Glucose-6-phosphatase and alpha-glucosidase inhibitors from smilax moranensis roots identified by affinity-directed fractionation

Abstract

The ethanol/water-soluble extracts of the roots of Smilax moranensis M. Martens & Galeotti, Smilacaceae, which have been appreciated since pre-Hispanic times and traditionally used to treat type 2 diabetes in Mexico, were fractionated by the applica- tion of the affinity-directed method to identify glucose-6-phosphatase and α-glucosidase inhibitors. Mass spectrometry was used to identify the inhibitor as free ligands after released from the enzymatic complex by denaturing acidic conditions. The affinity study led to the identification of chlorogenic acid as a glucose-6-phosphatase inhibitor, which is the most abundant metabolite present in the analyzed crude drug. In addition, the affinity studies led to the identification of a flavonolignan glycoside as an α- glucosidase inhibitor. In silico analysis with α-glucosidase MAL12 from the yeast Saccharomyces cerevisiae allowed to deter- mine the best conformational rearrangement for the α-glucosidase inhibitors.