Isolation and structural characterization of glycosides from an anti-angiogenic extract of Monnina obtusifolia H.B.K

Abstract

Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is of physiological and pathological importance. Substantial data over the last decade has implicated uncontrolled angiogenesis with various pathological states. Vascular endothelial growth factors (VEGFs) play a critical role in its regulation, and have become one of the most interesting anti-angiogenesis targets. We have investigated the anti-angiogenic potential of plant extracts in a preliminary ELISA screening. The n-BuOH extract obtained from the leaves of Monnina obtusifolia (Polygalaceae) demonstrated an inhibition of VEGF-A or Placental Growth Factor interaction with Flt-1 (VEGF receptor 1), with an inhibition over 50% in particular for VEGF-A/Flt-1 interaction at a concentration of 500 μg/mL. Successively fractionation of the bioactive n-BuOH extracts of M. obtusifolia aerial parts led to the isolation of six new compounds, 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-β-D-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (1), 1-O-(isopentenyl)-6-O-β-D-(4-hydroxy-2-methylene-butanoyl)-glucopyranose (2), 1-O-(4-hydroxy-2-methylene-butanoic acid)-6-O-β-D-(isovaleroyl)-glucopyranose (3), 1-O-(3-methylbut-3enyl)-6-O-β-D-(isovaleroyl)-glucopyranose (4), two new sucrose esters, 3,4-O-β-D-di-feruloyl-fructofuranosyl-6-O-α-D-(p-coumaroyl)-glucopyranoside (5), and 3,4-O-β-D-di-feruloyl-fructofuranosyl-6-O-α-D-(caffeoyl)-glucopyranoside (6), together with known flavonoids. Their structures were established on the basis of detailed spectral analysis. Since none of the isolated compounds showed a relevant inhibition of VEGFs, the biological activity observed for the butanolic extract might be due to the presence of a combination of compounds acting synergistically.