Inhibition of intestinal .ALPHA.-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives.

Abstract

Moranoline (1-deoxynojirimycin) isolated from mulberry root bark (Mori Cortex), is a potent intestinal α-glucosidase inhibitor. The IC50 values for sucrase and maltase in various animals ranged around 10-7M. Postprandial hyperglycemia in sucrose-, starch-, or maltose-loaded rats was significantly supressed by simultaneous administration of moranoline in doses over 6 mg/kg. In contrast to the potent inhibition of intestinal α-glucosidase, the inhibition of β-glucosidase, glucoamylase, and α-amylase was weak. Among the N-substituted alkyl derivatives of moranoline, the methyl and ethyl derivatives had more potent hypoglycemic activity than moranoline in sucrose- or starch-loaded rat models. Nojirimycin, or 2, 5-dihydroxymethyl 3, 4-dihydroxypyrrolidine (DMDP), which structurally resembles moranoline, only weakly inhibited α-glucosidase but strongly inhibited β-glucosidase.