Pregnane Glycosides from Cynanchum marnierianum Stimulate GLP-1 Secretion in STC-1 Cells

摘要

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 12 beta,20 S-O-dibenzoyl-pregn-6-en-5 alpha,8 beta,14 beta,17 beta-tetraol-3-O-beta-D-oleandropyranosyl-(1 -> 4)-beta-D-cymaropyranoside (1) and 12 beta,20R-O-dibenzoyl-pregn-6-en-5 alpha,8 beta,14 beta-triol-3-O-beta-D-oleandropyranosyl-(1 -> 4)-beta-D-canaropyranosyl-(1 -> 4)-beta-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 mu M). 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.