation of amyloid beta-peptide (1-42)-fibrils in vitro, and protects hippocampal neurons from amyloid beta-peptide (1-42)-induced cell death. In this study, we identified antiamyloidogenic substances, pheophorbide a, kaempferol -3-O-glucoside, and kaempferol -3-O-(6-malonyl) glucoside, from the methanol extract of mulberry leaves. We also compared the antiamyloidogenic activity of pheophorbide a with that of other porphyrin-related compounds.

The relationship between 1-deoxynojirimycin content and alpha-glucosidase inhibitory activity in leaves of 276 mulberry cultivars (Morus spp.) in Kyoto, Japan.

The relationship between 1-deoxynojirimycin (DNJ) content and alpha-glucosidase inhibitory activity in mulberry (Morus) leaves is discussed. Mulberry leaves were collected from the Center for Bioresource Field Science, Kyoto Institute of Technology, Kyoto, Japan on 19 May, 9 July, and 9 August, 2003. Mulberry leaves were extracted with 75% ethanol. The inhibitory activity for rat intestinal crude enzyme was measured using maltose. The content of DNJ in the extracts was measured using HPLC. The mean DNJ content in the 0.04-0.06% range was high in collected samples. The inhibitory activities in July and August were higher (P < 0.01) than in May, and the activity in July was higher (P < 0.01) than in August. A strong correlation (r = 0.901, r (2) = 0.811, n = 15) existed between DNJ content and alpha-glucosidase inhibition in leaves of Morus bombycis harvested in July. Similarly, correlation coefficients of the other mulberry varieties in July were higher than they were in May or August. The inhibitory activity and the DNJ content of Morus latifolia in August were lower than for any other mulberry variety. These results show that the high inhibitory cultivars harvested in July, except for M. latifolia, are more suited to products that contain high DNJ contents.

Mulberry leaf extract prevents amyloid beta-peptide fibril formation and neurotoxicity.

Mulberry leaf has been reported to possess medicinal properties, including hypoglycemic, hypotensive and diuretic effects. Little is known, however, about its medicinal properties for central nervous system disorders, including Alzheimer's disease. Accumulating evidence suggests that amyloid beta-peptide (1-42) plays an important role in the etiology of Alzheimer's disease. Here we show that mulberry leaf extract inhibits the amyloid beta-peptide (1-42) fibril formation by both the thioflavin T fluorescence assay and atomic force microscopy. Furthermore, mulberry leaf extract protected hippocampal neurons against amyloid beta-peptide (1-42)-induced cell death in a concentration-dependent manner. These results suggest that mulberry leaf extract provides a viable treatment for Alzheimer's disease through the inhibition of amyloid beta-peptide (1-42) fibril formation and attenuation of amyloid beta-peptide (1-42)-induced neurotoxicity.