title: Inhibition of guinea pig aldehyde oxidase activity by different flavonoid compounds: An in vitro study.
abstract: Aldehyde oxidase (AO), a cytosolic molybdenum-containing hydroxylase, is predominantly active in liver and other tissues of mammalian species and involved in the metabolism of extensive range of aldehydes and nitrogen-containing compounds. A wide range of natural components including polyphenols are able to interfere with AO-catalyzed reactions. Polyphenols and flavonoids are one of the extensive secondary plant metabolites ubiquitously present in plants considered an important part of the human diet. The aim of the present study was to investigate inhibitory effect of selected phenolic compounds from three subclasses of aurone, flavanone and phenolic lactone compounds on the activity of AO, spectrophotometrically. AO enzyme was partially purified from liver of guinea pig. Then, inhibitory effects of 10 flavonoid compounds including 8 derivatives of 2-benzylidenebenzofuran-3(2H)-ones, as well as naringenin and ellagic acid on the activity of aldehyde oxidase were assessed compared with the specific inhibitor of AO, menadione. Among the phenolic compounds with inhibitory effects on the enzyme, ellagic acid (IC50=14.47 μM) was the most potent agent with higher inhibitory action than menadione (IC50=31.84 μM). The mechanisms by which flavonoid compounds inhibit AO activity have been also determined. The inhibitory process of the assessed compounds occurs via either a non-competitive or mixed mode. Although flavonoid compounds extensively present in the nature, mainly in dietary regimen, aurones with promising biological properties are not widely distributed in nature, so synthesis of aurone derivatives is of great importance. Additionally, aurones seem to provide a promising scaffold in medicinal chemistry for the skeleton of new developing drugs, so the results of the current study can be valuable in order to better understanding drug-food as well as drug-drug interaction and also appears to be worthwhile in drug development strategies.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Higher Education Institute of Rab-Rashid, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Siah
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Hosein
authors.initials: MH
authors.lastname: Farzaei
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ashrafi-Kooshk
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Adibi
authors.affiliation: Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Seyed Shahriar
authors.initials: SS
authors.lastname: Arab
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rashidi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: rkhodarahmi@mbrc.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Khodarahmi
mesh_terms: D042931:Aldehyde Oxidase / Q000037:antagonists & inhibitors*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000494:pharmacology; D004610:Ellagic Acid / Q000494:pharmacology; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D008024:Ligands; D008099:Liver / Q000201:enzymology; D008297:Male; D062105:Molecular Docking Simulation
chemical_list: D001572:Benzofurans; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008024:Ligands; D004610:Ellagic Acid; D042931:Aldehyde Oxidase
keywords: Aldehyde oxidase; Aurones; Drug interaction; Flavonoids; Food constituents; Polyphenols