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.

Pregnane glycosides from Cynanchum menarandrense

“…All compounds were found to be non-cytotoxic according to the MTS assay, with a cell viability superior to 90%. Regarding the GLP-1 secretagogue effect, none of the compounds stimulated the secretion of GLP-1 in STC-1 cells (values similar to the vehicle), as opposed to the previously assessed 12,20-O-dibenzoyl or 12-Otigloyl 2,6-dideoxyhexose pregnane glycosides [1]. This observation could indicate the necessity of the 12-O acylation and the presence of a dideoxyhexose chain linkage to the pregnane structure to stimulate the secretion of GLP-1.…”

“…The GLP-1 secretion assay was carried out according to the previously published protocol [1]. Briefly, STC-1 cells were cultured in DMEM medium supplemented with 10% FBS, 100 U/mL penicillin, and 100 μg/L streptomycin, at 37°C in 5% CO 2 .…”

“…During a previous search for antidiabetic natural compounds, the ethanolic extract of Cynanchum marnierianum, an endemic Apocynaceae from Madagascar, exhibited significant glucagon-like peptide 1 (GLP-1) secretagogue activity. A bio-guided fractionation was undertaken to isolate the active components, identified as pregnane glycosides [1]. These promising results have prompted us to investigate further Cynanchum species from Madagascar for the same activity.…”

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

“…In this context, we previously discovered that two pregnane glycosides from Cynanchum marnierianum (Apocynaceae), marnieranosides A and B, significantly stimulate GLP-1 secretion of intestinal secretin tumour cells (STC-1) (Tsoukalas et al, 2016). We also demonstrated that P57, a polyhydroxylated pregnane glycoside from Hoodia gordonii, possesses a similar activity in this bioassay.…”

A New Immunosuppressive Pregnane Glycoside and Two Known Analogues from Epigynum cochinchinensis

“…With their unique structural features and significant diverse bioactivities [1], pregnane glycosides have attracted our attention. Immunosuppressive [2], anti-inflammatory [3], anti-epileptic [4], neuroprotective [5], anti-hyperglycemic [6], and cytotoxic [7] activities have been reported for pregnane glycosides, which show great potential as leads in medicine. Epigynum cochinchinensis (Pierre) D.J.…”