Derived from the genus maple (Acer), acertannins are a group of gallotannins which have a characteristic 1,5-anhydro-D-glucitol (1,5-AG) occupying the central core position in the tannic acid structure whose hydroxyl groups have one or more galloyl residues. We synthesized all ten naturallyoccurring acertannins and seven new acertannin derivatives from 1,5-AG. Side-by-side comparison revealed that 2,4,6-trigalloyl-1,5-AG (maplexine E : 21) and maplexine F (2,3,6-trigalloyl-1,5-AG : 22) were good inhibitors of ceramidase (CDase). In contrast, the core anhydrosugar 1,5-AG (12) itself and methoxygallate derivatives (23-25) did not show CDase inhibition. Metabolic labeling experiments using NBD-hexanoic acid revealed that 50 µM 6-galloyl-1,5-AG (Ginnalin B : 16), 2,6-digalloyl-1,5-AG (Ginnalin A : 19), and 4,6-digalloyl-1,5-AG (4) increased intracellular NBD-labeled ceramide, by 2.3, 2.2, and 2.1-fold, respectively. It is noteworthy that these acertannins (16, 19, and 4) promoted ceramide synthase 3 (CERS3) gene expression. Acertannins, therefore,represent a new class of potential intracellular ceramide regulators exhibiting both CDase inhibition and ceramide synthase promotion.