title: Advanced glycation inhibition and protection against endothelial dysfunction induced by coumarins and procyanidins from Mammea neurophylla.
abstract: Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified.
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Bach Tai
authors.initials: BT
authors.lastname: Dang
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gény
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rouger
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tonnerre
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Gilbertine
authors.initials: G
authors.lastname: Rakolomalala
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Joseph Iharinjaka
authors.initials: JI
authors.lastname: Randriamboavonjy
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Gervaise
authors.initials: G
authors.lastname: Loirand
authors.affiliation: INSERM, U1064, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pacaud
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, Labex LERMIT, Gif sur Yvette Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Richomme
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Séraphin
authors.affiliation: Université d'Angers, SFR QUASAV, EA 921 SONAS, Angers, France. Electronic address: severine.derbre@univ-angers.fr.
authors.forename: Séverine
authors.initials: S
authors.lastname: Derbré
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D042783:Endothelial Cells; D005638:Fruit / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000187:drug effects*; D008297:Male; D031252:Mammea / Q000737:chemistry*; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D044945:Proanthocyanidins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000094062:Betulinic Acid; D000094042:Lupanes
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044946:Biflavonoids; D002392:Catechin; D003374:Coumarins; D017127:Glycation End Products, Advanced; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D044945:Proanthocyanidins; D014315:Triterpenes; D044004:Xanthones; D000094062:Betulinic Acid; C094411:4-phenylcoumarin; C017674:procyanidin; C060796:friedelin; D000094042:Lupanes
keywords: 4-(1-Acetoxypropyl)coumarins; 4-Phenylcoumarins; Advanced glycation end-products (AGEs); Calophyllaceae; Endothelial dysfunction; Mammea neurophylla