Secretion of glucagon-like peptide-1 induced by Cynanchum pregnane derivatives: Preliminary hypotheses regarding key structural elements

Abstract

Listen

Translate article

• First investigation of the GLP-1 secretagogue activity of 16 pregnane derivatives. • Otophylloside A, wilfosides C1N and C3N double GLP-1 secretion in STC-1 cells. • First attempts of structure-GLP-1 secretagogue activity relationships. • The nature of the sugar chain at C-3 and ester moiety at C-12 are key 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 -β-D-glucopyranosyl-(1→4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-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.