Secretion Of Glucagon-Like Peptide-1 Induced By Cynanchum Pregnane Derivatives: Preliminary Hypotheses Regarding Key Structural Elements

In our continued efforts to explore the antidiabetic potential of pregnanes from Apocynaceae, especially from the Asclepiadoideae subfamily, sixteen derivatives 1-16 previously isolated from various Cynanchum species, have been evaluated for their ability to increase glucagon-like peptide-1 (GLP-1) release in a cell assay. As a result, otophylloside A (2), wilfoside C1N (13), and wilfoside C3N (16) were found to stimulate significantly the secretion of GLP-1, doubling the extracellular content of this incretin. Caudatin 3-O-beta-D glucopyranosyl-(1 -> 4)- beta-D-oleandropyranosyl-(1 -> 4)-beta-D-cymaropyranosyl-(1 -> 4)-beta-D-cymaropyranoside (6) was also bioactive, but to a lesser extent (133 % of secretion compared to control cells). This study confirms the potential of certain pregnane derivatives from subfamily Asclepiadoideae to stimulate the release of GLP-1, reduced in patients with type 2 diabetes. In addition, this study outlines some putative structure-activity relationships: the nature of the sugar chain at C-3, as well as the ester moiety at C-12 position appear to be key elements to stimulate GLP-1 secretion.