Screening of inhibitors of porcine dipeptidyl peptidase IV activity in aqueous extracts from marine organisms

Dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) hydrolyses biologically active peptides that control critical functions. For example, action of glucagons-like peptide 1, an hormone that plays multiple roles in metabolic homeostasis and a potential agent for the treatment of type 2 diabetes mellitus is diminished by its susceptibility to DPPIV activity. The goal of this work was to the search for DPPIV inhibitory activity in the Caribbean marine fauna. The screening was done in aqueous crude extracts of species belonging to phyla Cnidaria, Mollusca, Annelida, Echinodermata, Poriphera, Chordata, Chlorophycota and Chlorophyta collected on the Northern coast of Havana (Cuba). An inhibitory activity was found in extracts of three species belonging to phyla Poriphera and Cnidaria: the sponge Xetospongia muta and the sea anemones Bunodosoma granulifera and Bartholomea annulata. The crude extracts from these species were treated with 2.5% final concentration of trichloroacetic acid (TCA) or with heat (60 degrees C, 10 min). Both treatments increased inhibitory activity in X. muta but failed in B. granulifera and B. annulata extracts. Preliminary characterization indicated that in each case the effect on DPPIV activity is dose-dependent, the inhibition is slow and the molecule responsible for DPPIV inhibition has a low molecular weight. The present contribution shows that the detected species are promising sources of DPPIV natural inhibitors with potential therapeutic applications (c) 2006 Elsevier Inc. All rights reserved.