Isolation and structural characterization of glycosides from an anti-angiogenic extract of Monnina obtusifolia H.B.K.
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.
Lepore
Laura
L
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano, SA, Italy.
Malafronte
Nicola
N
Condero
Fausto Bedoya
FB
Gualtieri
Maria J
MJ
Abdo
Susana
S
Dal Piaz
Fabrizio
F
De Tommasi
Nunziatina
N
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004357:Drug Synergism; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves; D029608:Polygalaceae / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D005419:Flavonoids; D006027:Glycosides; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1