title: Pregnane Glycosides from Cynanchum marnierianum Stimulate GLP-1 Secretion in STC-1 Cells.
abstract: In the framework of the search for natural glucagon-like peptide-1 secretagogues, the bioassay-guided fractionation of the ethanolic extract from Cynanchum marnierianum led to the isolation of two new pregnane glycosides named marnieranosides A (1) and B (2). The structures were determined based on spectroscopic data and were established as 12β,20 S-O-dibenzoyl-pregn-6-en-5α,8β,14β,17β-tetraol-3-O-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranoside (1) and 12β,20R-O-dibenzoyl-pregn-6-en-5α,8β,14β-triol-3-O-β-D-oleandropyranosyl-(1 → 4)-β-D-canaropyranosyl-(1 → 4)-β-D-cymaropyranoside (2). They present structural analogies to pregnanes previously described in species known for their appetite suppressant and antihyperglycemic effects, such as P57 from Hoodia gordonii. Lupeol (3), a known dipeptidyl peptidase-4 inhibitor, and the insulinomimetic kaempferol-3-O-neohesperidoside (4) were also identified in C. marnierianum. In an in vitro assay on secretin tumor cell line-1 cells, compounds 1, 2, and P57 were found to stimulate the secretion of GLP-1 by 130 % (all tested at 100 µM). These results suggest that C. marnierianum could be of great interest in the treatment of type 2 diabetes, and that pregnane derivatives should be partly responsible via the stimulation of glucagon-like peptide-1 secretion.
authors.affiliation: Laboratory of Pharmacognosy and Bioactive Natural Products, UMR 7200, University of Strasbourg, Illkirch Graffenstaden, France.
authors.forename: Michail
authors.initials: M
authors.lastname: Tsoukalas
authors.affiliation: Laboratory of Pharmacognosy and Bioactive Natural Products, UMR 7200, University of Strasbourg, Illkirch Graffenstaden, France.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Muller
authors.affiliation: Laboratory of Pharmacognosy and Bioactive Natural Products, UMR 7200, University of Strasbourg, Illkirch Graffenstaden, France.
authors.forename: Annelise
authors.initials: A
authors.lastname: Lobstein
authors.affiliation: Laboratory of Pharmacognosy and Bioactive Natural Products, UMR 7200, University of Strasbourg, Illkirch Graffenstaden, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Urbain
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D031105:Cynanchum / Q000737:chemistry*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006027:Glycosides / Q000302:isolation & purification* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D011278:Pregnanes / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D006027:Glycosides; D007004:Hypoglycemic Agents; D011278:Pregnanes; C574437:pregnane glycoside; D052216:Glucagon-Like Peptide 1