title: Evaluation of aldose reductase inhibition and docking studies of some secondary metabolites, isolated from Origanum vulgare L. ssp. hirtum.
abstract: Five polar constituents of Origanum vulgare L. ssp. hirtum were investigated for their ability to inhibit aldose reductase (ALR2), the first enzyme of the polyol pathway implicated in the secondary complications of diabetes. The most active compound was found to be lithospermic acid B. Caffeic acid was inactive as it showed no inhibitory activity against the enzyme. The order of the inhibitory activity of the remaining compounds was: rosmarinic acid >12-hydroxyjasmonic acid 12-O-beta-glucopyranoside > p-menth-3-ene-1,2-diol 1-O-beta-glucopyranoside. Docking studies have been undertaken to gain insight into the binding mode of the investigated compounds at the active site of ALR2. The predicted hydrogen bonding and hydrophobic interactions may explain the observed inhibitory activity.
authors.affiliation: Department of Pharmacognosy and Chemistry of Natural Products, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Greece. koukoulitsa@pharm.uoa.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Koukoulitsa
authors.forename: Chariklia
authors.initials: C
authors.lastname: Zika
authors.forename: George D
authors.initials: GD
authors.lastname: Geromichalos
authors.forename: Vassilis J
authors.initials: VJ
authors.lastname: Demopoulos
authors.forename: Helen
authors.initials: H
authors.lastname: Skaltsa
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002934:Cinnamates / Q000494:pharmacology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D053630:Depsides; D003920:Diabetes Mellitus / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism; D031341:Origanum / Q000737:chemistry*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D000097123:Rosmarinic Acid
chemical_list: D000449:Aldehyde Reductase; D002934:Cinnamates; D053630:Depsides; D004791:Enzyme Inhibitors; D005960:Glucosides; D009249:NADP; D000097123:Rosmarinic Acid